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Abstract Raman spectroscopy is used to investigate the absorption and dispersion of zearalenone (ZEN) and its derivatives. The C=C stretching vibration modes of ZEN and zearalenol (ZENOL) were appeared at 975–990 cm−1. The C=O vibration mode was present at 1680–1690 cm−1 for ZEN and zearalanone (ZAN), but it was absent for ZENOL and zearalanol (ZANOL) which have –OH group instead of –C=O group in ZEN and ZAN molecular structures. On the basis of this characterization, Raman spectra of specific chemical groups and linkages corresponding to the structural difference of ZEN and its derivatives were identified. These results indicated that Raman spectroscopy can apply for the identification of ZEN and its derivatives and has a potential for the non-destructive rapid detection of these compounds in food.

We generated a human induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells isolated from a 59-year-old male patient with Alzheimer’s disease (AD). The iPSC line was meticulously characterized to confirm its pluripotency, absence of transgenes, and normal karyotype. The unexpected discovery of the M232R variant in PRNP makes this cell line a valuable resource for investigating AD pathogenesis.

Modern medicine has allowed for many advances in neurological and neurodegenerative disease (ND). However, the number of patients suffering from brain diseases is ever increasing and the treatment of brain diseases remains an issue, as drug efficacy is dramatically reduced due to the existence of the unique vascular structure, namely the blood–brain barrier (BBB). Several approaches to enhance drug delivery to the brain have been investigated but many have proven to be unsuccessful due to limited transport or damage induced in the BBB. Alternative approaches to enhance molecular delivery to the brain have been revealed in recent studies through the existence of molecular delivery pathways that regulate the passage of peripheral molecules. In this review, we present recent advancements of the basic research for these delivery pathways as well as examples of promising ventures to overcome the molecular hurdles that will enhance therapeutic interventions in the brain and potentially save the lives of millions of patients.

Abstract Background Butane is an aliphatic hydrocarbon used in various commercial products. While numerous reports of sudden cardiac-related deaths from butane inhalation have been described, butane-associated acute encephalopathy has rarely been reported. Case presentation A 38-year-old man presented with cognitive dysfunction after butane gas inhalation. Neuropsychological test results showed impairments in verbal and visual memory, and frontal executive function. Diffusion weighted MRI revealed symmetric high-signal changes in the bilateral hippocampus and globus pallidus. FDG-PET demonstrated decreased glucose metabolism in the bilateral precuneus and occipital areas and the left temporal region. At the 8-month follow-up, he showed still significant deficits in memory and frontal functions. Diffuse cortical atrophy with white matter hyperintensities and extensive glucose hypometabolism were detected on follow-up MRI and FDG-PET, respectively. Brain autopsy demonstrated necrosis and cavitary lesions in the globus pallidus. Conclusions Only a few cases of butane encephalopathy have been reported to date. Brain lesions associated with butane encephalopathy include lesions in the bilateral thalamus, insula, putamen, and cerebellum. To the best of our knowledge, this is the first report on bilateral hippocampal and globus pallidal involvement in acute butane encephalopathy. The pathophysiology of central nervous system complications induced by butane intoxication is not yet fully understood. However, the direct toxic effects of butane or anoxic injury secondary to cardiac arrest or respiratory depression have been suggested as possible mechanisms of edematous changes in the brain after butane intoxication.

Mutations in the manganese transporter gene SLC39A14 lead to inherited disorders of manganese metabolism. Chelation therapy with edetate calcium disodium (SLC39A14 deficiencyTA) is known to effectively reduce manganese deposition. We describe the first identified Korean case of SLC39A14-associated manganism and the treatment response to a 5-year chelation therapy. An 18-year-old female presented with childhood-onset dystonia. Magnetic resonance imaging showed T1 hyperintensity throughout the basal ganglia, brainstem, cerebellum, cerebral and cerebellar white matter, and pituitary gland. Blood manganese levels were elevated, and whole-exome sequencing revealed compound heterozygous mutations in SLC39A14. Treatment with intravenous CaNa2EDTA led to a significant reduction in serum manganese levels and T1 hyperintensities. However, her dystonia improved insignificantly. Hence, early diagnosis of this genetic disorder is essential because it is potentially treatable. Even though our treatment did not significantly reverse the establish deficits, chelation therapy could have been more effective if it was started at an earlier stage of the disease.

The hiPSC line was generated from peripheral blood mononuclear cells (PBMCs) collected from a female patient with young onset Parkinson’s disease (PD), carrying on heterozygous c.1448 T > C (L483P), c1483 G > C (A495P) and c.1497 G > C (V499V) mutations in the GBA gene. The PBMCs was reprogrammed into an induced pluripotent stem cell (iPSC) line (GBA PD8 or PNUSCRi004-A hiPSCs) using non-integrative Sendai virus. The cell line, PNUSCRi004-A displayed a normal karyotype and expression of pluripotency markers capable of producing derivatives of three germ layers (Ectoderm, Endoderm and Mesoderm).

Most sexual organisms ensure that organelles are inherited from a single parent. Here, the authors describe OTU2p, a Chlamydomonas deubiquitinase that drives uniparental organelle inheritance without gametic dimorphism by preventing proteasome-mediated degradation exclusively in gametes of the plus mating type.

Abstract We experimentally demonstrated that heat-dissipation power driven by ferromagnetic resonance (FMR) in superparamagnetic nanoparticles of ferrimagnetic MFe2O4 (M = Fe, Mn, Ni) gives rise to highly localized incrementation of targeted temperatures. The power generated thereby is extremely high: two orders of magnitude higher than that of the conventional Néel-Brownian model. From micromagnetic simulation and analytical derivation, we found robust correlations between the temperature increment and the intrinsic material parameters of the damping constant as well as the saturation magnetizations of the nanoparticles’ constituent materials. Furthermore, the magnetization–dissipation-driven temperature increments were reliably manipulated by extremely low strengths of applied AC magnetic fields under resonance field conditions. Our experimental results and theoretical formulations provide for a better understanding of the effect of FMR on the efficiency of heat generation as well as straightforward guidance for the design of advanced materials for control of highly localized incrementation of targeted temperatures using magnetic particles in, for example, magnetic hyperthermia bio-applications.

Semi-supervised learning (SSL) methods for classification tasks exhibit a significant performance gain because they combine regularization and pseudo-labeling methods. General pseudo-labeling methods only depend on the model’s prediction when assigning pseudo-labels, but this approach often leads to the generation of incorrect pseudo-labels, due to the network being biased toward easy classes or to the presence of confusing samples in the training set, which further decreases model performance. To address this issue, we propose a novel pseudo-labeling framework that dramatically reduces the ambiguity of pseudo-labels for confusing samples in SSL. We operate our method, called Pruning for Pseudo-Label (P-PseudoLabel), using the Easy-to-Forget (ETF) Sample Finder, which compares the outputs of the model and the pruned model to identify confusing samples. Next, we perform negative learning using the confusing samples to decrease the risk of providing incorrect information and to improve performance. Our method achieves better performance than those of recent state-of-the-art SSL methods on the CIFAR-10, CIFAR-100, and Mini-ImageNet datasets, and is on par with the state-of-the-art methods on SVHN and STL-10.

The hiPSC line was generated from peripheral blood mononuclear cells (PBMCs) collected by a male patient with young onset Parkinson’s disease, carrying on heterozygous c.680 A > G (N227S) mutation in the GBA gene. The PBMCs was reprogrammed into an induced pluripotent stem cell (iPSC) line (PNUSCRi001-A hiPSCs) using non-integrative sendai virus. The hiPSC line, PNUSCRi001-A displayed a normal karyotype and the Expression of pluripotency markers that is capable of producing derivatives of three germ layers (Ectoderm, Endoderm and Mesoderm).

Mutation in the glucocerebrosidase encoding gene 1 (GBA) is one of the most frequent causes of Parkinson’s disease (PD). Herein, we obtained peripheral blood mononuclear cells (PBMCs) from a patient with PD with a heterozygous c.475C > T (p.R159W) mutation in the GBA gene, and generated an induced pluripotent stem cell (iPSC) line (GBA PD9 or PNUSCRi002-A hiPSCs) using a non-integrative Sendai virus. The iPSC line expressed pluripotency markers (OCT4, NANOG, SSEA-4, TRA-1-60) and displayed differentiation properties in the three germ layers (ectoderm, endoderm, and mesoderm). Additionally, the patient had a normal karyotype.

An artificial synapse is an essential element to construct a hardware‐based artificial neural network (ANN). While various synaptic devices have been proposed along with studies on electrical characteristics and proper applications, a small number of conductance states with nonlinear and asymmetric conductance changes have been problematic and imposed limits on computational performance. Their applications are thus still limited to the classification of simple images or acoustic datasets. Herein, a polymer electrolyte‐gated synaptic transistor (pEGST) is demonstrated for video‐based learning and inference using transfer learning. In particular, abnormal car detection (ACD) is attempted with video‐based learning and inference to avoid traffic accidents. The pEGST showed multiple states of 8,192 (=13 bits) for weight modulation with linear and symmetric conductance changes and helped reduce the error rate to 3% to judge whether a car in a video is abnormal.

Abstract The magneto-thermal effect, which represents the conversion of magnetostatic energy to heat from magnetic materials, has been spotlighted for potential therapeutic usage in hyperthermia treatments. However, the realization of its potential has been challenged owing to the limited heating from the magnetic nanoparticles. Here, we explored a new-concept of magneto-thermal modality marked by low-power-driven, fast resonant spin-excitation followed by consequent energy dissipation, which concept has yet to be realized for current hyperthermia applications. We investigated the effect of spin resonance-mediated heat dissipation using superparamagnetic Fe3O4 nanoparticles and achieved an extraordinary initial temperature increment rate of more than 150 K/s, which is a significant increase in comparison to that for the conventional magnetic heat induction of nanoparticles. This work would offer highly efficient heat generation and precision wireless controllability for realization of magnetic-hyperthermia-based medical treatment.

Abstract Abnormal iron accumulation around the substantia nigra (SN) is a diagnostic indicator of Parkinsonism. This study aimed to identify iron-related microarchitectural changes around the SN of brains with progressive supranuclear palsy (PSP) via postmortem validations and in vivo magnetic resonance imaging (MRI). 7 T high-resolution MRI was applied to two postmortem brain tissues, from one normal brain and one PSP brain. Histopathological examinations were performed to demonstrate the molecular origin of the high-resolution postmortem MRI findings, by using ferric iron staining, myelin staining, and two-dimensional laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging. In vivo iron-related MRI was performed on five healthy controls, five patients with Parkinson’s disease (PD), and five patients with PSP. In the postmortem examination, excessive iron deposition along the myelinated fiber at the anterior SN and third cranial nerve (oculomotor nerve) fascicles of the PSP brain was verified by LA-ICP-MS. This region corresponded to those with high R 2 * values and positive susceptibility from quantitative susceptibility mapping (QSM), but was less sensitive in Perls’ Prussian blue staining. In in vivo susceptibility-weighted imaging, hypointense pixels were observed in the region between the SN and red nucleus (RN) in patients with PSP, but not in healthy controls and patients with PD. R 2 * and QSM values of such region were significantly higher in patients with PSP compared to those in healthy controls and patients with PD as well (vs. healthy control: p = 0.008; vs. PD: p = 0.008). Thus, excessive iron accumulation along the myelinated fibers at the anterior SN and oculomotor nerve fascicles may be a pathological characteristic and crucial MR biomarker in a brain with PSP.

Abstract The macroscopic properties of permanent magnets and the resultant performance required for real implementations are determined by the magnets’ microscopic features. However, earlier micromagnetic simulations and experimental studies required relatively a lot of work to gain any complete and comprehensive understanding of the relationships between magnets’ macroscopic properties and their microstructures. Here, by means of supervised learning, we predict reliable values of coercivity (μ 0 H c ) and maximum magnetic energy product (BH max) of granular NdFeB magnets according to their microstructural attributes (e.g. inter-grain decoupling, average grain size, and misalignment of easy axes) based on numerical datasets obtained from micromagnetic simulations. We conducted several tests of a variety of supervised machine learning (ML) models including kernel ridge regression (KRR), support vector regression (SVR), and artificial neural network (ANN) regression. The hyper-parameters of these models were optimized by a very fast simulated annealing (VFSA) algorithm with an adaptive cooling schedule. In our datasets of randomly generated 1,000 polycrystalline NdFeB cuboids with different microstructural attributes, all of the models yielded similar results in predicting both μ 0 H c and BH max. Furthermore, some outliers, which deteriorated the normality of residuals in the prediction of BH max, were detected and further analyzed. Based on all of our results, we can conclude that our ML approach combined with micromagnetic simulations provides a robust framework for optimal design of microstructures for high-performance NdFeB magnets.

Low serum progranulin (PGRN) is known to be associated with granulin (GRN) gene mutation and T alleles of GRN rs5848 polymorphism. However, there have been only a few Asian studies exploring these. We investigated the serum PGRN levels, rs5848 genotypes, and their relations with cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers in the Korean population. Serum PGRN levels, GRN rs5848 polymorphism, and GRN mutations were evaluated in 239 participants (22 cognitively unimpaired participants and 217 patients with neurodegenerative diseases). CSF AD biomarkers were also evaluated in 214 participants. There was no significant difference in the serum PGRN levels among the diagnostic groups. We could not find any GRN mutation carrier in our sample. The differences in the frequencies of the rs5848 genotypes among the clinical groups or the effects of the rs5848 genotypes on serum PGRN were not observed. There was no correlation between the serum PGRN level or rs5848 genotype and CSF AD biomarkers. Neither the T allele nor the TT genotype had an effect on the development of AD. Our results showed that serum PGRN levels were not associated with rs5848 genotypes, indicating that multiple single nucleotide polymorphisms might affect PGRN concentrations in an ethnicity-specific manner.

Abstract An intact cell wall is critical for cellular interactions with the environment and protecting the cell from environmental challenges. Signaling mechanisms are necessary to monitor cell wall integrity and to regulate cell wall production and remodeling during growth and division cycles. The green alga, Chlamydomonas, has a proteinaceous cell wall of defined structure that is readily removed by gametolysin (g-lysin), a metalloprotease released during sexual mating. Naked cells treated with g-lysin induce the mRNA accumulation of >100 cell wall-related genes within an hour, offering a system to study signaling and regulatory mechanisms for de novo cell wall assembly. Combining quantitative RT-PCR and luciferase reporter assays to probe transcript accumulation and promoter activity, we revealed that up to 500-fold upregulation of cell wall-related genes was driven at least partly by transcriptional activation upon g-lysin treatment. To investigate how naked cells trigger this rapid transcriptional activation, we tested whether osmotic stress and cell wall integrity are involved in this process. Under a constant hypotonic condition, comparable levels of cell wall-gene activation were observed by g-lysin treatment. In contrast, cells in an iso- or hypertonic condition showed up to 80% reduction in the g-lysin-induced gene activation, suggesting that osmotic stress is required for full-scale responses to g-lysin treatment. To test whether mechanical perturbation of cell walls is involved, we isolated and examined a new set of cell wall mutants with defective or little cell walls. All cell wall mutants examined showed a constitutive upregulation of cell wall-related genes at a level that is only achieved by treatment with g-lysin in wild-type cells. Our study suggests a cell wall integrity monitoring mechanism that senses both osmotic stress and mechanical defects of cell walls and regulates cell wall-gene expression in Chlamydomonas, which may relate to cell wall integrity signaling mechanisms in other organisms.

Artificial intelligence (AI) techniques can be a solution for delayed or misdiagnosed pneumothorax. This study developed, a deep-learning-based AI model to estimate the pneumothorax amount on a chest radiograph and applied it to a treatment algorithm developed by experienced thoracic surgeons. U-net performed semantic segmentation and classification of pneumothorax and non-pneumothorax areas. The pneumothorax amount was measured using chest computed tomography (volume ratio, gold standard) and chest radiographs (area ratio, true label) and calculated using the AI model (area ratio, predicted label). Each value was compared and analyzed based on clinical outcomes. The study included 96 patients, of which 67 comprised the training set and the others the test set. The AI model showed an accuracy of 97.8%, sensitivity of 69.2%, a negative predictive value of 99.1%, and a dice similarity coefficient of 61.8%. In the test set, the average amount of pneumothorax was 15%, 16%, and 13% in the gold standard, predicted, and true labels, respectively. The predicted label was not significantly different from the gold standard (p = 0.11) but inferior to the true label (difference in MAE: 3.03%). The amount of pneumothorax in thoracostomy patients was 21.6% in predicted cases and 18.5% in true cases.

Abstract Background Complex multicellularity requires elaborate developmental mechanisms, often based on the versatility of heterodimeric transcription factor (TF) interactions. Homeobox TFs in the TALE superclass are deeply embedded in the gene regulatory networks that orchestrate embryogenesis. Knotted-like homeobox (KNOX) TFs, homologous to animal MEIS, have been found to drive the haploid-to-diploid transition in both unicellular green algae and land plants via heterodimerization with other TALE superclass TFs, demonstrating remarkable functional conservation of a developmental TF across lineages that diverged one billion years ago. Here, we sought to delineate whether TALE-TALE heterodimerization is ancestral to eukaryotes. Results We analyzed TALE endowment in the algal radiations of Archaeplastida, ancestral to land plants. Homeodomain phylogeny and bioinformatics analysis partitioned TALEs into two broad groups, KNOX and non-KNOX. Each group shares previously defined heterodimerization domains, plant KNOX-homology in the KNOX group and animal PBC-homology in the non-KNOX group, indicating their deep ancestry. Protein-protein interaction experiments showed that the TALEs in the two groups all participated in heterodimerization. Conclusions Our study indicates that the TF dyads consisting of KNOX/MEIS and PBC-containing TALEs must have evolved early in eukaryotic evolution. Based on our results, we hypothesize that in early eukaryotes, the TALE heterodimeric configuration provided transcription-on switches via dimerization-dependent subcellular localization, ensuring execution of the haploid-to-diploid transition only when the gamete fusion is correctly executed between appropriate partner gametes. The TALE switch then diversified in the several lineages that engage in a complex multicellular organization.

In recent studies, iron overload has been reported in atypical parkinsonian syndromes. The topographic patterns of iron distribution in deep brain nuclei vary by each subtype of parkinsonian syndrome, which is affected by underlying disease pathologies. In this study, we developed a novel framework that automatically analyzes the disease-specific patterns of iron accumulation using susceptibility weighted imaging (SWI). We constructed various machine learning models that can classify diseases using radiomic features extracted from SWI, representing distinctive iron distribution patterns for each disorder. Since radiomic features are sensitive to the region of interest, we used a combination of T1-weighted MRI and SWI to improve the segmentation of deep brain nuclei. Radiomics was applied to SWI from 34 patients with a parkinsonian variant of multiple system atrophy, 21 patients with cerebellar variant multiple system atrophy, 17 patients with progressive supranuclear palsy, and 56 patients with Parkinson’s disease. The machine learning classifiers that learn the radiomic features extracted from iron-reflected segmentation results produced an average area under receiver operating characteristic curve (AUC) of 0.8607 on the training data and 0.8489 on the testing data, which is superior to the conventional classifier with segmentation using only T1-weighted images. Our radiomic model based on the hybrid images is a promising tool for automatically differentiating atypical parkinsonian syndromes.

Most neurodegeneration with brain iron accumulation (NBIA) disorders can be distinguished by identifying characteristic changes on magnetic resonance imaging (MRI) in combination with clinical findings. However, a significant number of patients with an NBIA disorder confirmed by genetic testing have MRI features that are atypical for their specific disease. The appearance of specific MRI patterns depends on the stage of the disease and the patient's age at evaluation. MRI interpretation can be challenging because of heterogeneously acquired MRI datasets, individual interpreter bias, and lack of quantitative data. Therefore, optimal acquisition and interpretation of MRI data are needed to better define MRI phenotypes in NBIA disorders. The stepwise approach outlined here may help to identify NBIA disorders and delineate the natural course of MRI-identified changes.

Visualizing gradual changes in neuromelanin distribution within the substantia nigra is an important metric used to monitor the progression of Parkinsonism. This study aimed to identify the origin of the mismatch region between magnetic resonance transverse relaxation times (T2 and T2*) in the substantia nigra and investigate its feasibility and implications for in vivo detection of neuromelanin as a clinical biomarker. The relationships between neuromelanin distribution assessed by histological staining and the area of T2 and T2* mismatch determined by high- and low-resolution magnetic resonance relaxometry at 7T were directly compared in two normal and one depigmented substantia nigra collected at postmortem. In vivo feasibility of assessing T2 and T2* mismatch, clinically, was investigated using 3T magnetic resonance imaging. In the normal postmortem substantia nigra tissue, the T2 and T2* mismatch region exhibiting a linear pattern was strongly colocalized with neuromelanin distribution along the dorsal substantia nigra pars compacta, but a negligible amount of dorsal mismatch was observed in the depigmented brain. The regions of T2 and T2* mismatch from MRI, neuromelanin pigments from histology, and elevated iron signals from mass spectrometry were spatially overlapped for a normal postmortem brain. In preliminary in vivo studies, a similar, linear T2 and T2* mismatch region was observed in the dorsal area of the substantia nigra in eight normal subjects; this mismatch was significantly obscured in eight Parkinson’s disease patients. The length of the dorsal linear mismatch line based on the T2*-T2 mask was significantly shorter in the Parkinson’s disease patients compared to normal controls; this result was corroborated by reduced striatal uptake of [18F] FP-CIT dopamine transporters assessed by positron emission tomography scans. In conclusion, the measurement of T2 and T2* mismatch could serve as a complementary imaging biomarker to visualize the dorsal region of the substantia nigra pars compacta, which contains large amounts of neuromelanin.

Objective Autonomic symptoms are commonly observed in patients with Parkinson’s disease (PD) and often limit the activities of daily living. The Scale for Outcomes in Parkinson’s disease-Autonomic (SCOPA-AUT) was developed to evaluate and quantify autonomic symptoms in PD. The goal of this study was to translate the original SCOPA-AUT, which was written in English, into Korean and to evaluate its reliability and validity for Korean PD patients. Methods For the translation, the following processes were performed: forward translation, backward translation, expert review, pretest of the pre-final version and development of the final Korean version of SCOPA-AUT (K-SCOPA-AUT). In total, 127 patients with PD from 31 movement disorder clinics of university-affiliated hospitals in Korea were enrolled in this study. All patients were assessed using the K-SCOPA-AUT and other motor, non-motor, and quality of life scores. Test-retest reliability for the K-SCOPA-AUT was assessed over a time interval of 10−14 days. Results The internal consistency and reliability of the K-SCOPA-AUT was 0.727 as measured by the mean Cronbach’s α-coefficient. The test-retest correlation reliability was 0.859 by the Guttman split-half coefficient. The total K-SCOPA-AUT score showed a positive correlation with other non-motor symptoms [the Korean version of non-motor symptom scale (K-NMSS)], activities of daily living (Unified Parkinson’s Disease Rating Scale part II) and quality of life [the Korean version of Parkinson’s Disease Quality of Life 39 (K-PDQ39)]. Conclusion The K-SCOPA-AUT had good reliability and validity for the assessment of autonomic dysfunction in Korean PD patients. Autonomic symptom severities were associated with many other motor and non-motor impairments and influenced quality of life.

Objectives: To validate a visual rating scale reflecting sub-regional patterns of putaminal hypointensity in susceptibility-weighted imaging of patients with multiple system atrophy (MSA).Methods: Using a visual rating scale (from G0 to G3), 2 examiners independently rated putaminal hypointensities of 37 MSA patients and 21 control subjects. To investigate the correlation with the scales, R2* values and the volume of the entire putamen were measured.Results: MSA patients with parkinsonian variant had significantly higher scores than those with cerebellar variant. Visual rating scores in MSA were correlated with R2* values [General estimating equation (GEE), Wald chi-square = 25.89, corrected p < 0.001] and volume (Wald chi-square = 75.44, corrected p < 0.001). They correlated with UPDRS motor scores. Binary logistic regression analyses revealed that the visual rating scale was a significant predictor for discriminating MSA patients from controls [multivariate model adjusted for age and sex, odds ratio 52.722 (corrected p = 0.009)]. Pairwise comparison between areas under the curve (AUCs) revealed that the visual rating scale demonstrated higher accuracy than R2* values [difference between AUCs; univariate model = 0.247 (corrected p < 0.001); multivariate model = 0.186 (corrected p = 0.003)]. There were no significant differences in clinical characteristics between the high-iron group, defined as putamen with visual rating scale ≥ G2 and R2* values ≥ third quartile, and the remaining patients.Conclusion: The visual rating scale, which reflects quantitative iron content and atrophy of the putamen as well as motor severities, could be useful for the discrimination and evaluation of patients with MSA.

Recent data suggest mechanistic links among perturbed iron homeostasis, oxidative stress, and misfolded protein aggregation in neurodegenerative diseases. Iron overload and toxicity toward dopaminergic neurons have been established as playing a role in the pathogenesis of Parkinson's disease (PD). Brain iron accumulation has also been documented in atypical parkinsonian syndromes (APS), mainly comprising multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Iron-sensitive magnetic resonance imaging (MRI) has been applied to identify iron-related signal changes for the diagnosis and differentiation of these disorders. Topographic patterns of widespread iron deposition in deep brain nuclei have been described as differing between patients with MSA and PSP and those with PD. A disease-specific increase of iron occurs in the brain regions mainly affected by underlying disease pathologies. However, whether iron changes are a primary pathogenic factor or an epiphenomenon of neuronal degeneration has not been fully elucidated. Moreover, the clinical implications of iron-related pathology in APS remain unclear. In this review study, we collected data from qualitative and quantitative MRI studies on brain iron accumulation in APS to identify disease-related patterns and the potential role of iron-sensitive MRI.

ABSTRACT Animals and amoebae assemble actin/spectrin-based plasma membrane skeletons, forming what is often called the cell cortex, whereas euglenids and alveolates (ciliates, dinoflagellates, and apicomplexans) have been shown to assemble a thin, viscoelastic, actin/spectrin-free membrane skeleton, here called the epiplast. Epiplasts include a class of proteins, here called the epiplastins, with a head/medial/tail domain organization, whose medial domains have been characterized in previous studies by their low-complexity amino acid composition. We have identified two additional features of the medial domains: a strong enrichment of acid/base amino acid dyads and a predicted β-strand/random coil secondary structure. These features have served to identify members in two additional unicellular eukaryotic radiations—the glaucophytes and cryptophytes—as well as additional members in the alveolates and euglenids. We have analyzed the amino acid composition and domain structure of 219 epiplastin sequences and have used quick-freeze deep-etch electron microscopy to visualize the epiplasts of glaucophytes and cryptophytes. We define epiplastins as proteins encoded in organisms that assemble epiplasts, but epiplastin-like proteins, of unknown function, are also encoded in Insecta, Basidiomycetes, and Caulobacter genomes. We discuss the diverse cellular traits that are supported by epiplasts and propose evolutionary scenarios that are consonant with their distribution in extant eukaryotes. IMPORTANCE Membrane skeletons associate with the inner surface of the plasma membrane to provide support for the fragile lipid bilayer and an elastic framework for the cell itself. Several radiations, including animals, organize such skeletons using actin/spectrin proteins, but four major radiations of eukaryotic unicellular organisms, including disease-causing parasites such as Plasmodium, have been known to construct an alternative and essential skeleton (the epiplast) using a class of proteins that we term epiplastins. We have identified epiplastins in two additional radiations and present images of their epiplasts using electron microscopy. We analyze the sequences and secondary structure of 219 epiplastins and present an in-depth overview and analysis of their known and posited roles in cellular organization and parasite infection. An understanding of epiplast assembly may suggest therapeutic approaches to combat infectious agents such as Plasmodium as well as approaches to the engineering of useful viscoelastic biofilms.

Objective Neurodegeneration with brain iron accumulation (NBIA) represents a group of inherited movement disorders characterized by iron accumulation in the basal ganglia. Recent advances have included the identification of new causative genes and highlighted the wide phenotypic variation between and within the specific NBIA subtypes. This study aimed to investigate the current status of NBIA in Korea. Methods We collected genetically confirmed NBIA patients from twelve nationwide referral hospitals and from a review of the literature. We conducted a study to describe the phenotypic and genotypic characteristics of Korean adults with atypical pantothenate kinase-associated neurodegeneration (PKAN). Results Four subtypes of NBIA including PKAN (n = 30), PLA2G6-related neurodegeneration (n = 2), beta-propeller protein-associated neurodegeneration (n = 1), and aceruloplasminemia (n = 1) have been identified in the Korean population. The clinical features of fifteen adults with atypical PKAN included early focal limb dystonia, parkinsonism-predominant feature, oromandibular dystonia, and isolated freezing of gait (FOG). Patients with a higher age of onset tended to present with parkinsonism and FOG. The p.R440P and p.D378G mutations are two major mutations that represent approximately 50% of the mutated alleles. Although there were no specific genotype-phenotype correlations, most patients carrying the p.D378G mutation had a late-onset, atypical form of PKAN. Conclusions We found considerable phenotypic heterogeneity in Korean adults with atypical PKAN. The age of onset may influence the presentation of extrapyramidal symptoms.

Luminescent nanoparticles have reached a high level of maturity in materials and spectral tunability for optics and optoelectronics. However, the lack of facile methodology for heterojunction formation of the nanoparticles provides many challenges for scalability. In this paper we demonstrate a simple procedure to synthesize a nanoparticle-embedded polymer nanorod hybrid structure via a template-based electrochemical method using anodic aluminum oxide membranes. This method enables the formation of interactive nanostructures wherein the interface area between the two components is maximized. As a proof of concept, semiconducting CdSe nanoparticles were embedded in polypyrrole nanorods with dimensions that can be finely tuned. We observed enhanced photoluminescence of the hybrid structures compared with bare polypyrrole nanorods.

Upon publication of the original article [1], it was noticed that Alexandra Z. Worden’s affiliation is not complete. The full affiliation information for Alexandra Z. Worden is can be found below and in the complete affiliation list of this Correction article.

Studies investigating the impact of white matter hyperintensities (WMHs) on the response of acetylcholinesterase inhibitors in patients with Alzheimer's disease (AD) have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs.Three hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog) from the baseline to the end of the study.Of the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 136; group 2, n = 46) during the 24-week study period. Demographic factors did not differ between group 1 and group 2. There were no significant differences in change in ADAS-cog between group 1 (-0.62±5.70) and group 2 (-0.23±5.98) after the 24-week rivastigmine patch therapy (p = 0.378). The patients in group 1 had a 0.63-point improvement from baseline on the Frontal Assessment Battery, while group 2 had a 0.16-point decline compared to baseline at the end of the study (p = 0.037). The rates of adverse events (AEs) (42.6 vs. 40.3%) and discontinuation due to AEs (10.3% vs. 4.3%) did not differ between the groups.Although the efficacy and tolerability of rivastigmine patch therapy were not associated with WMH severity in patients with AD, some improvement in frontal function was observed in those with minimal WMHs.ClinicalTrials.gov NCT01380288.

Background and Purpose Susceptibility-weighted imaging (SWI) has been shown to be superior in its ability to demonstrate brain mineralization than other conventional MR imaging. The goal of our study was therefore to assess the frequency and extent of putaminal hypointensity in parkinsonian variant MSA using SWI. Methods 11 patients with multiple system atrophy-parkinsonian type (MSA-p), 30 patients with Parkinson’s disease (PD), and age matched 30 controls were investigated using 3 Tesla MRI. The pattern of putaminal hypointensity was measured using a visual grading scale and scored from 0 to 3. Results Hemi- or bilateral putaminal hypointensity (a score of ≥ 2) and hyperintense rim were recognized in 81.8% and 54.5% of 11 MSA-p, respectively. The scores of putaminal hypointensity of MSA-p were significantly higher than other groups (p < 0.001), a score of ≥ 2 differentiated MSA-p from other groups. And all five patients with early disease stage also showed these characteristic findings. Conclusions SWI appears to be useful for depicting putaminal hypointensity even in early stage of MSA-p. This finding suggests that iron deposition associated putaminal degeneration can occur early in the disease process.

BACKGROUND:Uric acid (UA) is an endogenous antioxidant which is known to reduce oxidative stress and also chelate iron ion. Recent studies have provided evidence that UA may play a neuroprotective role in Parkinson's disease (PD). However, it is unknown whether UA relates to nigral iron deposition, which is a characteristic pathophysiological alteration in PD. The aim of this study was to determine the potential relationship of these two markers in patients with PD. METHODS:A total of 30 patients of PD and 25 age- and gender- matched healthy controls underwent 3-Tesla MRI and laboratory tests including serum UA levels. We assessed iron levels by measuring phase shift values using susceptibility-weighted image. Mean phase shift values of the substantia nigra (SN), red nucleus, head of the caudate nucleus, globus pallidus, putamen, thalamus, and frontal white matter were calculated and correlated with serum UA levels. RESULTS:Serum UA levels were significantly decreased in the PD patients than in the controls. Phase shift values in bilateral SN were significantly increased in the PD patients than in the controls. There was no significant correlation between serum UA levels and nigral phase shift values. CONCLUSIONS:As previous studies, low serum UA level and increased nigral iron content in the PD was reconfirmed in this study. However, we failed to find the relationship between these two markers. Our data suggest that serum UA may not be important determinant of nigral iron deposition in PD.

Dystonic head tremor is known to be a feature in some patients with DYT1 mutation. However, isolated tremor of the head without relevant cervical dystonia has rarely been described. We report here a patient with the three-bp GAG deletion in the DYT1 gene (904_906delGAG) who had severe head tremor in the frame of a generalized limb dystonia.

BackgroundStudies of secondary movement disorder (MD) caused by cerebrovascular diseases have primarily focused on post-stroke MD. However, MD can also result from cerebral artery stenosis (CAS) without clinical manifestations of stroke. In this study, we aimed to investigate the clinical characteristics of MD associated with CAS.Materials and MethodsA nationwide multicenter retrospective analysis was performed based on the data from patients with CAS-associated MDs from 16 MD specialized clinics in South Korea, available between January 1999 and September 2019. CAS was defined as the >50% luminal stenosis of the major cerebral arteries. The association between MD and CAS was determined by MD specialists using pre-defined clinical criteria. The collected clinical information included baseline demographics, features of MD, characteristics of CAS, treatment, and MD outcomes. Statistical analyses were performed to identify factors associated with the MD outcomes.ResultsThe data from a total of 81 patients with CAS-associated MD were analyzed. The mean age of MD onset was 60.5 ± 19.7 years. Chorea was the most common MD (57%), followed by tremor/limb-shaking, myoclonus, and dystonia. Atherosclerosis was the most common etiology of CAS (78%), with the remaining cases attributed to moyamoya disease (MMD). Relative to patients with atherosclerosis, those with MMD developed MD at a younger age (p < 0.001) and had a more chronic mode of onset (p = 0.001) and less acute ischemic lesion (p = 0.021). Eight patients who underwent surgical treatment for CAS showed positive outcomes. Patients with acute MD onset had a better outcome than those with subacute-to-chronic MD onset (p = 0.008).ConclusionsThis study highlights the spectrum of CAS-associated with MD across the country. A progressive, age-dependent functional neuronal modulation in the basal ganglia due to CAS may underlie this condition.