Characteristic microglial features in patients with hereditary diffuse leukoencephalopathy with spheroids.

OBJECTIVE: To clarify the histopathological alterations of microglia in the brains of patients with hereditary diffuse leukoencephalopathy with spheroids (HDLS) caused by mutations of the gene encoding the colony stimulating factor-1 receptor (CSF-1R). METHODS: We examined 5 autopsied brains and 1 biopsy specimen from a total of 6 patients with CSF-1R mutations. Detailed immunohistochemical, biochemical, and ultrastructural features of microglia were examined, and quantitative analyses were performed. RESULTS: In layers 3 to 4 of the frontal cortex in HDLS brains, microglia showed relatively uniform and delicate morphology, with thin and winding processes accompanying knotlike structures, and significantly smaller areas of Iba1 immunoreactivity and lower numbers of Iba1-positive cells were evident in comparison with control brains. On the other hand, in layers 5 to 6 and the underlying white matter, microglia were distributed unevenly; that is, in some areas they had accumulated densely, whereas in others they were scattered. Immunoblot analyses of microglia-associated proteins, including CD11b and DAP12, revealed that HDLS brains had significantly lower amounts of these proteins than diseased controls, although Ki-67-positive proliferative microglia were not reduced. Ultrastructurally, the microglial cytoplasm and processes in HDLS showed vesiculation of the rough endoplasmic reticulum and disaggregated polyribosomes, indicating depression of protein synthesis. On the other hand, macrophages were immunonegative for GLUT-5 or P2ry12, indicating that they were derived from bone marrow. INTERPRETATION: The pathogenesis of HDLS seems to be associated with microglial vulnerability and morphological alterations. Ann Neurol 2016;80:554-565.

Interface structure between tetraglyme and graphite.

Clarification of the details of the interface structure between liquids and solids is crucial for understanding the fundamental processes of physical functions. Herein, we investigate the structure of the interface between tetraglyme and graphite and propose a model for the interface structure based on the observation of frequency-modulation atomic force microscopy in liquids. The ordering and distorted adsorption of tetraglyme on graphite were observed. It is found that tetraglyme stably adsorbs on graphite. Density functional theory calculations supported the adsorption structure. In the liquid phase, there is a layered structure of the molecular distribution with an average distance of 0.60 nm between layers.

Neuronal differentiation associated with Gli3 expression predicts favorable outcome for patients with medulloblastoma.

Medulloblastoma (MB) is a malignant cerebellar tumor arising in children, and its ontogenesis is regulated by Sonic Hedgehog (Shh) signaling. No data are available regarding the correlation between expression of Gli3, a protein lying downstream of Shh, and neuronal differentiation of MB cells, or the prognostic significance of these features. We re-evaluated the histopathological features of surgical specimens of MB taken from 32 patients, and defined 15 of them as MB with neuronal differentiation (ND), three as MB with both glial and neuronal differentiation (GD), and 14 as differentiation-free (DF) MB. Gli3-immunoreactivity (IR) was evident as a clear circular stain outlining the nuclei of the tumor cells. The difference in the frequency of IR between the ND+GD (94.4%) and DF (0%) groups was significant (P < 0.001). The tumor cells with ND showed IR for both Gli3 and neuronal nuclei. Ultrastructurally, Gli3-IR was observed at the nuclear membrane. The overall survival and event-free survival rates of the patients in the ND group were significantly higher than those in the other groups. The expression profile of Gli3 is of considerable significance, and the association of ND with this feature may be prognostically favorable in patients with MB.

Composition-dependent electrocatalytic activity of AuPd alloy nanoparticles prepared via simultaneous sputter deposition into an ionic liquid.

Homogeneously alloyed bimetallic particles of AuPd with an average size of ca. 2 nm were successfully prepared by simultaneous sputter deposition of Au and Pd in an ionic liquid in the absence of any additional stabilizing agents. The chemical composition of the AuPd alloy was tunable depending on the area fraction of Au plates in the Au-Pd binary targets for sputtering. The particles were immobilized on an HOPG surface by heat treatment along with the increase in the average size of particles from ca. 2 nm to ca. 7 nm. Ionic liquid species adsorbed on the as-prepared AuPd nanoparticle films on HOPG caused the prevention of electrocatalytic reactions, but repetition of potential sweep cycling in a basic aqueous solution removed the adsorbed ionic species, resulting in electrocatalytic oxidation of ethanol at the AuPd alloy nanoparticle-immobilized HOPG electrode. The electrocatalytic activity of AuPd nanoalloy particles varied upon changing the fraction of Au and Pd in the particles, and alloy particles having an Au fraction of ca. 0.61 exhibited the maximum activity against ethanol oxidation, being higher than the activity of the pure Pt surface.

Kinetic analysis of silicon-lithium alloying reaction in silicon single crystal using soft X-ray absorption spectroscopy.

Silicon has been considered to be one of the most promising anode active materials for next-generation lithium-ion batteries due to its large theoretical capacity (4200 mA h g-1, Li22Si5). However, silicon anodes suffer from degradation due to large volume expansion and contraction. To control the ideal particle morphology, an experimental method is required to analyze anisotropic diffusion and surface reaction phenomena. This study investigates the anisotropy of the silicon-lithium alloying reaction using electrochemical measurements and Si K-edge X-ray absorption spectroscopy on silicon single crystals. During the electrochemical reduction process in lithium-ion battery systems, the continuous formation of solid electrolyte interphase (SEI) films prevents the achievement of steady-state conditions. Instead, the physical contact between silicon single crystals and lithium metals can prevent the effect of SEI formation. The apparent diffusion coefficient and the surface reaction coefficient are determined from the progress of the alloying reaction analyzed by X-ray absorption spectroscopy. While the apparent diffusion coefficients show no clear anisotropy, the apparent surface reaction coefficient of Si (100) is more significant than that of Si (111). This finding indicates that the surface reaction of silicon governs the anisotropy of practical lithium alloying reaction for silicon anodes.

Recurrence rates and risk factors for seizure recurrence following antiseizure medication withdrawal in adolescent patients with genetic generalized epilepsy.

OBJECTIVE: This study aimed to identify the recurrence rate of genetic generalized epilepsy (GGE) and risk factors for recurrence after antiseizure medication (ASM) withdrawal in adolescent patients. METHODS: We retrospectively reviewed medical records of patients with GGE who were included in the registry at the Department of Child Neurology, National Hospital Organization Nishiniigata Chuo Hospital from 2000 through 2020. The eligibility criteria were as follows: onset of epileptic seizures at <15 years of age, treatment with an ASM, and attempted treatment withdrawal at 10-19 years of age. The rates of seizure recurrence after drug withdrawal were evaluated. Moreover, several variables were evaluated as predictors of recurrence. RESULTS: In total, 77 patients with GGE (21, 13, and 43 patients with juvenile myoclonic epilepsy [JME], juvenile absence epilepsy [JAE], and epilepsy with generalized tonic-clonic seizures alone [EGTCSA], respectively) were included in this study. Recurrence was detected in 68% of patients with GGE (86%, 31%, and 70% of patients with JME, JAE, and EGTCSA, respectively). Recurrence rates for patients who developed epilepsy at ≥13 years of age, those who started dose reduction at ≥16 years of age, those who exhibited a seizure-free period of <36 months before withdrawal, and those who chose to discontinue treatment at their own discretion were significantly higher than those for their counterparts. Multivariate analysis revealed that initiation of dose reduction at ≥16 years of age was associated with increased recurrence risk. Meanwhile, a diagnosis of JAE was associated with decreased recurrence risk. All patients with JAE were treated with valproic acid. SIGNIFICANCE: Antiseizure medication withdrawal at ≥16 years of age and a diagnosis other than JAE may be independent risk factors for seizure recurrence after drug withdrawal in adolescent patients.

123I-BMIPP, a Radiopharmaceutical for Myocardial Fatty Acid Metabolism Scintigraphy, Could Be Utilized in Bacterial Infection Imaging.

In this study, we evaluated the use of 15-(4-123I-iodophenyl)-3(R,S)-methylpentadecanoic acid (123I-BMIPP) to visualize fatty acid metabolism in bacteria for bacterial infection imaging. We found that 123I-BMIPP, which is used for fatty acid metabolism scintigraphy in Japan, accumulated markedly in Escherichia coli EC-14 similar to 18F-FDG, which has previously been studied for bacterial imaging. To elucidate the underlying mechanism, we evaluated changes in 123I-BMIPP accumulation under low-temperature conditions and in the presence of a CD36 inhibitor. The uptake of 123I-BMIPP by EC-14 was mediated via the CD36-like fatty-acid-transporting membrane protein and accumulated by fatty acid metabolism. In model mice infected with EC-14, the biological distribution and whole-body imaging were assessed using 123I-BMIPP and 18F-FDG. The 123I-BMIPP biodistribution study showed that, 8 h after infection, the ratio of 123I-BMIPP accumulated in infected muscle to that in control muscle was 1.31 at 60 min after 123I-BMIPP injection. In whole-body imaging 1.5 h after 123I-BMIPP administration and 9.5 h after infection, infected muscle exhibited a 1.33-times higher contrast than non-infected muscle. Thus, 123I-BMIPP shows potential for visualizing fatty acid metabolism of bacteria for imaging bacterial infections.

A highly sensitive and specific method to evaluate viable fungal burden of Aspergillus fumigatus in mice by RT-qPCR for 18S ribosomal RNA.

Potent fungicidal activity is one of the key factors of antifungals to overcome invasive pulmonary aspergillosis (IPA). To date, quantification of Aspergillus DNA in the lungs and galactomannan (GM) in serum or bronchoalveolar lavage fluid have been developed as general methods for measuring fungal burden in IPA animal models. However, GM quantification is not supposed to be a suitable method for precise evaluation of the fungicidal effects of antifungals, because killed Aspergillus hyphae can release GM for a certain period until they are eliminated by the host. Therefore, in terms of detecting viable fungal burden of Aspergillus, quantification of Aspergillus DNA has been thought to be a suitable method. Here, to obtain a method with much higher sensitivity, we applied reverse transcription quantitative PCR (RT-qPCR) for A. fumigatus 18S ribosomal RNA to measure the viable fungal burden in murine IPA models. Prior to in vivo tests, we confirmed that the sensitivity of 18S rRNA was nearly 50-fold higher than that of 18S ribosomal DNA in vitro. This highly sensitive method made it possible to evaluate the fungicidal effects of antifungals in a low-inoculation murine IPA model. In this model, single administrations of higher doses of voriconazole and posaconazole, which have fungicidal activity, were able to display fungicidal effects with ≥1 log10 reductions by 18S rRNA quantification, whereas significant reductions in serum GM were not observed. These results suggest that 18S rRNA quantification is a powerful tool for screening novel antifungals with potent fungicidal activity only after a single administration.

Size control and immobilization of gold nanoparticles stabilized in an ionic liquid on glass substrates for plasmonic applications.

Gold (Au) nanoparticles were prepared by sputter deposition of Au metal in an ionic liquid (IL) of 1-butyl-3-methylimidazolium hexafluorophosphate (BMI-PF6). The size of Au nanoparticles was increased from 2.6 to 4.8 nm by heat treatment at 373 K. The nanoparticles uniformly dispersed in the IL were densely immobilized on a glass substrate surface modified with a silane coupling agent having an imidazole functional group by spreading the Au particle IL solution on the substrates, followed by heat treatment at 373 K. The optical property of the thus-obtained films was tunable by controlling the size of Au nanoparticles in the IL and the degree of immobilization. An intense localized surface plasmon resonance (LSPR) peak was observed in each Au particle film, and the wavelength of the LSPR peak could be controlled by changing the size of nanoparticles in the IL solution before immobilization. Photoexcitation of the LSPR peak caused enhancement of the photoluminescence of CdTe nanoparticles immobilized on Au nanoparticle films, probably due to the locally enhanced electric field formed around Au nanoparticles.

Widespread ischemic brain lesions caused by vasculopathy associated with neurofibromatosis type 1.

We report the autopsy findings of a 63-year-old man with neurofibromatosis type 1 (NF1), in whom widespread ischemic brain lesions caused by vasculopathy associated with the disorder were observed. The patient, who had café au lait macules, axillary freckling, and neurofibromas, was inarticulate of speech, had difficulty in maintaining a sitting position, and was hyporeactive at the age of 57 years. He then developed autonomic dysfunction, followed by consciousness disturbance and status epilepticus. Repeated MRI studies disclosed multiple, ill-defined lesions in the brain and progressive cerebral atrophy. The histopathological features of the lesions were those of ischemia that had occurred with spatiotemporal variability in the brain. Characteristically, many arteries in the subarachnoid space manifested accumulation of cells in the intimal layer: this hyperplasia had resulted in narrowing and occlusion of the lumen. Immunoblotting demonstrated a marked decrease of neurofibromin, the NF1 product, which is known to act as a functional molecule in the normal process of vascular maintenance and repair. This case provides useful information about the pathomechanisms underlying central nervous system manifestations in patients with NF1.

Alzheimer's disease: report of two autopsy cases with a clinical diagnosis of corticobasal degeneration.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Corticobasal degeneration (CBD) is a rare neurodegenerative disease affecting adults, being characterized clinically by a combination of extrapyramidal signs and focal cortical syndromes. In both diseases, tau deposits are a characteristic neuropathological feature. We report two new patients with autopsy-proven AD, in whom clinical diagnoses of CBD were made during life. The ages of the patients at onset were 52 and 67 years, and the disease durations were 9 and 15 years, respectively. At autopsy, both cases exhibited marked cortical atrophy with evident neuronal loss in the convex areas of the frontal and parietal lobes. Immunohistochemically, AT8-positive neurofibrillary tangles (NFTs) and Abeta-positive senile plaques (SPs) were widespread and abundant in the cerebral cortex (Alzheimer pathology stage VI/C of Braak and Braak), leading us to the final pathological diagnosis of AD. No tau lesions suggestive of CBD were observed, and the deep gray matter areas, including the substantia nigra, were unremarkable (exceptionally, only mild neuronal loss was noted in the putamen in case 2). These findings further strengthen the idea that in AD, neurodegeneration with tau and Abeta deposits may begin in the fronto-parietal neocortical areas, which are often preferentially affected in CBD, earlier than, or as early as the medial temporal lobe, and that extrapyramidal signs, such as rigidity and tremor, can occur in the absence of neuronal loss in the basal ganglia and substantia nigra.

Two-Phase Reaction Mechanism for Fluorination and Defluorination in Fluoride-Shuttle Batteries: A First-Principles Study.

Fluoride-shuttle batteries (FSBs), which are based on fluoride-ion transfer, have attracted attention because of their high theoretical energy densities. The fluorination and defluorination reactions at the electrodes are the possible rate-determining steps in FSBs, and understanding the mechanism is important to achieve smooth charge/discharge. In this study, we discuss the thermodynamically favored pathways for the fluorination and defluorination reactions and compare the reactions through the solid-solution and two-phase-coexistent states by density functional theory (DFT) calculations. The free energies of the solid-solution and two-phase states approximate the energies calculated by DFT, and their accuracy was validated by comparison with experimental formation enthalpies and free energies. The relative formation enthalpies of typical, transition, and relativistic metal (Tl, Pb, and Bi) fluorides are well reproduced by DFT calculations within 0.1, 0.2, and 0.4 eV, respectively. We also show that the reaction pathway can be determined by comparing the formation enthalpies of the metal fluoride H, a fluorine vacancy HV, and an interstitial fluorine defect HI from the simple selection rule. The enthalpy relation of HI > H > -HV observed in all the calculations strongly suggests that fluorination and defluorination in FSB electrodes occur by a two-phase reaction. This fluorination and defluorination mechanism will be useful to clarify the rate-determining step in FSBs.

Electrochemical deposition of gold frame structure on silver nanocubes.

Au-framed Ag nanocubes were prepared by site-selective electrochemical deposition of Au onto the edges and vertices of Ag nanocubes modified with a self-assembled monolayer (SAM) of 1-octanethiol, and further chemical etching of the Ag cubes used as a template produced Au nanoframes.

Photochemical shape control of cadmium sulfide nanorods coated with an amorphous silica thin layer.

The surface of cadmium sulfide nanorods was modified by 3-mercaptopropyltrimethoxysilane, followed by the hydrolysis of trimethoxysilyl groups to form a silica shell structure (SiO2/CdS[rod]). Size-selective photoetching was applied to SiO2/CdS[rod] to modify the size of the CdS rod core. The absorption spectra were blue-shifted by irradiation of monochromatic light, and finally absorption onset agreed with the wavelength of irradiation light. These facts indicated that CdS rod particles were photoetched to smaller ones until the irradiated photons were no longer absorbed by the photoetched particles and that the SiO2 shell layer surrounding the CdS rod core prevented coalescence between photoetched particles. Changes in the wavelength of irradiation light from 488 to 436 nm caused a decrease in rod width from 3.5 to 2.3 nm along with remarkable decrease in the length of rod from 14 to 4.2 nm, suggesting that the photoetching rate was dependent on the kind of crystal faces and that the photocorrosion reactions at the tips of the CdS rod, that is, on (001) and/or (001) faces, were faster than those on other faces that appeared on the sides of the rod. This technique enabled control of CdS rod shape by selecting the wavelength of irradiation light.

Photo-induced electron migrations in the nano-cavities of mesoporous silica sensitized by a cationic porphyrin dye.

Photo-induced redox reactions in a hybrid film of a cationic porphyrin dye (H2TMPyP) accommodated within a transparent mesoporous silica (MPS) film spin-coated on an FTO electrode have been investigated for such applications as the construction of efficient solar energy storage devices and novel light-stimulated sensors. In this system, anodic and cathodic photocurrents were observed under bias voltages of +0.3 V and -0.4 V, respectively. The action spectrum of the photocurrents corresponded well with the absorbance of the H2TMPyP molecules in the visible light region. Control experiments showed no photocurrents for the mesoporous silica without H2TMPyP. Our investigations showed that the H2TMPyP molecules function not only as a sensitizer but also as a mediator for electron migrations within mesoporous nano-cavities.

Candida albicans, Cryptococcus neoformans or Aspergillus fumigatus induces an antifungal activity in mouse serum, which is different from transferrin.

It has been reported that administration of Candida albicans into mouse induces an antifungal activity in serum, which has been identified as transferrin. In the present study, we show that not only C. albicans, but also other fungus such as Cryptococcus neoformans or Aspergillus fumigatus similarly can induce an antifungal activity in mouse serum. This antifungal activity was inhibited by the addition of ferrous ion, indicating that the growth inhibition of C. albicans was due to deficiency of ferrous ion, which may be caused by transferrin. Indeed, addition of transferrin in an in vitro assay system using RPMI1640 culture medium inhibited the growth of C. albicans, C. neoformans or A. fumigatus. However, when C. albicans was grown in RPMI1640 medium with 10% fetal bovine serum (FBS), transferrin was unable to inhibit the growth of C. albicans, in sharp contrast, when C. albicans treated mouse serum was added instead of FBS, the growth of the organism was inhibited. Similar results were obtained when C. neoformans or A. fumigatus was used. Taken together, the results suggest that antifungal activity induced by C. albicans, C. neoformans or A. fumigatus was not due to transferrin but likely due to other unknown serum proteins, which may cut off the source of iron for the growth of these fungi.

Evolution of Reactions of a Fluoride Shuttle Battery at the Surfaces of BiF3 Microclusters Studied by In†Situ Raman Microscopy.

Fluoride shuttle batteries (FSBs), which utilize defluorination of metal fluorides and fluorination of the resultant metals, are expected to have high energy densities. In situ Raman microscopy was conducted during FSB reactions of a nearly-2D cluster of orthorhombic BiF3 microparticles partly embedded in a gold-plated film (o-BiF3 /gold). At a high overpotential, defluorination of the surface of an o-BiF3 particle (or cluster) was almost completed within approximately 120 s. At a low over potential, defluorination proceeded from the contours of the cluster that was in contact with the gold to the center of the cluster, suggesting that the rate-limiting process was electronic diffusion. Conversely, fluorination proceeded uniformly at the surface of the cluster to form BiF3 with a cubic structure (c-BiF3 ). The results will lead to the establishment of a strategy for efficient use of active materials with low electronic and ionic conductivities.

Single-step synthesis of gold-silver alloy nanoparticles in ionic liquids by a sputter deposition technique.

The simultaneous sputter deposition of gold and silver onto ionic liquids formed bimetallic alloy nanoparticles, which exhibited composition-sensitive surface plasmon resonance, the peak wavelength being red-shifted with an increase in the surface area of the gold foil targets sputtered.

Photocatalytic syntheses of azoxybenzene by visible light irradiation of silica-coated cadmium sulfide nanocomposites.

Photoirradiation (lambda= 436 nm) of a deaerated 2-propanol aqueous solution containing nitrobenzene and rhodium-loaded silica-coated cadmium sulfide nanoparticles produced azoxybenzene with relatively high selectivity (68%), the photocatalytic activity being enhanced with a decrease in the size of the semiconductor particle core.

Photochemical fine-tuning of luminescent color of cadmium selenide nanoparticles: fabricating a single-source multicolor luminophore.

Size-selective photoetching was applied to silica-coated cadmium selenide (SiO2/CdSe) nanoparticles to precisely control their photoluminescence properties. The absorption spectra of CdSe was blue-shifted by irradiation of monochromatic light, and finally, the absorption onset agreed with the wavelength of irradiation light, indicating that CdSe particles were photoetched to smaller ones until the irradiated photons were not absorbed by the photoetched particles and that the SiO2 shell layer surrounding the CdSe core prevented coalescence between the photoetched particles. Although as-prepared SiO2/CdSe did not exhibit photoluminescence, the application of size-selective photoetching to SiO2/CdSe resulted in the development of the band gap emission, with the degree being enhanced with progress of the photoetching. The peak wavelength of photoluminescence decreased with a decrease in the wavelength used for the photoetching, so that the luminescence color could be tuned between red and blue. Partial photoetching of SiO2/CdSe nanoparticle films produced intense band gap emission of CdSe at the photoetched area, while the remainder of the SiO2/CdSe films did not exhibit detectable photoluminescence, resulting in the formation of a clear photoluminescence image under UV irradiation. This technique makes it possible to produce a multicolored photoluminescence image by irradiation with monochromatic lights having various wavelengths using a single source material.