Publications by authors named "Michio Suzuki"

280 Publications

Reduced cortical thickness of the paracentral lobule in at-risk mental state individuals with poor 1-year functional outcomes.

Transl Psychiatry 2021 Jul 14;11(1):396. Epub 2021 Jul 14.

Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.

Although widespread cortical thinning centered on the fronto-temporal regions in schizophrenia has been reported, the findings in at-risk mental state (ARMS) patients have been inconsistent. In addition, it remains unclear whether abnormalities of cortical thickness (CT) in ARMS individuals, if present, are related to their functional decline irrespective of future psychosis onset. In this multicenter study in Japan, T1-weighted magnetic resonance imaging was performed at baseline in 107 individuals with ARMS, who were subdivided into resilient (77, good functional outcome) and non-resilient (13, poor functional outcome) groups based on the change in Global Assessment of Functioning scores during 1-year follow-up, and 104 age- and sex-matched healthy controls recruited at four scanning sites. We measured the CT of the entire cortex and performed group comparisons using FreeSurfer software. The relationship between the CT and cognitive functioning was examined in an ARMS subsample (n = 70). ARMS individuals as a whole relative to healthy controls exhibited a significantly reduced CT, predominantly in the fronto-temporal regions, which was partly associated with cognitive impairments, and an increased CT in the left parietal and right occipital regions. Compared with resilient ARMS individuals, non-resilient ARMS individuals exhibited a significantly reduced CT of the right paracentral lobule. These findings suggest that ARMS individuals partly share CT abnormalities with patients with overt schizophrenia, potentially representing general vulnerability to psychopathology, and also support the role of cortical thinning in the paracentral lobule as a predictive biomarker for short-term functional decline in the ARMS population.
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http://dx.doi.org/10.1038/s41398-021-01516-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289863PMC
July 2021

Pediatric sepsis cases diagnosed with group B streptococcal meningitis using next-generation sequencing: a report of two cases.

BMC Infect Dis 2021 Jun 5;21(1):531. Epub 2021 Jun 5.

Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: Group B Streptococcus (GBS) is an important cause of invasive infection in neonates and infants. Cerebrospinal fluid (CSF) findings and culture may not show evidence of infection early in GBS meningitis. Next-generation sequencing (NGS) has the potential to detect microbial genetic material in patients with infectious diseases. We report two cases of infantile sepsis of GBS meningitis with negative results for CSF culture tests, but positive results for NGS analysis.

Case Presentation: Patient 1 was a 22-day-old male infant diagnosed with sepsis and meningitis. His CSF findings showed pleocytosis, decreased glucose, and increased protein levels. However, CSF and blood culture results at admission were negative. He received a total of 3 weeks of treatment with ampicillin and cefotaxime, and showed clinical improvement. GBS was detected through NGS analysis of CSF collected at admission. Patient 2 was a 51-day-old male infant with sepsis. CSF findings on admission were normal, and blood and CSF cultures were also negative. Intravenous ampicillin and cefotaxime treatment were initiated. Treatment was de-escalated to ampicillin alone because Enterococcus faecalis was cultured from urine. He was discharged after a total of 1 week of antibiotic treatment. Six days after discharge, he was re-hospitalized for sepsis. Blood and CSF cultures were negative, and E. faecalis was again cultured from urine. He received a total of 3 weeks of ampicillin treatment for enterococcal-induced nephritis and did not relapse thereafter. NGS pathogen searches were retrospectively performed on both blood and CSF collected at the first and second admission. GBS was detected in the CSF collected at the first admission, but no significant pathogen was detected in the other samples. Inadequate treatment for GBS meningitis at the first admission may have caused the recurrence of the disease.

Conclusion: Infantile sepsis may present bacterial meningitis that is not diagnosed by either culture testing or CSF findings. NGS analysis for CSF may be useful for confirming the diagnosis of bacterial meningitis.
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http://dx.doi.org/10.1186/s12879-021-06231-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180162PMC
June 2021

Identification and functional analysis of cadmium-binding protein in the visceral mass of Crassostrea gigas.

Sci Rep 2021 May 28;11(1):11306. Epub 2021 May 28.

Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.

The Pacific oyster, Crassostrea gigas, is a traditional food worldwide. The soft body of the oyster can easily accumulate heavy metals such as cadmium (Cd). To clarify the molecular mechanism of Cd accumulation in the viscera of C. gigas, we identified Cd-binding proteins. 5,10,15,20-Tetraphenyl-21H,23H-porphinetetrasulfonic acid, disulfuric acid, tetrahydrate, and Cd-binding competition experiments using immobilized metal ion affinity chromatography revealed the binding of water-soluble high molecular weight proteins to Cd, including C. gigas protein disulfide isomerase (cgPDI). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses revealed two CGHC motifs in cgPDI. The binding between Cd and rcgPDI was confirmed through a Cd-binding experiment using the TPPS method. Isothermal titration calorimetry (ITC) revealed the binding of two Cd ions to one molecule of rcgPDI. Circular dichroism (CD) spectrum and tryptophan fluorescence analyses demonstrated that the rcgPDI bound to Cd. The binding markedly changed the two-dimensional or three-dimensional structures. The activity of rcgPDI measured by a PDI Activity Assay Kit was more affected by the addition of Cd than by human PDI. Immunological analyses indicated that C. gigas contained cgPDI at a concentration of 1.0 nmol/g (viscera wet weight). The combination of ITC and quantification results revealed that Cd-binding to cgPDI accounted for 20% of the total bound Cd in the visceral mass. The findings provide new insights into the defense mechanisms of invertebrates against Cd.
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http://dx.doi.org/10.1038/s41598-021-90882-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163822PMC
May 2021

Association between marital status and cognitive function in Japan: results from the Toyama Dementia Survey.

Psychogeriatrics 2021 Jul 25;21(4):627-635. Epub 2021 May 25.

Department of Neuropsychiatry, School of Medicine, University of Toyama, Toyama, Japan.

Background: This study aims to clarify the association between marital status and dementia in Japan, adjusting for socioeconomic, lifestyle, and lifestyle-related disease factors.

Methods: Data from the Japanese Toyama Dementia Survey were used. Individuals aged ≥65 years living in Toyama Prefecture were randomly selected, and 1171 participants were analysed, with a sampling rate of 0.5%. The participants' marital status, socioeconomic status, lifestyle factors, and lifestyle-related diseases were assessed. The odds ratio (OR) of marital status for each lifestyle factor and medical histories were calculated by logistic regression analysis. The OR of marital status for dementia was also calculated by logistic regression analysis.

Results: The prevalence of dementia was 7.4% for married, and 20.6% for non-married participants. Non-married participants showed a higher prevalence of a history of stroke than married participants. The age- and sex-adjusted OR of marital status for dementia was 1.99 (95% confidence interval (CI) 1.24-3.18) for non-married compared with married participants. Following variable adjustments, the OR for dementia was higher for non-married participants (adjusted OR 1.71; 95% CI 1.03-2.85).

Conclusions: Non-marital status was an independent risk factor for dementia in Japan even after adjusting for socioeconomic, lifestyle, and lifestyle-related disease factors. Non-married people were more likely to have dementia because of their history of stroke.
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http://dx.doi.org/10.1111/psyg.12724DOI Listing
July 2021

Heschl's Gyrus Duplication Pattern in Individuals at Risk of Developing Psychosis and Patients With Schizophrenia.

Front Behav Neurosci 2021 20;15:647069. Epub 2021 Apr 20.

Department of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.

An increased prevalence of duplicated Heschl's gyrus (HG), which may reflect an early neurodevelopmental pathology, has been reported in schizophrenia (Sz). However, it currently remains unclear whether individuals at risk of psychosis exhibit similar brain morphological characteristics. This magnetic resonance imaging study investigated the distribution of HG gyrification patterns [i.e., single HG, common stem duplication (CSD), and complete posterior duplication (CPD)] and their relationship with clinical characteristics in 57 individuals with an at-risk mental state (ARMS) [of whom 5 (8.8%) later developed Sz], 63 patients with Sz, and 61 healthy comparisons. The prevalence of duplicated HG patterns (i.e., CSD or CPD) bilaterally was significantly higher in the ARMS and Sz groups than in the controls, whereas no significant differences were observed in HG patterns between these groups. The left CSD pattern, particularly in the Sz group, was associated with a verbal fluency deficit. In the ARMS group, left CSD pattern was related to a more severe general psychopathology. The present results suggest that an altered gyrification pattern on the superior temporal plane reflects vulnerability factors associated with Sz, which may also contribute to the clinical features of high-risk individuals, even without the onset of psychosis.
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http://dx.doi.org/10.3389/fnbeh.2021.647069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093503PMC
April 2021

Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis.

JAMA Psychiatry 2021 Jul;78(7):753-766

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.

Importance: The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk.

Objective: To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-).

Design, Setting, And Participants: In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020.

Main Outcomes And Measures: Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group).

Results: Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001).

Conclusions And Relevance: This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.
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http://dx.doi.org/10.1001/jamapsychiatry.2021.0638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100913PMC
July 2021

Prolonged P300 Latency in Antipsychotic-Free Subjects with At-Risk Mental States Who Later Developed Schizophrenia.

J Pers Med 2021 Apr 21;11(5). Epub 2021 Apr 21.

Department of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.

We measured P300, an event-related potential, in subjects with at-risk mental states (ARMS) and aimed to determine whether P300 parameter can predict progression to overt schizophrenia. Thirty-three subjects with ARMS, 39 with schizophrenia, and 28 healthy controls participated in the study. All subjects were antipsychotic-free. Subjects with ARMS were followed-up for more than two years. Cognitive function was measured by the Brief assessment of Cognition in Schizophrenia (BACS) and Schizophrenia Cognition Rating Scale (SCoRS), while the modified Global Assessment of Functioning (mGAF) was used to assess global function. Patients with schizophrenia showed smaller P300 amplitudes and prolonged latency at Pz compared to those of healthy controls and subjects with ARMS. During the follow-up period, eight out of 33 subjects with ARMS developed overt psychosis (ARMS-P) while 25 did not (ARMS-NP). P300 latency of ARMS-P was significantly longer than that of ARMS-NP. At baseline, ARMS-P elicited worse cognitive functions, as measured by the BACS and SCoRS compared to ARMS-NP. We also detected a significant relationship between P300 amplitudes and mGAF scores in ARMS subjects. Our results suggest the usefulness of prolonged P300 latency and cognitive impairment as a predictive marker of later development of schizophrenia in vulnerable individuals.
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http://dx.doi.org/10.3390/jpm11050327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143351PMC
April 2021

Functional analyses of chitinolytic enzymes in the formation of calcite prisms in Pinctada fucata.

Micron 2021 Jun 7;145:103063. Epub 2021 Apr 7.

Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan. Electronic address:

The mollusk shells present distinctive microstructures that are formed by small amounts of organic matrices controlling the crystal growth of calcium carbonate. The shell of Pinctada fucata has the prismatic layer consisting of prisms of single calcite crystals and the nacreous layer consisting of aragonite tablets. The calcite crystal of prisms contains small angle grain boundaries caused by a dense intracrystalline organic matrix network to improve mechanical strength. Previously, we identified chitin and chitinolytic enzymes as components of this intracrystalline organic matrix. In this study, to reveal the function of those organic matrices in calcium carbonate crystallization, calcites synthesized in chitin gel with or without chitinolytic enzymes were analyzed by using transmission electron microscope (TEM) and atom probe tomography (APT), showing ion clusters derived from chitin inside of a calcite and small angle grain boundaries at optimal chitinolytic concentration. Furthermore, we performed the experiment in which chitinase inhibitor was injected into a living P. fucata. Nanoindentation and electron back scattered diffraction (EBSD) show that mechanical properties and crystal orientation were changed. These results suggested that chitinolytic enzymes work cooperatively with chitin to regulate the crystal growth and mechanical properties of the prismatic layer.
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http://dx.doi.org/10.1016/j.micron.2021.103063DOI Listing
June 2021

Reduced Hippocampal Subfield Volume in Schizophrenia and Clinical High-Risk State for Psychosis.

Front Psychiatry 2021 22;12:642048. Epub 2021 Mar 22.

Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.

Magnetic resonance imaging (MRI) studies in schizophrenia demonstrated volume reduction in hippocampal subfields divided on the basis of specific cytoarchitecture and function. However, it remains unclear whether this abnormality exists prior to the onset of psychosis and differs across illness stages. MRI (3 T) scans were obtained from 77 patients with schizophrenia, including 24 recent-onset and 40 chronic patients, 51 individuals with an at-risk mental state (ARMS) (of whom 5 subsequently developed psychosis within the follow-up period), and 87 healthy controls. Using FreeSurfer software, hippocampal subfield volumes were measured and compared across the groups. Both schizophrenia and ARMS groups exhibited significantly smaller volumes for the bilateral Cornu Ammonis 1 area, left hippocampal tail, and right molecular layer of the hippocampus than the healthy control group. Within the schizophrenia group, chronic patients exhibited a significantly smaller volume for the left hippocampal tail than recent-onset patients. The left hippocampal tail volume was positively correlated with onset age, and negatively correlated with duration of psychosis and duration of medication in the schizophrenia group. Reduced hippocampal subfield volumes observed in both schizophrenia and ARMS groups may represent a common biotype associated with psychosis vulnerability. Volumetric changes of the left hippocampal tail may also suggest ongoing atrophy after the onset of schizophrenia.
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http://dx.doi.org/10.3389/fpsyt.2021.642048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019805PMC
March 2021

Iron Elution from Iron and Steel Slag Using Bacterial Complex Identified from the Seawater.

Materials (Basel) 2021 Mar 17;14(6). Epub 2021 Mar 17.

Department of Applied Biological Chemistry, Graduate School of Agriculture, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657, Japan.

Iron and steel slag (ISS) is a byproduct of iron refining processes. The lack of iron in seawater can cause barren grounds where algae cannot grow. To improve the barren grounds of the sea, a supply of iron to the seawater is necessary. This study focused on bacteria interacting with ISS and promoting iron elution in seawater. sp. (TO1A) and sp. (TO1B) were isolated from Tokyo Bay and Sagami Bay. The co-culture of both bacteria promoted more iron elution than individual cultures. After the incubation of both bacteria with ISS, quartz and vaterite appeared on the surface of the ISS. To maintain continuous iron elution from the ISS in the seawater, we also isolated sp. (TO7) that formed a yellow biofilm on the ISS. Iron was eluted by TO1A and TO1B, and biofilm was synthesized by TO7 continuously in the seawater. The present research is expected to contribute to the improvement of ISS usage as a material for the construction of seaweed forests.
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http://dx.doi.org/10.3390/ma14061477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002712PMC
March 2021

Facial nerve palsy with acute otitis media associated with EB virus infection.

Pediatr Int 2021 May 25;63(5):599-600. Epub 2021 Mar 25.

Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.

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http://dx.doi.org/10.1111/ped.14451DOI Listing
May 2021

Anomalous brain gyrification patterns in major psychiatric disorders: a systematic review and transdiagnostic integration.

Transl Psychiatry 2021 03 17;11(1):176. Epub 2021 Mar 17.

Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.

Anomalous patterns of brain gyrification have been reported in major psychiatric disorders, presumably reflecting their neurodevelopmental pathology. However, previous reports presented conflicting results of patients having hyper-, hypo-, or normal gyrification patterns and lacking in transdiagnostic consideration. In this article, we systematically review previous magnetic resonance imaging studies of brain gyrification in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder at varying illness stages, highlighting the gyral pattern trajectory for each disorder. Patients with each psychiatric disorder may exhibit deviated primary gyri formation under neurodevelopmental genetic control in their fetal life and infancy, and then exhibit higher-order gyral changes due to mechanical stress from active brain changes (e.g., progressive reduction of gray matter volume and white matter integrity) thereafter, representing diversely altered pattern trajectories from those of healthy controls. Based on the patterns of local connectivity and changes in neurodevelopmental gene expression in major psychiatric disorders, we propose an overarching model that spans the diagnoses to explain how deviated gyral pattern trajectories map onto clinical manifestations (e.g., psychosis, mood dysregulation, and cognitive impairments), focusing on the common and distinct gyral pattern changes across the disorders in addition to their correlations with specific clinical features. This comprehensive understanding of the role of brain gyrification pattern on the pathophysiology may help to optimize the prediction and diagnosis of psychiatric disorders using objective biomarkers, as well as provide a novel nosology informed by neural circuits beyond the current descriptive diagnostics.
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http://dx.doi.org/10.1038/s41398-021-01297-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969935PMC
March 2021

Microstructure and mineral components of the outer dentin of Chimaera phantasma tooth plates.

Anat Rec (Hoboken) 2021 Feb 23. Epub 2021 Feb 23.

Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.

Tooth plates are a unique dental organ found in holocephalan fishes and lungfish. The chimaeroid tooth plates are atypical in terms of biomineralization, due to the hard tissue composition of whitlockite and apatite, while those of lungfish and other vertebrates are composed of apatite. The tooth plates are overlaid by a thin veneer-outer dentin-whose composition and role are not known. We aimed to test whether the outer dentin is composed of whitlockite or apatite, and whether it protects the osteodentin from abrasion and supports its overall strength. For this purpose, the mineral components and microstructure of outer dentin were studied. Our analyses of the outer dentin from the anterior (vomerine) tooth plates of Chimaera phantasma revealed that the mineral component is magnesium- and carbonate-containing calcium-deficient apatite and that the outer dentin has a three-zone structure. The main body is sandwiched between thin zones, which are less mineralized than the main body. Furthermore, in the outer zone and the main body, a higher-order structure was formed in accordance with the organization of wide and narrow fibers. Mineralization made the main body a composite of bundles of fibers and apatite. Transmission electron microscopy showed a structural relationship between apatite and the fibrous component on which the apatite was formed. Such a structure of the main body could be highly effective as a framework to resist abrasion and support the overall strength of the tooth plate.
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http://dx.doi.org/10.1002/ar.24606DOI Listing
February 2021

Quercetin 3,5,7,3',4'-pentamethyl ether from Kaempferia parviflora directly and effectively activates human SIRT1.

Commun Biol 2021 02 19;4(1):209. Epub 2021 Feb 19.

Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Sirtuin 1 (SIRT1), an NAD-dependent deacetylase, is a crucial regulator that produces multiple physiological benefits, such as the prevention of cancer and age-related diseases. SIRT1 is activated by sirtuin-activating compounds (STACs). Here, we report that quercetin 3,5,7,3',4'-pentamethyl ether (KPMF-8), a natural STAC from Thai black ginger Kaempferia parviflora, interacts with SIRT1 directly and stimulates SIRT1 activity by enhancing the binding affinity of SIRT1 with Ac-p53 peptide, a native substrate peptide without a fluorogenic moiety. The binding affinity between SIRT1 and Ac-p53 peptide was enhanced 8.2-fold by KPMF-8 but only 1.4-fold by resveratrol. The specific binding sites of KPMF-8 to SIRT1 were mainly localized to the helix2-turn-helix3 motif in the N-terminal domain of SIRT1. Intracellular deacetylase activity in MCF-7 cells was promoted 1.7-fold by KPMF-8 supplemented in the cell medium but only 1.2-fold by resveratrol. This work reveals that KPMF-8 activates SIRT1 more effectively than resveratrol does.
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http://dx.doi.org/10.1038/s42003-021-01705-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896056PMC
February 2021

Increased Heschl's Gyrus Duplication in Schizophrenia Spectrum Disorders: A Cross-Sectional MRI Study.

J Pers Med 2021 Jan 12;11(1). Epub 2021 Jan 12.

Department of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.

Duplicated Heschl's gyrus (HG) is prevalent in patients with schizophrenia and may reflect early neurodevelopmental anomalies. However, it currently remains unclear whether patients with schizotypal disorder, a prototypic disorder within the schizophrenia spectrum, exhibit a similar HG gyrification pattern. In this magnetic resonance imaging study, HG gyrification patterns were examined in 47 patients with schizotypal disorder, 111 with schizophrenia, and 88 age- and sex-matched healthy subjects. HG gyrification patterns were classified as single, common stem duplication (CSD), or complete posterior duplication (CPD). The prevalence of the duplicated HG patterns (CSD or CPD) bilaterally was higher in the schizophrenia and schizotypal groups than in healthy controls, whereas no significant difference was observed between the schizophrenia and schizotypal groups. Schizophrenia patients with the right CPD pattern had less severe positive symptoms, whereas the right single HG pattern was associated with higher doses of antipsychotic medication in schizotypal patients. The present study demonstrated shared HG gyrification patterns in schizophrenia spectrum disorders, which may reflect a common biological vulnerability factor. HG patterns may also be associated with susceptibility to psychopathology.
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http://dx.doi.org/10.3390/jpm11010040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828168PMC
January 2021

Features of Duration Mismatch Negativity Around the Onset of Overt Psychotic Disorders: A Longitudinal Study.

Cereb Cortex 2021 Mar;31(5):2416-2424

Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, 930-0194, Japan.

Reduced amplitude of duration mismatch negativity (dMMN) has been reported in psychotic disorders and at-risk mental state (ARMS); however, few longitudinal MMN studies have examined the amplitude changes during the course of psychosis. We compared dMMN amplitude between ARMS individuals with later psychosis onset and those without, and we longitudinally examined potential dMMN changes around psychosis onset. Thirty-nine ARMS subjects and 22 healthy controls participated in this study. Of the 39 ARMS subjects, 11 transitioned to psychosis (at-risk mental state with later psychosis onset [ARMS-P]) during follow-up and 28 did not (at-risk mental state without later psychosis onset [ARMS-NP]). dMMN was measured twice using an auditory oddball paradigm with a mean interval of 2 years. Follow-up dMMN data were available for all but four ARMS-P subjects. dMMN amplitude at baseline was smaller in ARMS-P subjects compared with control and ARMS-NP subjects. Additionally, ARMS-P subjects displayed a longitudinal decline in dMMN amplitude, which was not present in control and ARMS-P subjects. We also observed a progressive decline in dMMN amplitude during the transition period, suggesting dynamic brain changes associated with the psychosis onset. Our findings implicate dMMN amplitude as a biological predictor of future psychosis onset in high-risk individuals, which may be used for early detection and intervention of psychosis.
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http://dx.doi.org/10.1093/cercor/bhaa364DOI Listing
March 2021

Structural MRI Study of the Planum Temporale in Individuals With an At-Risk Mental State Using Labeled Cortical Distance Mapping.

Front Psychiatry 2020 24;11:593952. Epub 2020 Nov 24.

Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.

Recent studies have demonstrated brain structural changes that predate or accompany the onset of frank psychosis, such as schizophrenia, among individuals with an at-risk mental state (ARMS). The planum temporale (PT) is a brain region involved in language processing. In schizophrenia patients, gray matter volume reduction and lack of normal asymmetry (left > right) of PT have repeatedly been reported. Some studies showed progressive gray matter reduction of PT in first-episode schizophrenia patients, and in ARMS subjects during their development of psychosis. MRI scans (1.5 T field strength) were obtained from 73 ARMS subjects and 74 gender- and age-matched healthy controls at three sites (University of Toyama, Toho University and Tohoku University). Participants with ARMS were clinically monitored for at least 2 years to confirm whether they subsequently developed frank psychosis. Cortical thickness, gray matter volume, and surface area of PT were estimated using FreeSurfer-initiated labeled cortical distance mapping (FSLCDM). PT measures were compared among healthy controls, ARMS subjects who later developed overt psychosis (ARMS-P), and those who did not (ARMS-NP). In each statistical model, age, sex, intracranial volume, and scanning sites were treated as nuisance covariates. Of 73 ARMS subjects, 18 developed overt psychosis (12 schizophrenia and 6 other psychoses) within the follow-up period. There were no significant group differences of PT measures. In addition, significant asymmetries of PT volume and surface area (left > right) were found in all diagnostic groups. PT measures did not correlate with the neurocognitive performance of ARMS subjects. Our results suggest that the previously-reported gray matter reduction and lack of normal anatomical asymmetry of PT in schizophrenia patients may not emerge during the prodromal stage of psychosis; taken together with previous longitudinal findings, such PT structural changes may occur just before or during the onset of psychosis.
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http://dx.doi.org/10.3389/fpsyt.2020.593952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732500PMC
November 2020

Rare single-nucleotide DAB1 variants and their contribution to Schizophrenia and autism spectrum disorder susceptibility.

Hum Genome Var 2020 Nov 10;7(1):37. Epub 2020 Nov 10.

Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

Disabled 1 (DAB1) is an intracellular adaptor protein in the Reelin signaling pathway and plays an essential role in correct neuronal migration and layer formation in the developing brain. DAB1 has been repeatedly reported to be associated with neurodevelopmental disorders including schizophrenia (SCZ) and autism spectrum disorders (ASD) in genetic, animal, and postmortem studies. Recently, increasing attention has been given to rare single-nucleotide variants (SNVs) found by deep sequencing of candidate genes. In this study, we performed exon-targeted resequencing of DAB1 in 370 SCZ and 192 ASD patients using next-generation sequencing technology to identify rare SNVs with a minor allele frequency <1%. We detected two rare missense mutations (G382C, V129I) and then performed a genetic association study in a sample comprising 1763 SCZ, 380 ASD, and 2190 healthy control subjects. Although no statistically significant association with the detected mutations was observed for either SCZ or ASD, G382C was found only in the case group, and in silico analyses and in vitro functional assays suggested that G382C alters the function of the DAB1 protein. The rare variants of DAB1 found in the present study should be studied further to elucidate their potential functional relevance to the pathophysiology of SCZ and ASD.
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http://dx.doi.org/10.1038/s41439-020-00125-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655853PMC
November 2020

Rare genetic variants in the gene encoding histone lysine demethylase 4C (KDM4C) and their contributions to susceptibility to schizophrenia and autism spectrum disorder.

Transl Psychiatry 2020 12 5;10(1):421. Epub 2020 Dec 5.

Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Dysregulation of epigenetic processes involving histone methylation induces neurodevelopmental impairments and has been implicated in schizophrenia (SCZ) and autism spectrum disorder (ASD). Variants in the gene encoding lysine demethylase 4C (KDM4C) have been suggested to confer a risk for such disorders. However, rare genetic variants in KDM4C have not been fully evaluated, and the functional impact of the variants has not been studied using patient-derived cells. In this study, we conducted copy number variant (CNV) analysis in a Japanese sample set (2605 SCZ and 1141 ASD cases, and 2310 controls). We found evidence for significant associations between CNVs in KDM4C and SCZ (p = 0.003) and ASD (p = 0.04). We also observed a significant association between deletions in KDM4C and SCZ (corrected p = 0.04). Next, to explore the contribution of single nucleotide variants in KDM4C, we sequenced the coding exons in a second sample set (370 SCZ and 192 ASD cases) and detected 18 rare missense variants, including p.D160N within the JmjC domain of KDM4C. We, then, performed association analysis for p.D160N in a third sample set (1751 SCZ and 377 ASD cases, and 2276 controls), but did not find a statistical association with these disorders. Immunoblotting analysis using lymphoblastoid cell lines from a case with KDM4C deletion revealed reduced KDM4C protein expression and altered histone methylation patterns. In conclusion, this study strengthens the evidence for associations between KDM4C CNVs and these two disorders and for their potential functional effect on histone methylation patterns.
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http://dx.doi.org/10.1038/s41398-020-01107-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719193PMC
December 2020

Evolution of Biomineralization Genes in the Prismatic Layer of the Pen Shell Atrina pectinata.

J Mol Evol 2020 12 24;88(10):742-758. Epub 2020 Nov 24.

Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo, 113-8657, Japan.

Molluscan shells are composed of calcium carbonates, with small amounts of extracellular matrices secreted from mantle epithelial cells. Many types of shell matrix proteins (SMPs) have been identified from molluscan shells or mantle cells. The pen shell Atrina pectinata (Pinnidae) has two different shell microstructures, the nacreous and prismatic layers. Nacreous and prismatic layer-specific matrix proteins have been reported in Pteriidae bivalves, but remain unclear in Pinnidae. We performed transcriptome analysis using the mantle cells of A. pectinata to screen the candidate transcripts involved in its prismatic layer formation. We found Asprich and nine highly conserved prismatic layer-specific SMPs encoding transcript in P. fucata, P. margaritifera, and P. maxima (Tyrosinase, Chitinase, EGF-like proteins, Fibronectin, valine-rich proteins, and prismatic uncharacterized shell protein 2 [PUSP2]) using molecular phylogenetic analysis or multiple alignment. We confirmed these genes were expressed in the epithelial cells of the mantle edge (outer surface of the outer fold) and the mantle pallium. Phylogenetic character mapping of these SMPs was used to infer a possible evolutionary scenario of them in Pteriomorphia. EGF-like proteins, Fibronectin, and valine-rich proteins encoding genes each evolved in the linage leading to four Pteriomorphia (Mytilidae, Pinnidae, Ostreidae, and Pteriidae), PUSP2 evolved in the linage leading to three Pteriomorphia families (Pinnidae, Ostreidae, and Pteriidae), and chitinase was independently evolved as SMPs in Mytilidae and in other Pteriomorphia (Pinnidae, Ostreidae, and Pteriidae). Our results provide a new dataset for A. pectinata SMP annotation, and a basis for understanding the evolution of prismatic layer formation in bivalves.
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http://dx.doi.org/10.1007/s00239-020-09977-7DOI Listing
December 2020

Support vector machine-based classification of schizophrenia patients and healthy controls using structural magnetic resonance imaging from two independent sites.

PLoS One 2020 24;15(11):e0239615. Epub 2020 Nov 24.

Department of Psychiatry, Nagoya University, Graduate School of Medicine, Nagoya, Aichi, Japan.

Structural brain alterations have been repeatedly reported in schizophrenia; however, the pathophysiology of its alterations remains unclear. Multivariate pattern recognition analysis such as support vector machines can classify patients and healthy controls by detecting subtle and spatially distributed patterns of structural alterations. We aimed to use a support vector machine to distinguish patients with schizophrenia from control participants on the basis of structural magnetic resonance imaging data and delineate the patterns of structural alterations that significantly contributed to the classification performance. We used independent datasets from different sites with different magnetic resonance imaging scanners, protocols and clinical characteristics of the patient group to achieve a more accurate estimate of the classification performance of support vector machines. We developed a support vector machine classifier using the dataset from one site (101 participants) and evaluated the performance of the trained support vector machine using a dataset from the other site (97 participants) and vice versa. We assessed the performance of the trained support vector machines in each support vector machine classifier. Both support vector machine classifiers attained a classification accuracy of >70% with two independent datasets indicating a consistently high performance of support vector machines even when used to classify data from different sites, scanners and different acquisition protocols. The regions contributing to the classification accuracy included the bilateral medial frontal cortex, superior temporal cortex, insula, occipital cortex, cerebellum, and thalamus, which have been reported to be related to the pathogenesis of schizophrenia. These results indicated that the support vector machine could detect subtle structural brain alterations and might aid our understanding of the pathophysiology of these changes in schizophrenia, which could be one of the diagnostic findings of schizophrenia.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239615PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685428PMC
January 2021

Complete Genome Sequences of Two Strains of Francisella tularensis subsp. bv. japonica.

Microbiol Resour Announc 2020 Nov 5;9(45). Epub 2020 Nov 5.

Department of Veterinary Science, National Institute of Infectious Diseases, Tokyo, Japan.

, a highly infectious bacterium, is the etiological agent of the zoonotic disease tularemia. It is widely distributed in the Northern Hemisphere, including Japan. Here, we have determined the complete genome sequences of two strains of subsp. bv. japonica isolated from hares in 2008 and 2009.
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http://dx.doi.org/10.1128/MRA.01127-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645672PMC
November 2020

Metal Accumulation Using a Bacterium (K-142) Identified from Environmental Microorganisms by the Screening of Au Nanoparticles Synthesis.

Materials (Basel) 2020 Nov 2;13(21). Epub 2020 Nov 2.

Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.

The use of technology that uses organisms to synthesize metal nanoparticles is necessary to maintain a sustainable society. In this study, we investigated and screened the microorganisms isolated from environmental water by quantifying the reproducibility of synthetic Au nanoparticles and the ability of large amount synthesis. The microorganism (K-142) of the genus showed the best activity in the investigation. K-142 can also synthesize Ag, CdS and PbS nanoparticles, and the deposition efficiency of Ag, Al, Cd, Cu, and Pb was about 64.8-99.2%. According to the observation results under the microscope after fluorescent staining, K-142 could survive after being treated with 0.5 mM metal solution for 24 h. Therefore, it is expected that K-142, which is easy to cultivate, would also have a high ability to reduce and deposit metal substances. K-142 can be applied to the concentration and recovery of heavy metals in environmental water, thereby opening up channels for biological water purification.
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http://dx.doi.org/10.3390/ma13214922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662954PMC
November 2020

Purification, crystallization and X-ray analysis of Pf-SCP (sarcoplasmic Ca-binding protein), related to storage and transport of calcium in mantle of Pinctada fucata.

Protein Expr Purif 2021 02 31;178:105781. Epub 2020 Oct 31.

Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan. Electronic address:

Pf-SCP, a 21 kDa protein with two EF-hand motifs and a phosphorylation site, was identified from mantle tissue and binds to calcium ions and transports calcium components from cell to the shell of Pinctada fucata. To reveal the molecular basis of the calcium binding activity of Pf-SCP, we expressed the recombinant protein of full-length Pf-SCP in Escherichia coli. Recombinant Pf-SCP (rPf-SCP) purified by Ni affinity chromatography and size exclusion chromatography appeared as a single band on SDS-PAGE. The circular dichroism spectroscopy showed that the α-helix content decreased when rPf-SCP interacted with both calcium ions and calcium carbonate. Western blotting and immunostaining verified the Pf-SCP expression in the shell and localization most in the mantle epithelial cells. To further understand the structural and functional regulation of Pf-SCP by calcium ions and calcium carbonate, the crystallization experiments of rPf-SCP in the presence of calcium ions were performed. A crystal of rPf-SCP obtained in the presence of calcium ions diffracted X-rays up to a resolution of 1.8 Å. The space group of the crystal is C2 with unit cell parameters of a = 96.828 Å, b = 55.906 Å, c = 102.14 Å and β = 90.009°, indicating that three molecules of rPf-SCP are contained in an asymmetric unit as estimated at the value of the Matthews coefficient. These results suggest that Pf-SCP may play a role in calcium ions transportation and shell mineralization by concentrating calcium ions inside the mantle epithelial cells and interacting with calcium carbonate molecules.
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http://dx.doi.org/10.1016/j.pep.2020.105781DOI Listing
February 2021

Identification of methionine -rich insoluble proteins in the shell of the pearl oyster, Pinctada fucata.

Sci Rep 2020 10 27;10(1):18335. Epub 2020 Oct 27.

Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.

The molluscan shell is a biomineral that comprises calcium carbonate and organic matrices controlling the crystal growth of calcium carbonate. The main components of organic matrices are insoluble chitin and proteins. Various kinds of proteins have been identified by solubilizing them with reagents, such as acid or detergent. However, insoluble proteins remained due to the formation of a solid complex with chitin. Herein, we identified these proteins from the nacreous layer, prismatic layer, and hinge ligament of Pinctada fucata using mercaptoethanol and trypsin. Most identified proteins contained a methionine-rich region in common. We focused on one of these proteins, NU-5, to examine the function in shell formation. Gene expression analysis of NU-5 showed that NU-5 was highly expressed in the mantle, and a knockdown of NU-5 prevented the formation of aragonite tablets in the nacre, which suggested that NU-5 was required for nacre formation. Dynamic light scattering and circular dichroism revealed that recombinant NU-5 had aggregation activity and changed its secondary structure in the presence of calcium ions. These findings suggest that insoluble proteins containing methionine-rich regions may be important for scaffold formation, which is an initial stage of biomineral formation.
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http://dx.doi.org/10.1038/s41598-020-75444-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591529PMC
October 2020

Involvement of subdomain II in the recognition of acetyl-CoA revealed by the crystal structure of homocitrate synthase from Sulfolobus acidocaldarius.

FEBS J 2021 03 8;288(6):1975-1988. Epub 2020 Sep 8.

Biotechnology Research Center, The University of Tokyo, Japan.

Homocitrate synthase (HCS) catalyzes the aldol condensation of α-ketoglutarate and acetyl coenzyme A to form homocitrate, which is the first committed step of lysine biosynthesis through the α-aminoadipate pathway in yeast, fungi, and some prokaryotes. We determined the crystal structure of a truncated form of HCS from a hyperthermophilic acidophilic archaeon, Sulfolobus acidocaldarius, which lacks the RAM (Regulation of amino acid metabolism) domain at the C terminus serving as the regulatory domain for the feedback inhibition by lysine, in complex with α-ketoglutarate, Mg , and CoA. This structure coupled with mutational analysis revealed that a subdomain, subdomain II, connecting the N-terminal catalytic domain and C-terminal RAM domain is involved in the recognition of acetyl-CoA. This is the first structural evidence of the function of subdomain II in the related enzyme family, which will lead to a better understanding of the catalytic mechanism of HCS. DATABASES: Structural data are available in the RCSB PDB database under the accession number 6KTQ.
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http://dx.doi.org/10.1111/febs.15527DOI Listing
March 2021

Dioctatin Activates ClpP to Degrade Mitochondrial Components and Inhibits Aflatoxin Production.

Cell Chem Biol 2020 11 3;27(11):1396-1409.e10. Epub 2020 Sep 3.

Department of Biosciences, Faculty of Science and Engineering, Teikyo University, 1-1 Toyosatodai, Utsunomiya-shi, Tochigi 320-0003, Japan. Electronic address:

Aflatoxin contamination of crops is a serious problem worldwide. Utilization of aflatoxin production inhibitors is attractive, as the elucidation of their modes of action contributes to clarifying the mechanism of aflatoxin production. Here, we identified mitochondrial protease ClpP as the target of dioctatin, an inhibitor of aflatoxin production of Aspergillus flavus. Dioctatin conferred uncontrolled caseinolytic capacity on ClpP of A. flavus and Escherichia coli. Dioctatin-bound ClpP selectively degraded mitochondrial energy-related proteins in vitro, including a subunit of respiratory chain complex V, which was also reduced by dioctatin in a ClpP-dependent manner in vivo. Dioctatin enhanced glycolysis and alcohol fermentation while reducing tricarboxylic acid cycle metabolites. These disturbances were accompanied by reduced histone acetylation and reduced expression of aflatoxin biosynthetic genes. Our results suggest that dioctatin inhibits aflatoxin production by inducing ClpP-mediated degradation of mitochondrial energy-related components, and that mitochondrial energy metabolism functions as a key determinant of aflatoxin production.
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http://dx.doi.org/10.1016/j.chembiol.2020.08.006DOI Listing
November 2020

Association between self-reported hearing loss and low socioeconomic status in Japan: findings from the Toyama dementia survey.

BMC Geriatr 2020 08 5;20(1):275. Epub 2020 Aug 5.

Department of Neuropsychiatry, School of Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.

Background: Age-related hearing loss reduces the quality of life in older adults. Low socioeconomic status (SES) has been reported as a risk factor for hearing loss, although this has not been verified in Japan. This study aimed to assess the association between low SES and hearing loss, excluding people with dementia, in Japan.

Methods: Data from the Toyama Dementia Survey, Japan, were used. Overall, 126 patients with hearing loss and 913 unimpaired controls were identified. Participants' presentation of dementia, self-reported hearing loss, history of medically diagnosed disease (hypertension, hyperlipidemia, diabetes, stroke, or angina pectoris/cardiovascular disease), lifestyle factors (alcohol consumption and smoking), and SES (educational attainment and occupation) were assessed. Any association between low SES and hearing loss was investigated using logistic regression analysis.

Results: The odds ratio (OR) for hearing loss was higher for participants with low educational attainment than for those with high educational attainment (age- and sex-adjusted OR 3.08; 95% confidence intervals [CI], 1.51-6.28). After adjusting the models for SES, lifestyle factors, and medical history, the OR increased from 2.90 (95% CI, 1.40-6.01) to 3.43 (95% CI, 1.62-7.27). The OR for hearing loss for participants with blue-collar jobs compared with that of participants with white-collar jobs was not significant (age- and sex-adjusted OR, 1.45; 95% CI, 0.93-2.25). Older age and a history of angina pectoris or cardiovascular disease were found to increase the risk of hearing loss.

Conclusions: Low educational attainment was independently associated with hearing loss in older adults without dementia in Japan.
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http://dx.doi.org/10.1186/s12877-020-01680-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405336PMC
August 2020

Gray Matter Changes in the Insular Cortex During the Course of the Schizophrenia Spectrum.

Front Psychiatry 2020 10;11:659. Epub 2020 Jul 10.

Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.

Progressive gray matter reductions in the insular cortex have been reported in the early phases of schizophrenia (Sz); however, the trajectory of these reductions during the course of the illness currently remains unclear. Furthermore, it has not yet been established whether patients with schizotypal (SzTypal) features exhibit progressive changes in the insular cortex. This follow-up magnetic resonance imaging study examined volume changes in the short and long insular cortices (mean inter-scan interval = 2.6 years) of 23 first-episode (FE) and 17 chronic patients with Sz, 14 with SzTypal disorder, and 21 healthy controls. Baseline comparisons revealed smaller insular cortex volumes bilaterally in Sz patients (particularly in the chronic group) than in SzTypal patients and healthy controls. FESz patients showed significantly larger gray matter reductions in the insular cortex over time (left: -3.4%/year; right: -2.9%/year) than those in healthy controls (-0.1%/year for both hemispheres) without the effect of subregion or antipsychotic medication, whereas chronic Sz (left: -1.5%/year; right: -1.6%/year) and SzTypal (left: 0.5%/year; right: -0.6%/year) patients did not. Active atrophy of the right insular cortex during FE correlated with fewer improvements in positive symptoms in the Sz groups, while mild atrophy of the left insular cortex during the chronic phase was associated with the severity of negative symptoms in the follow-up period. The present results support dynamic volumetric changes in the insular cortex being specific to overt Sz among the spectrum disorders examined and their degree and role in symptomatology appear to differ across the illness stages.
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http://dx.doi.org/10.3389/fpsyt.2020.00659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366364PMC
July 2020

Characterization of the chalky layer-derived EGF-like domain-containing protein (CgELC) in the pacific oyster, Crassostrea gigas.

J Struct Biol 2020 10 29;212(1):107594. Epub 2020 Jul 29.

Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo, Tokyo 113-8657, Japan. Electronic address:

The shells of the Pacific oyster Crassostrea gigas contain calcite crystals with three types of microstructures: prismatic, chalky, and foliated layers. Many shell matrix proteins were annotated from the shells of C. gigas; however, it is unclear which SMPs play important roles in their shell mineralization. The matrix proteins have never been reported from the chalky layer. In this study, we identified a chalky layer-derived EGF-like domain-containing protein (CgELC) from the chalky layer of C. gigas shells. The gene sequence of the CgELC was encoded under CGI_ 10,017,544 of the C. gigas genome database. Only peptide fragments in the N-terminal region of CGI_ 10,017,544 were detected by LC-MS/MS analyses, suggesting that CGI_ 10,017,544 was digested at the predicted protease digestion dibasic site by post-translational modification to become a mature CgELC protein. We produced three types of CgELC recombinant proteins, namely, the full length CgELC, as well as the N-terminal and C-terminal parts of CgELC (CgELC-N or -C, respectively), for in vitro crystallization experiments. In the presence of these recombinant proteins, the aggregation of polycrystalline calcite was observed. Some fibrous organic components seemed to be incorporated into the calcite crystals in the presence of the r-CgELC protein. We also noted different features in the crystallization between CgELC-N and CgELC-C; some crystals were inhibited crystal plane formation and contained many columnar prisms inside the crystals (CgELC-N) and formed numerous holes on their surfaces (CgELC-C). These results suggest that CgELC is involved in crystal aggregation and incorporated into calcite crystals.
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http://dx.doi.org/10.1016/j.jsb.2020.107594DOI Listing
October 2020
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