Unmutated Immunoglobulin M Can Protect Mice from Death by Influenza Virus Infection

To elucidate the role of class switch recombination (CSR) and somatic hypermutation (SHM) in virus infection, we have investigated the influence of the primary and secondary infections of influenza virus on mice deficient of activation-induced cytidine deaminase (AID), which is absolutely required for CSR and SHM. In the primary infection, AID deficiency caused no significant difference in mortality but did cause difference in morbidity. In the secondary infection with a lethal dose of influenza virus, both AID−/− and AID+/− mice survived completely. However, AID−/− mice could not completely block replication of the virus and their body weights decreased severely whereas AID+/− mice showed almost complete prevention from the reinfection. Depletion of CD8+ T cells by administration of an anti-CD8 monoclonal antibody caused slightly severer body weight loss but did not alter the survival rate of AID−/− mice in secondary infection. These results indicate that unmutated immunoglobulin (Ig)M alone is capable of protecting mice from death upon primary and secondary infections. Because the titers of virus-neutralizing antibodies were comparable between AID−/− and AID+/− mice at the time of the secondary infection, a defect of AID−/− mice in protection of morbidity might be due to the absence of either other Ig classes such as IgG, high affinity antibodies with SHM, or both

Variable Selection in Nonlinear Principal Component Analysis

Principal components analysis (PCA) is a popular dimension reduction method and is applied to analyze quantitative data. For PCA to qualitative data, nonlinear PCA can be applied, where the data are quantified by using optimal scaling that nonlinearly transforms qualitative data into quantitative data. Then nonlinear PCA reveals nonlinear relationships among variables with different measurement levels. Using this quantification, we can consider variable selection in the context of PCA for qualitative data. In PCA for quantitative data, modified PCA (M.PCA) of Tanaka and Mori derives principal components which are computed as a linear combination of a subset of variables but can reproduce all the variables very well. This means that M.PCA can select a reasonable subset of variables with different measurement levels if it is extended so as to deal with qualitative data by using the idea of nonlinear PCA. A nonlinear M.PCA is therefore proposed for variable selection in nonlinear PCA. The method, in this chapter, is based on the idea in “Nonlinear Principal Component Analysis and its Applications” by Mori et al. (Springer). The performance of the method is evaluated in a numerical example

Anatomical variation of the Psoas Valley: a scoping review

Abstract: Background: This scoping review aimed to investigate the literature on the anatomy of the psoas valley, an anterior depression on the acetabular rim, and propose a unified definition of the anatomical structure, describe its dimensions, anatomical variations and clinical implications. Methods: A systematic computer search of EMBASE, PubMed and Cochrane for literature related to the psoas valley was undertaken using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Clinical outcome studies, prospective/retrospective case series, case reports and review articles that described the psoas valley and its synonyms were included. Studies on animals as well as book chapters were excluded. Results: Of the 313 articles, the filtered literature search identified 14 papers describing the psoas valley and its synonyms such as iliopsoas notch, a notch between anterior inferior iliac spine and the iliopubic eminence, Psoas-U and anterior wall depression. Most of these were cross-sectional studies that mainly analyzed normal skeletal hips. In terms of anatomical variation, 4 different configurations of the anterior acetabular rim have been identified and it was found that the curved type was the most frequent while the straight type may be nonexistent. Additionally, the psoas valley tended to be deeper in males as compared with females. Several papers established the psoas valley, or Psoas-U in a consistent location at approximately 3 o’clock on the acetabular rim which may have implications with labral pathology. Conclusion: This review highlights the importance of the anatomy of the psoas valley which is a consistent bony landmark. The anatomy and the anatomical variations of the psoas valley need to be well-appreciated by surgeons involved in the management of young adults with hip pathology and also joint replacement surgeons to ensure appropriate seating of the acetabular component

Prediction and validation of a mechanism to control the threshold for inhibitory synaptic plasticity

Synaptic plasticity, neuronal activity-dependent sustained alteration of the efficacy of synaptic transmission, underlies learning and memory. Activation of positive-feedback signaling pathways by an increase in intracellular Ca2+ concentration ([Ca2+]i) has been implicated in synaptic plasticity. However, the mechanism that determines the [Ca2+]i threshold for inducing synaptic plasticity is elusive. Here, we developed a kinetic simulation model of inhibitory synaptic plasticity in the cerebellum, and systematically analyzed the behavior of intricate molecular networks composed of protein kinases, phosphatases, etc. The simulation showed that Ca2+/calmodulin-dependent protein kinase II (CaMKII), which is essential for the induction of synaptic plasticity, was persistently activated or suppressed in response to different combinations of stimuli. The sustained CaMKII activation depended on synergistic actions of two positive-feedback reactions, CaMKII autophosphorylation and CaMKII-mediated inhibition of a CaM-dependent phosphodiesterase, PDE1. The simulation predicted that PDE1-mediated feedforward inhibition of CaMKII predominantly controls the Ca2+ threshold, which was confirmed by electrophysiological experiments in primary cerebellar cultures. Thus, combined application of simulation and experiments revealed that the Ca2+ threshold for the cerebellar inhibitory synaptic plasticity is primarily determined by PDE1

重症低血糖後の急性冠症候群の絶対リスク : 日本のナショナルデータベースを用いた一般集団対象の2年間のコホート研究

Aims/introduction: Although the epidemiological relationship between hypoglycemia and increased risk of acute coronary syndrome (ACS) has been well established, the time period for increased risk of ACS after a severe hypoglycemic episode remains unknown. The present study aimed to determine the ACS risk after a severe hypoglycemic episode. Materials and methods: We carried out a retrospective population-based cohort study based on national claims data in Japan. We retrieved data of diabetes patients aged ≥35 years collected from April 2014 to March 2016. The absolute risk of ACS was defined as the occurrence of an emergency percutaneous coronary intervention after a severe hypoglycemic episode. Results: In total, data of 7,909,626 patients were included in the analysis. The absolute risk of ACS was 2.9 out of 1,000 person-years in all patients. ACS risk in patients with severe hypoglycemic episodes was 3.0 out of 1,000 person-years. Severe hypoglycemic episodes increased the absolute risk of ACS in patients aged ≥70 years, but not in patients aged <70 years. The absolute risk of ACS was 10.6 out of 1,000 person-years within 10 days of a severe hypoglycemic episode. There was a significant trend between shorter duration after an episode and higher ACS risk. Conclusions: Severe hypoglycemia was associated with an increased risk of ACS in elderly diabetes patients. ACS risk increased with a shorter period after a severe hypoglycemic episode, suggesting that severe hypoglycemia leads to an increased risk of ACS in diabetes patients. These findings show that it is important to avoid severe hypoglycemia while treating diabetes, particularly in elderly patients.博士（医学）・甲第732号・令和2年3月16日© 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License(https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made

Tooth movement into the maxillary sinus

Objectives: To evaluate the effect of overloading on the palatal movement of the maxillary molar. Materials and methods: The maxillary first molar of male C57Bl/6 mice was moved palatally with 10-g or 30-g load for 14 days, and amount of tooth movement was longitudinally measured on micro-computed tomography images (each group, N=5). Bone remodeling around the molar root under the 30-g load was evaluated at days 3, 5, 7, and 14 after the starting of tooth movement using histomorphometry and immunodetection of bone-restricted Ifitm (interferon inducible transmembrane)-like protein, a novel marker of active bone formation (each group, N=5). Result: In the 10-g load group, the amount of tooth movement increased dramatically between day 5 to day 7, and gradually increased thereafter. In 30-g load group, tooth movement at day 5 and day 7 was significantly lower than those in the 10-g load group; however, total tooth movement for 14 days was similar in both groups. Orthodontic load of 30-g stimulated bone formation on the sinus wall, but bone resorption on the periodontal ligament side was delayed because of the hyalinization, which means strong force application was not accelerate tooth movement. Moreover, some root resorption was induced under the excessive force application. Conclusion: Root penetration into sinus and bone height reduction does not occur because new bone formation on the maxillary sinus is induced prior to bone resorption on the periodontal side, even though excessive orthodontic force is applied. However, excessive force is subject to induce root resorption

The Usefulness of Readout-Segmented Echo-Planar Imaging (RESOLVE) for Bio-phantom Imaging Using 3-Tesla Clinical MRI

Readout-segmented echo-planar imaging (RESOLVE) is a multi-shot echo-planar imaging (EPI) modality with k-space segmented in the readout direction. We investigated whether RESOLVE decreases the distortion and artifact in the phase direction and increases the signal-to-noise ratio (SNR) in phantoms image taken with 3-tesla (3T) MRI versus conventional EPI. We used a physiological saline phantom and subtraction mapping and observed that RESOLVE’s SNR was higher than EPI’s. Using RESOLVE, the combination of a special-purpose coil and a large-loop coil had a higher SNR compared to using only a head/neck coil. RESOLVE’s image distortioas less than EPI’s. We used a 120 mM polyethylene glycol phantom to examine the phase direction artifact.vThe range where the artifact appeared in the apparent diffusion coefficient (ADC) image was shorter with RESOLVE compared to EPI. We used RESOLVE to take images of a Jurkat cell bio-phantom: the cell-region ADC was 856×10−6mm2/sec and the surrounding physiological saline-region ADC was 2,951×10−6mm2/sec. The combination of RESOLVE and the 3T clinical MRI device reduced image distortion and improved SNR and the identification of accurate ADC values due to the phase direction artifact reduction. This combination is useful for obtaining accurate ADC values of bio-phantoms