58 research outputs found

    RacGAP α2-Chimaerin Function in Development Adjusts Cognitive Ability in Adulthood

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    SummaryA major concern in neuroscience is how cognitive ability in adulthood is affected and regulated by developmental mechanisms. The molecular bases of cognitive development are not well understood. We provide evidence for the involvement of the α2 isoform of Rac-specific guanosine triphosphatase (GTPase)-activating protein (RacGAP) α-chimaerin (chimerin) in this process. We generated and analyzed mice with global and conditional knockouts of α-chimaerin and its isoforms (α1-chimaerin and α2-chimaerin) and found that α-chimaerin plays a wide variety of roles in brain function and that the roles of α1-chimaerin and α2-chimaerin are distinct. Deletion of α2-chimaerin, but not α1-chimaerin, beginning during early development results in an increase in contextual fear learning in adult mice, whereas learning is not altered when α2-chimaerin is deleted only in adulthood. Our findings suggest that α2-chimaerin acts during development to establish normal cognitive ability in adulthood

    Cation-Disordered Li3VO4: Reversible Li Insertion/Deinsertion Mechanism for Quasi Li-Rich Layered Li1+x[V1/2Li1/2]O2 (x = 0–1)

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    The reversible lithiation/delithiation mechanism of the cation-disordered Li3VO4 material was elucidated, including the understanding of structural and electrochemical signature changes during cycling. The initial exchange of two Li induces a progressive and irreversible migration of Li and V ions from tetrahedral to octahedral sites, confirmed by the combination of in situ/operando X-ray diffraction and X-ray absorption fine structure analyses. The resulting cation-disordered Li3VO4 can smoothly and reversibly accommodate two Li and shows a Li+ diffusion coefficient larger by 2 orders of magnitude than the one of pristine Li3VO4, leading to improved electrochemical performance. This cation-disordered Li3VO4 negative electrode offers new opportunities for designing high-energy and high-power supercapacitors. Furthermore, it opens new paths for preparing disordered compounds with the general hexagonal close-packing structure, including most polyanionic compounds, whose electrochemical performance can be easily improved by simple cation mixing

    Ultrafast charge–discharge characteristics of a nanosized core–shell structured LiFePO4 material for hybrid supercapacitor applications

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    Highly dispersed crystalline/amorphous LiFePO4 (LFP) nanoparticles encapsulated within hollow-structured graphitic carbon were synthesized using an in situ ultracentrifugation process. Ultracentrifugation triggered an in situ sol–gel reaction that led to the formation of core–shell LFP simultaneously hybridized with fractured graphitic carbon. The structure has double cores that contain a crystalline LFP (core 1) covered by an amorphous LFP containing Fe3+ defects (core 2), which are encapsulated by graphitic carbon (shell). These core–shell LFP nanocomposites show improved Li+ diffusivity thanks to the presence of an amorphous LFP phase. This material enables ultrafast discharge rates (60 mA h g-1 at 100C and 36 mA h g-1 at 300C) as well as ultrafast charge rates (60 mA h g-1 at 100C and 36 mA h g-1 at 300C). The synthesized core–shell nanocomposites overcome the inherent one-dimensional diffusion limitation in LFP and yet deliver/store high electrochemical capacity in both ways symmetrically up to 480C. Such a high rate symmetric capacity for both charge and discharge has never been reported so far for LFP cathode materials. This offers new opportunities for designing high-energy and high-power hybrid supercapacitors

    Japanese nationwide questionnaire survey on delayed cerebral infarction due to vasospasm after subarachnoid hemorrhage

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    Background and purposeVarious prophylactic drugs for cerebral vasospasm and delayed cerebral infarction (DCI) after subarachnoid hemorrhage (SAH) have been used in Japan. To investigate the treatment trends for cerebral vasospasm and frequency of DCI after SAH throughout Japan in 2021.MethodsIn 2021 we conducted an anonymous questionnaire survey on management for preventing cerebral vasospasm after aneurysmal SAH, and the frequency of DCI. The questionnaire was emailed to 955 certified neurosurgeons at 553 hospitals in Japan. Of them, 162 hospitals (29% response rate) responded to the questionnaire. Of these, 158 were included in this study, while four hospitals that responded insufficiently were excluded. The efficacy of treatments for reducing DCI were examined through a logistic regression analysis.ResultsAmong 3,093 patients treated with aneurysmal SAH, 281 patients (9.1%) were diagnosed with DCI related to cerebral vasospasm. Coil embolization had significantly lower DCI frequency (6.9%), compared to microsurgical clipping (11.8%, odds ratio, 0.90; 95% confidential intervals, 0.84–0.96; P, 0.007). In addition, cilostazol administration was associated with significantly lower DCI frequency (0.48; 0.27–0.82; 0.026). The efficacy of cilostazol in reducing DCI remained unchanged after adjustment for covariates. The most effective combination of multiple prophylactic drugs in reducing DCI related to cerebral vasospasm was cilostazol, fasudil, and statin (0.38; 0.22–0.67; 0.005).ConclusionsThis study elucidated the trends in prophylactic drugs to prevent cerebral vasospasm and frequency of DCI after aneurysmal SAH in Japan. Coil embolization and cilostazol administration showed effectiveness in reducing DCI related to cerebral vasospasm in 2021

    Stabilizing the Structure of LiCoPO4 Nanocrystals via Addition of Fe3+: Formation of Fe3+ Surface Layer, Creation of Diffusion-Enhancing Vacancies, and Enabling High-Voltage Battery Operation

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    Factors affecting the cyclability of the Fe-substituted LiCoPO4 (LiCo0.8Fe0.2PO4, LCFP) material were elucidated, including both the structural and electrode/electrolyte stability. Electrochemical characterization of the synthesized LCFP nanoparticles lends clear evidence for improved electrochemical stability of LCP, as well as enhanced rate capability, with Fe3+ substitution. Surface analysis using X-ray photoelectron spectroscopy (XPS) and electron energy loss spectroscopy (EELS) suggest that Fe enrichment on the surface of LCFP occurs through the oxidation of Fe2+ into Fe3+ in the synthesis process. The Fe3+-rich phase on the LCP surface enhances the stability of the delithiated phase, preventing oxidative reactions with electrolytes during high-voltage operation. This surface protection persists as long as the electrochemical reduction of Fe3+ is avoided by ensuring that the full range of operating voltages lie above the Fe3+/Fe2+ redox potential. Our findings may offer new approaches to stabilize the structure of LCP and other high-voltage positive electrodes for use in 5 V-class Li-ion batteries

    Amino acid polymorphisms in human histocompatibility leukocyte antigen class II and proinsulin epitope have impacts on type 1 diabetes mellitus induced by immune-checkpoint inhibitors

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    IntroductionImmune-checkpoint inhibitors are effective in various advanced cancers. Type 1 diabetes mellitus induced by them (ICI-T1DM) is a serious complication requiring prompt insulin treatment, but the immunological mechanism behind it is unclear.MethodsWe examined amino acid polymorphisms in human histocompatibility leukocyte antigen (HLA) molecules and investigated proinsulin epitope binding affinities to HLA molecules.Results and DiscussionTwelve patients with ICI-T1DM and 35 patients in a control group without ICI-T1DM were enrolled in the study. Allele and haplotype frequencies of HLA-DRB1*04:05, DQB1*04:01, and most importantly DPB1*05:01 were significantly increased in patients with ICI-T1DM. In addition, novel amino acid polymorphisms in HLA-DR (4 polymorphisms), in DQ (12 polymorphisms), and in DP molecules (9 polymorphisms) were identified. These amino acid polymorphisms might be associated with the development of ICI-T1DM. Moreover, novel human proinsulin epitope clusters in insulin A and B chains were discovered in silico and in vitro peptide binding assays to HLA-DP5. In conclusion, significant amino acid polymorphisms in HLA-class II molecules, and conformational alterations in the peptide-binding groove of the HLA-DP molecules were considered likely to influence the immunogenicity of proinsulin epitopes in ICI-T1DM. These amino acid polymorphisms and HLA-DP5 may be predictive genetic factors for ICI-T1DM

    Noncrystalline Nanocomposites as a Remedy for the Low Diffusivity of Multivalent Ions in Battery Cathodes

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    Rechargeable batteries using multivalent metals are among the most promising next-generation battery systems due to their high capacity, high safety, and low cost compared with lithium-ion batteries. However, strong cation−anion interaction degrades diffusion in solid cathodes, an effect that must be mitigated to yield practical multivalent metal batteries. We show that a highly defective iron phosphate−carbon composite prepared by ultracentrifugation serves as a reversible insertion/deinsertion for magnesium ions with, and operates beyond, a 2-V cell voltage at room temperature. A composite of noncrystalline particles that embeds the surrounding carbon structure enhances the magnesium-ion diffusion in the solid phase with stability for cycle life. X-ray absorption spectroscopy, transmission electron microscopy with energy-dispersive X-ray spectroscopy, and high-energy X-ray scattering measurements demonstrate magnesium-ion insertion and extraction in the defective iron phosphate without conversion reactions. This work suggests promising applications for highly defective structures as intercalation hosts for multivalent ions

    青森県内の精神科デイケア利用者に対する 動脈硬化の予防的指導に向けた実態調査:上腕- 足首脈波伝播速度(baPWV)と生活習慣関連要因についての研究

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    Objective: For psychiatric day care users, improvement and maintenance of specific neurologicalmanifestations and support for living activities have been focused on. However, few surveys on unhealthylifestyle in the current state have been performed even though a higher prevalence of metabolic syndrome(MetS) than in inpatients and cardiometabolic risk have been reported. In this study, the relationshipbetween brachial-ankle pulse wave velocity (baPWV) and lifestyle-related factors was investigated inpsychiatric day care users in Aomori Prefecture, Japan.Methods: The subjects were 109 psychiatric day care users at medical institutions in Aomori Prefecture(male: 62, female: 47). The measurement items were age, sex, height, body weight, BMI, body fatpercentage, grip strength, blood pressure, pulse pressure, mean blood pressure, and baPWV. Using a selfcompletedquestionnaire, we obtained the following information from each subject: smoking amount(pack-years), history of present illness, past medical history, confirmation of drug history handbook, andthe presence of exercise habits.Results: In males in the 20–39 years old group, no significant correlation was noted between the baPWVvalue and lifestyle-related factors. On the other hand, in female in the corresponding group, a significantpositive correlation was noted between the baPWV value and BMI and body fat percentage (p<0.001,p<0.001). In the 40–49 and 50 years old or older groups, no significant correlation was noted betweenthe baPWV value and lifestyle-related factors in males or females.Conclusion: For psychiatric day care users, in addition to conventional improvement of neurologicalmanifestations and support for living activities, comprehensive approaches to poor physical health areimportant. Taking measures against by sex and age may delay the progression of atherosclerosis,which is the outcome of poor physical health
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