Abstract
Highly crystalline single-domain magnetite Fe
3
O
4
nanoparticles (NPs) are important, not only for fundamental understanding of magnetic behaviour, but also for their considerable potential ...applications in biomedicine and industry. Fe
3
O
4
NPs with sizes of 10–300 nm were systematically investigated to reveal the fundamental relationship between the crystal domain structure and the magnetic properties. The examined Fe
3
O
4
NPs were prepared under well-controlled crystal growth conditions using a large-scale liquid precipitation method. The crystallite size of cube-like NPs estimated from X-ray diffraction pattern increased linearly as the particle size (estimated by transmission electron microscopy) increased from 10 to 64.7 nm, which indicates that the NPs have a single-domain structure. This was further confirmed by the uniform lattice fringes. The critical size of approximately 76 nm was obtained by correlating particle size with both crystallite size and magnetic coercivity; this was reported for the first time in this study. The coercivity of cube-like Fe
3
O
4
NPs increased to a maximum of 190 Oe at the critical size, which suggests strong exchange interactions during spin alignment. Compared with cube-like NPs, sphere-like NPs have lower magnetic coercivity and remanence values, which is caused by the different orientations of their polycrystalline structure.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Alzheimer's disease (AD) is the most common form of dementia, characterized by accumulation of amyloid β (Aβ) and neurofibrillary tangles. Oxidative stress and inflammation are considered to play an ...important role in the development and progression of AD. However, the extent to which these events contribute to the Aβ pathologies remains unclear. We performed inter-species comparative gene expression profiling between AD patient brains and the App
and 3xTg-AD-H mouse models. Genes commonly altered in App
and human AD cortices correlated with the inflammatory response or immunological disease. Among them, expression of AD-related genes (C4a/C4b, Cd74, Ctss, Gfap, Nfe2l2, Phyhd1, S100b, Tf, Tgfbr2, and Vim) was increased in the App
cortex as Aβ amyloidosis progressed with exacerbated gliosis, while genes commonly altered in the 3xTg-AD-H and human AD cortices correlated with neurological disease. The App
cortex also had altered expression of genes (Abi3, Apoe, Bin2, Cd33, Ctsc, Dock2, Fcer1g, Frmd6, Hck, Inpp5D, Ly86, Plcg2, Trem2, Tyrobp) defined as risk factors for AD by genome-wide association study or identified as genetic nodes in late-onset AD. These results suggest a strong correlation between cortical Aβ amyloidosis and the neuroinflammatory response and provide a better understanding of the involvement of gender effects in the development of AD.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•In Alzheimer’s disease (AD) brain, glucose metabolism and insulin signaling are impaired.•Mitochondrial dysfunction and oxidative stress are involved in AD pathology.•Oxidative DNA damage may be ...involved in AD pathology.
In normal brain, neurons in the cortex and hippocampus produce insulin, which modulates glucose metabolism and cognitive functions. It has been shown that insulin resistance impairs glucose metabolism and mitochondrial function, thus increasing production of reactive oxygen species. Recent progress in Alzheimer’s disease (AD) research revealed that insulin production and signaling are severely impaired in AD brain, thereby resulting in mitochondrial dysfunction and increased oxidative stress. Among possible oxidative DNA lesions, 8-oxoguanine (8-oxoG) is highly accumulated in the brain of AD patients. Previously we have shown that incorporating 8-oxoG in nuclear and mitochondrial DNA promotes MUTYH (adenine DNA glycosylase) dependent neurodegeneration. Moreover, cortical neurons prepared from MTH1 (8-oxo-dGTPase)/OGG1 (8-oxoG DNA glycosylase)-double deficient adult mouse brains is shown to exhibit significantly poor neuritogenesis in vitro with increased 8-oxoG accumulation in mitochondrial DNA in the absence of antioxidants. Therefore, 8-oxoG can be considered involved in the neurodegenerative process in AD brain. In mild cognitive impairment, mitochondrial dysfunction and oxidative damage may induce synaptic dysfunction due to energy failures in neurons thus resulting in impaired cognitive function. If such abnormality lasts long, it can lead to vicious cycles of oxidative damage, which may then trigger the neurodegenerative process seen in Alzheimer type dementia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Purpose
Conventional genetic analyzers require surgically obtained tumor tissues to confirm the molecular diagnosis of diffuse glioma. Recent technical breakthroughs have enabled increased ...utilization of cell-free tumor DNA (ctDNA) in body fluids as a reliable resource for molecular diagnosis in various cancers. Here, we tested the application of a chip-based digital PCR system for the less invasive diagnosis (i.e., liquid biopsy) of diffuse glioma using the cerebrospinal fluid (CSF).
Methods
CSF samples from 34 patients with diffuse glioma were collected from the surgical field during craniotomy. Preoperative lumbar CSF collection was also performed in 11 patients. Extracted ctDNA was used to analyze diagnostic point mutations in
IDH1
R132H,
TERT
promoter (C228T and C250T), and
H3F3A
(K27M) on the QuantStudio
®
3D Digital PCR System. These results were compared with their corresponding tumor DNA samples.
Results
We detected either of the diagnostic mutations in tumor DNA samples from 28 of 34 patients. Among them, we achieved precise molecular diagnoses using intracranial CSF in 20 (71%). Univariate analyses revealed that the World Health Organization (WHO) grade (p = 0.0034), radiographic enhancement (p = 0.0006), and Mib1 index (p = 0.01) were significant predictors of precise CSF-based molecular diagnosis. We precisely diagnosed WHO grade III or IV diffuse gliomas using lumbar CSF obtained from 6 (87%) of 7 patients with tumors harboring any mutation.
Conclusion
We established a novel, non-invasive molecular diagnostic method using a chip-based digital PCR system targeting ctDNA derived from CSF with high sensitivity and specificity, especially for high-grade gliomas.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
...immunohistochemistry revealed fine granular prion protein (PrP) deposits that were focally detected in the stratified squamous epithelium and coarse granular deposits of PrP along the basal ...membrane of the esophageal mucosal epithelium of the proband case (Figure 2). ...we conducted a genetic analysis, and sequencing of the prion protein (PRNP) gene identified a Y162X truncation mutation. ...our findings suggest that PRNP truncation mutations can cause refractory esophageal achalasia.
There is great demand for nanoparticles (NPs) dispersed in liquid phases for practical applications of functional NP materials. However, it is difficult to produce NP dispersions with specific ...particle sizes, concentrations, viscosities, and purities on an industrial scale (large mass production rate and low energy consumption). In this review, we highlight recent developments in NP dispersion using low-energy bead mill. Such processes enable the use of small beads (7–50 μm). Smaller beads reduce the collision and shear energies of NPs during agitation. This minimizes NP breakage/damage, and retains the shape and crystallinity of the NPs, which determine the inherent NP functions. This review starts with a brief explanation of the theory and current status of NP dispersion and describes the mechanism and experimental results for low-energy bead mill processes, i.e., using uniaxial, dual-axial, and all-separator bead mills, and selection of dispersing agent. Applications of NP dispersions, including nanocomposite materials, and methods for dealing with NP dispersion coloration are also discussed, along with future research directions.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Our aim was to assess the diagnostic performance of intravoxel incoherent motion (IVIM) MR imaging for differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs).
Forty-five patients ...with diffuse glioma (age 50.9 ± 20.4 y; 26 males, 19 females) were assessed with IVIM imaging using 13 b-values (0-1000 s/mm(2)) at 3T. The perfusion fraction (f), true diffusion coefficient (D), and pseudo-diffusion coefficient (D*) were calculated by fitting the bi-exponential model. The apparent diffusion coefficient (ADC) was obtained with 2 b-values (0 and 1000 s/mm(2)). Relative cerebral blood volume was measured by the dynamic susceptibility contrast method. Two observers independently measured D, ADC, D*, and f, and these measurements were compared between the LGG group (n = 16) and the HGG group (n = 29).
Both D (1.26 ± 0.37 mm(2)/s in LGG, 0.94 ± 0.19 mm(2)/s in HGG; P < .001) and ADC (1.28 ± 0.35 mm(2)/s in LGG, 1.03 ± 0.19 mm(2)/s in HGG; P < .01) were lower in the HGG group. D was lower than ADC in the LGG (P < .05) and HGG groups (P < .0001). D* was not different between the groups. The f-values were significantly larger in HGG (17.5 ± 6.3%) than in LGG (5.8 ± 3.8%; P < .0001) and correlated with relative cerebral blood volume (r = 0.85; P < .0001). Receiver operating characteristic analyses showed areas under curve of 0.95 with f, 0.78 with D, 0.73 with ADC, and 0.60 with D*.
IVIM imaging is useful in differentiating HGGs from LGGs.
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► A fine bead mill technology was used for dispersing hBN nanoparticles. ► A monodispersed hBN nanoparticles suspension in a water phase was obtained. ► The (3-acryl-oxypropyl) ...trimethoxysilane (APMS) used as a dispersant. ► The surface functionalization with APMS attained suspension stability. ► The mechanism of surface functionalization with APMS was proposed.
This paper presents the surface functionalization with silane coupling agents for dispersing and stabilizing hexagonal boron nitride (hBN) nanoparticle suspension in a water phase. Fine milling using 30
μm bead technology was utilized for the reduction of particle size, while dispersing agents with silane coupling agents were used for surface modification to enhance dispersion stability. A monodispersed hBN nanoparticle was obtained by controlling the processing parameters and by optimizing the dispersant dosage. The hBN nanoparticle suspension showed a high degree of dispersion stability with a zeta potential below −40
mV when (3-acryl-oxypropyl) trimethoxysilane (APMS) was used as the dispersing agent. Under optimal operation conditions for bead milling, the final average size of the particle distribution for the hBN suspension was 46
nm and 38
nm for 0.5
wt.% and 5
wt.% hBN, respectively. In addition, the surface characteristics, morphology, crystal structure and chemical composition of the hBN particles before and after bead milling were investigated to know the effect of bead milling. Finally, the surface functionalization mechanism that enhanced the stability of hBN nanoparticle dispersion by electrosteric stabilization was also proposed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
Myotonic dystrophy type 1 (DM1) is an inherited autosomal-dominant condition that induces altered splicing of transcripts, including MAPT, leading to a distinctive abnormal deposition of tau ...protein in the CNS. We characterized the tau isoforms of abnormal depositions in the brains of 4 patients with classic DM1 by immunohistochemistry using isoform-specific antibodies. All patients, including those of presenile age, showed numerous neurofibrillary tangles (NFTs) of both 3-repeat and 4-repeat tau in the limbic area and mild involvement in the cerebral cortex. Amyloid-β deposition was only seen in 1 senile case while cortical tauopathy in all other cases was consistent with primary age-related tauopathy (PART). In the putamen and globus pallidus, only a few tau deposits were observed. Tau deposits in the brainstem frequently showed a DM1-specific pattern with 3-repeat tau dominant NFTs. Additionally, tau-positive astrocytes morphologically similar to tufted astrocytes and astrocytic plaques were occasionally observed in the brainstem; however, they were predominantly composed of 3-repeat tau. Thus, the classic DM1 showed both early onset of PART-like pathology in the limbic areas as a progeroid syndrome of DM1 and an abnormal splicing event in the brainstem leading to 3-repeat tau dominant accumulation with both neuronal and astrocytic involvement.
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