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Neuronal ceroid lipofuscinosis type1(CLN1), is a one form of the group of neuronal ceroid lipofuscinoses (NCLs), which is a neurodegenerative disorder characterized by progressive psychomotor deterioration, ataxia, epilepsy, and visual impairment. Neurological manifestations occur at a wide range of ages, from infancy to adulthood, but are most common in infancy. The prevalence of CLN1 is unclear; however, it is very rare in Japan and Europe. In Japan, only a few cases have been reported, two of infantile- and one of juvenile-onset type. Nonetheless, the clinical characteristics of Japanese patients and their relationship with the genotype have not been sufficiently investigated. Here, we report the cases of two siblings that presented with juvenile-onset (a 22-year-old man and a 29-year-old woman) CLN1 associated with type II diabetes mellitus. In both cases, visual impairment followed by learning disability was observed from school-age, and retinitis pigmentosa was noted on ophthalmological examination. These patients presented type II diabetes mellitus during their later teenage years. Brain magnetic resonance imaging (MRI) revealed marked atrophy of the cerebrum and cerebellum. The clinical symptoms lead to suspect NCLs. Decreased PPT1 enzyme activity in dried blood spot (DBS)and leukocytes were observed, and the genetic analysis revealed heterozygous missense variants in PPT1, c.550G > A/c.664 A > G (p. Glu184Lys/p. Lys216Glu). The latter variant of this patients was novel variant. The residual enzymatic activity of PPT1 in these cases is higher than that in the infantile type. CLN1 mutant cells are known to have altered subcellular expression and localization, enhanced lipid raft-mediated endocytosis, abnormal autophagy, and mitochondrial dysfunction. Although the prevalence of diabetes mellitus is high and the possibility of coincidental complications cannot be ruled out, we concluded that mitochondrial abnormalities are involved in insulin resistance and may be implicated in the development of type II diabetes mellitus. Further studies are needed to prove the correlation between CLN1 and diabetes mellitus.

Abstract Intellectual developmental disorder with dysmorphic facies, speech delay, and T-cell abnormalities (MIM # 618092) is a congenital disorder derived from pathogenic variants of the B-cell leukemia/lymphoma 11B gene (BCL11B). Several variants have been reported to date. Here, through comprehensive genomic analysis, a novel BCL11B truncation variant, NM_138576.4(BCL11B_v001): c.2439_2452dup [p.(His818Argfs*31)], was identified in a Japanese male patient with developmental delay, distinctive features, and early craniosynostosis.

Arginase deficiency is a progressive neurological disorder characterized by episodic hyperammonemia crises. Our patient had been diagnosed with cerebral palsy (spastic paraplegia) in childhood and received rehabilitation. She had suffered parotid swelling since the age of 5 years, prior to liver dysfunction becoming apparent, and then developed hyperamylasemia at 8 years of age. At age 25 years, she presented with hyperammonemia and elevations of aspartate aminotransferase and alanine aminotransferase. At age 27 years, she was diagnosed with arginase deficiency due to hyperargininemia and absent arginase activity in erythrocytes. Liver cirrhosis was also present. She was hospitalized several times for management of episodic hyperammonemia due to recurrent viral infections, an unbalanced diet, and poor compliance with medications.

The study of genetic alterations and molecular biology in central nervous system (CNS) tumors has improved the accuracy of estimations of patient prognosis and tumor categorization. Therefore, the updated 2021 World Health Organization (WHO) classification includes various diagnostic genes, molecules, and pathways for diagnosis, as well as histological findings. These findings are expected both to have diagnostic applications and to facilitate new targeted therapies that target tumor-specific genetic changes and molecular biology. Intramedullary spinal cord tumors (IMSCTs) are rare CNS tumors that are difficult to treat because they occur in eloquent areas. Although the genetic underpinnings of IMSCTs remain unclear compared to their intracranial counterparts, the genetic characteristics of these tumors are gradually being revealed. Here, we describe the major changes in the new 2021 WHO classification and review the major types of IMSCTs, with an emphasis on their clinical features and genetic alterations.

Abstract Background Saliva is often used as a biomarker for the diagnosis of some oral and systematic diseases, owing to the non‐invasive attribute of the fluid. In this study, we aimed to identify salivary biomarkers for distinguishing lung cancer (LC) from benign lung lesion (BLL). Materials and Methods Unstimulated saliva samples were collected from 41 patients with LC and 21 with BLL. Salivary metabolites were comprehensively analyzed using capillary electrophoresis mass spectrometry. To differentiate between patients with LCs and BLLs, the discriminatory ability of each biomarker was assessed. Furthermore, a multiple logistic regression (MLR) model was developed for evaluating discriminatory ability of each salivary metabolite. Results The profiles of 10 salivary metabolites were remarkably different between the LC and BLL samples. Among them, the concentration of salivary tryptophan was significantly lower in the samples from patients with LC than in those from patients with BLL, and the area under the curve (AUC) for discriminating patients with LC from those with BLL was 0.663 (95% confidence interval [CI] = 0.516–0.810, p = 0.036). Furthermore, from the MLR model developed using these metabolites, diethanolamine, cytosine, lysine, and tyrosine, were selected using the back‐selection regression method. The MLR model based on these four metabolites had a high discriminatory ability for patients with LC and those with BLL (AUC = 0.729, 95% CI = 0.598–0.861, p = 0.003). Conclusion The four salivary metabolites can serve as potential non‐invasive biomarkers for distinguishing LC from BLL.

Abstract A 9‐year‐old intact female chinchilla (Chinchilla lanigera) was presented to a referring veterinarian due to small, multiple cervical nodules that had been rapidly increasing in size and number. Cytology of the nodules revealed sheets of pleomorphic round cells that were morphologically most compatible with histiocytic sarcoma. Histologically, the nodules were fairly demarcated, partially infiltrative, densely cellular neoplasm, and was composed of pleomorphic large round cells arranged in sheets. Special stains for bacteria (Gram stain and Ziehl–Neelsen stain) and fungi (periodic acid‐Schiff stain) were all negative. On immunohistochemistry, the neoplastic cells showed strong cytoplasmic positivity for Iba‐1 and CD204, but were negative for CD3 and CD20. Transmission electron microscopy failed to detect Birbeck's granules in the cytoplasm of the neoplastic histiocytes. The chinchilla received chemotherapy with lomustine but died spontaneously on day 62 despite treatment. Autopsy with histopathologic examination revealed disseminated histiocytic sarcoma involving the bone marrow, bronchial lymph nodes, nasal cavity, lung, heart, stomach, pancreas, pancreatic lymph nodes, liver, spleen, and kidney. To the best of our knowledge, this is the first report of disseminated histiocytic sarcoma in chinchillas.

Objective The purpose of this study is to find the clinical and radiographic characteristics of traumatic craniocervical junction (CCJ) injuries requiring occipitocervical fusion (OC fusion) for early diagnosis and surgical intervention. Methods We retrospectively reviewed 12 patients with CCJ injuries presenting to St. Michaels Hospital in Toronto who underwent OC fusion and looked into the following variables; (1) initial trauma data on emergency room arrival, (2) associated injuries, (3) imaging characteristics of computed tomography (CT) scan and magnetic resonance imaging (MRI), (4) surgical procedures, surgical complications, and neurological outcome. Results All patients were treated as acute spinal injuries and underwent OC fusion on an emergency basis. Patients consisted of 10 males and 2 females with an average age of 47 years (range, 18–82 years). All patients sustained high-energy injuries. Three patients out of 6 patients with normal BAI (basion-axial interval) and BDI (basion-dens interval) values showed visible CCJ injuries on CT scans. However, the remaining 3 patients had no clear evidence of occipitoatlantal instability on CT scans. MRI clearly described several findings indicating occipitoatlantal instability. The 8 patients with normal values of ADI (atlantodens interval interval) demonstrated atlantoaxial instability on CT scan, however, all MRI more clearly and reliably demonstrated C1/2 facet injury and/or cruciate ligament injury. Conclusion We advocate measures to help recognize CCJ injury at an early stage in the present study. Occipitoatlantal instability needs to be carefully investigated on MRI in addition to CT scan with special attention to facet joint and ligament integrity.

Abstract A recurrent ZSWIM6 variant, NM_020928.2:c.2737C>T [p.Arg913*], was identified in a Japanese male patient with severe neurodevelopmental delay, epilepsy, distinctive facial features, microcephaly, growth deficiency, abnormal behavior, and frequent vomiting but without frontonasal or limb malformations. In this patient, distinctive facial features gradually became apparent with age, and severe vomiting caused by gastroesophageal reflux continued even after percutaneous endoscopic gastrostomy.

ObjectiveTo assess exposure levels to electromagnetic fields (EMFs) among library workers in Japan, focusing on co-exposure to intermediate-frequency EMF (IF-EMF) and pulsed EMF, to propose a new epidemiological research methodology.MethodsThe evaluated exposure sources were an electromagnetic type-electronic article surveillance gate (EM-EAS, IF-EMF (operating frequency 220 Hz-14 kHz)) and an activator/deactivator of anti-theft tags termed as “book check unit” (BCU, pulsed EMF). Short-term exposures were: (E1) whole-body exposure from the EAS gate when sitting within 3 m; (E2) local exposure to transient IF-EMF while passing through or beside the EAS gate; and (E3) local exposure to a pulsed magnetic field on BCU use. E1–E3 were evaluated based on exposure levels relative to magnetic flux density at the occupational reference level (RL; E1) or as per occupational basic restrictions (BR; E2 and E3) delineated by the International Commission on Non-Ionizing Radiation Protection (ICNIRP) 2010 guidelines. Exposure indices based on mid-term exposure (D1–D3), assuming exposure according to employment on a weekly basis, were used to assess exposure in actual working conditions. D1 represents continuous exposure from an EAS gate when sitting within 3 m of the gate. D2 and D3 represent repeated transient exposures occurring during gate pass or on the operation of a BCU. A link to a web-based questionnaire was distributed to librarians working at all libraries where the authors had mailed institutional questionnaires (4,073 libraries). Four exposure patterns were defined according to various exposure scenarios.ResultsWe obtained information on exposure parameters and working conditions from the 548 completed questionnaires. The ICNIRP guideline levels were not exceeded in any of the E1–E3 scenarios. Median of the D1 (% ICNIRP RL × hour/week) was 1, and >85% respondents had values 10 times the median. The median of D3 (% ICNIRP BR × BCU operation) was 10, and most respondents' D3 values were greater than their D2 values, although the derived results depended on the assumptions made for the estimation.ConclusionWe conducted an assessment of combined exposures to IF-EMF and pulsed EMF among library workers in Japan by evaluating both short-term exposures (E1–E3) and exposure indices based on mid-term exposures (D1–D3) assuming actual working conditions per questionnaire results. These results provide useful information for future epidemiological studies.

Lissencephaly is a severe brain malformation associated with abnormal formation of cerebral sulci. Until now, many genes related to lissencephaly have been identified. Among them, classical lissencephaly has been often related to the platelet activating factor acetylhydrolase 1B regulatory subunit 1 gene (PAFAH1B1). We identified a novel PAFAH1B1 splicing variant (NM_000430.3:c.118-2A>G) in a female patient with classical lissencephaly manifesting as developmental delay, growth failure, and epilepsy. This variant was not detected in her parents, indicating de novo occurrence of the variant in the patient. To confirm whether this variant is in fact related to splicing error, RNA expression was analyzed. As suspected, an abnormal short band excluding exon 4 was additionally detected. This evidence confirmed that the novel variant is definitely pathogenic to cause lissencephaly in the patient.

Exposure to magnetic fields from the electronic article surveillance (EAS) gate was evaluated in consideration of the application to epidemiological studies of library workers who are exposed continually to intermediate frequency magnetic fields from the EAS gate. Two types of exposures were investigated. One was transient exposure due to passing through or beside the gate and another was chronic exposure in the room. We measured magnetic fields from five EAS gate models which were commonly used in libraries in Japan. Detailed measurements were performed for two of them in consideration of the phase difference of vector components of magnetic flux density. The polarization of the magnetic field in the gate was investigated with the index of ellipticity. The induced electric field in a human body was numerically calculated for exposures to magnetic fields of the two gate models. The results provide a quantitative understanding of exposures during passing through or by the EAS gate. Magnetic field distribution was measured in a large room for one gate model to quantify the chronic exposure of library workers during the work at the desk. It was found that the magnetic field was distributed as a function of the horizontal distance to the nearest gatepost. The 45-point average value BIEC defined by the IEC standard was suggested to be a useful quantity to characterize the magnitude of the magnetic field from the EAS gate. Exposures to different EAS gates are expected to be compared through this quantity without detailed measurements. These results are expected to provide useful means for exposure assessment of epidemiological studies on the association between the IF-EMF exposure and possible health outcomes.

This study aimed to identify salivary metabolomic biomarkers for predicting the prognosis of oral squamous cell carcinoma (OSCC) based on comprehensive metabolomic analyses. Quantified metabolomics data of unstimulated saliva samples collected from patients with OSCC (n = 72) were randomly divided into the training (n = 35) and validation groups (n = 37). The training data were used to develop a Cox proportional hazards regression model for identifying significant metabolites as prognostic factors for overall survival (OS) and disease-free survival. Moreover, the validation group was used to develop another Cox proportional hazards regression model using the previously identified metabolites. There were no significant between-group differences in the participants’ characteristics, including age, sex, and the median follow-up periods (55 months [range: 3–100] vs. 43 months [range: 0–97]). The concentrations of 5-hydroxylysine (p = 0.009) and 3-methylhistidine (p = 0.012) were identified as significant prognostic factors for OS in the training group. Among them, the concentration of 3-methylhistidine was a significant prognostic factor for OS in the validation group (p = 0.048). Our findings revealed that salivary 3-methylhistidine is a prognostic factor for OS in patients with OSCC.

Origami structures with curved creases (curved origami structures) have gained extensive attention in several fields. It is well-known that self-locking is one of characteristics of the curved origami structure. When the self-locking occurs, its shape is fixed without external forces. On the view of computer-aided design for the curved origami structure, many studies have focused on computational modeling methods of its shape. However, there are few methods to evaluate mechanical characteristics of the curved origami structures and to simulating folding behavior from unfolded state to folded state with occurring self-locking. Therefore, this study proposes a new computational modeling method for the curved origami structure. In the proposed method, truss elements are applied to creases modeling in finite element analysis and the self-locking is simulated using stepwise forced displacements. To clarify availability of the proposed method, design and simulation problems of origami grippers which are curved origami structures with occurring self-locking are investigated. Through this investigation, feasibility of origami grippers is also discussed.

Genetic analysis in glioma has been developed recently. Spinal cord glioma is less common than intracranial glioma. Thus, the clinical significance of genetic mutations in spinal cord gliomas remains unclear. Furthermore, because the spinal cord is an important communication channel between the brain and the rest of the body, increased attention should be paid to its functional prognosis. In this study, we investigated the functional prognosis and driver genetic mutations in eight patients with spinal cord gliomas (World Health Organization grade I, three cases; grade II, two cases; grade III/IV, three cases). IDH mutations were detected in all grade II cases and H3F3A mutations were detected in all grade III/IV cases. The functional status of grade I and II gliomas remained unchanged or improved 1 year after surgery, whereas grade III/IV gliomas remained unchanged or deteriorated. Spinal glioma progenitor cells with H3F3A mutations were associated with accelerated tumor-associated spinal cord injury, which led to functional impairment. Conversely, the presence of IDH mutations, which are rarely reported in spinal gliomas, indicated a relatively favorable functional prognosis.

Abstract Backgrounds The main culprit lesion causing hiccup in patients with ischemic stroke is thought to involve the medulla oblongata, but some cases of hiccups caused by damage to the supratentorial cortex have been reported. The present study aimed to address the clinical and radiological characteristics of acute stroke patients accompanied by hiccups caused by supratentorial lesions. Method We retrospectively studied 5,309 consecutive patients with acute ischemic stroke or transient ischemic attack who were admitted to our institute within 7 days after onset between April 2006 and September 2017. We searched for the term “hiccup” in prospectively collected descriptive datasets and analyzed associations between hiccup and clinical and radiological findings, with particular focus on patients with supratentorial lesions. Results We finally selected 16 stroke patients accompanied by hiccup. Nine patients had infarcts in the lateral medulla oblongata, and others had supratentorial infarcts (three patients with cortical infarcts, four patients with subcortical infarcts). Moreover, the right hemisphere was frequently damaged in this series (6/7, 86%). Conclusions Hiccup could be caused by supratentorial infarcts including the insular cortex, temporal lobe, and subcortex.

Both adrenal catecholamines and steroids are known to be involved in the stress response, immune function, blood pressure and energy homeostasis. The response to stress is characterized by the activation of the hypothalamus–pituitary–adrenal (HPA) axis and the sympathetic-adrenomedullary system, though the correlation with activation and development is not well understood. We evaluated the stress response of both cortisol and catecholamines during development in zebrafish. Zebrafish at two different stages of development were stressed in one of two different ways and cortisol and catecholamine were measured. Cortisol was measured by enzyme immune assay and catecholamine was measured by ELISA. Our results show that stress responses are delayed until after the synthesis of both cortisol and catecholamines. These observations suggest that the development of HPA axis may be required for the acquisition of the stress response for cortisol and catecholamines.

Polyamines (PAs) are small aliphatic polycations that are found ubiquitously in all organisms. In plants, PAs are involved in diverse biological processes such as growth, development, and stress responses. In Arabidopsis thaliana, the arginine decarboxylase enzymes (ADC1 and 2) catalyze the first step of PA biosynthesis. For a better understanding of PA biological functions, mutants in PA biosynthesis have been generated; however, the double adc1/adc2 mutant is not viable in A. thaliana. In this study, we generated non-lethal A. thaliana lines through an artificial microRNA that simultaneously silenced the two ADC genes (amiR:ADC). The generated transgenic lines (amiR:ADC-L1 and -L2) showed reduced AtADC1 and AtADC2 transcript levels. For further analyses the amiR:ADC-L2 line was selected. We found that the amiR:ADC-L2 line showed a significant decrease of their PA levels. The co-silencing revealed a stunted growth in A. thaliana seedlings, plantlets and delay in its flowering rate; these phenotypes were reverted with PA treatment. In addition, amiR:ADC-L2 plants displayed two seed phenotypes, such as yellow and brownish seeds. The yellow mutant seeds were smaller than adc1, adc2 mutants and wild type seeds; however, the brownish were the smallest seeds with arrested embryos at the torpedo stage. These data reinforce the importance of PA homeostasis in the plant development processes.

The present study investigated whether word width and length affect the optimal character size for reading of horizontally scrolling Japanese words, using reading speed as a measure. In Experiment 1, three Japanese words, each consisting of 4 Hiragana characters, sequentially scrolled on a display screen from right to left. Participants, all Japanese native speakers, were instructed to read the words aloud as accurately as possible, irrespective of their order within the sequence. To quantitatively measure their reading performance, we used rapid serial visual presentation paradigm, where the scrolling rate was increased until the participants began to make mistakes. Thus, the highest scrolling rate at which the participants’ performance exceeded 88.9% correct rate was calculated for each character size (0.3, 0.6, 1.0, and 3.0°) and scroll window size (5 or 10 character spaces). Results showed that the reading performance was highest in the range of 0.6° to 1.0°, irrespective of the scroll window size. Experiment 2 investigated whether the optimal character size observed in Experiment 1 was applicable for any word width and word length (i.e., the number of characters in a word). Results showed that reading speeds were slower for longer than shorter words and the word width of 3.6° was optimal among the word lengths tested (3, 4, and 6 character words). Considering that character size varied depending on word width and word length in the present study, this means that the optimal character size can be changed by word width and word length.

Functional mobility and cognitive function often decline with age. We previously found that functional mobility as measured by the Timed Up and Go Test (TUG) was associated with cognitive performance for visually-encoded (i.e. for location and face) working memory (WM) in older adults. This suggests a common neural basis between TUG and visual WM. To elucidate this relationship further, the present study aimed to examine the neural basis for the WM-mobility association. In accordance with the well-known neural compensation model in aging, we hypothesized that attentional brain activation for easy WM would increase in participants with lower mobility. The data from 32 healthy older adults were analyzed, including brain activation during easy WM tasks via functional Magnetic Resonance Imaging and mobility performance via both TUG and a simple walking test. WM performance was significantly correlated with TUG but not with simple walking. Some prefrontal brain activations during WM were negatively correlated with TUG performance, while positive correlations were found in subcortical structures including the thalamus, putamen and cerebellum. Moreover, activation of the subcortical regions was significantly correlated with WM performance, with less activation for lower WM performers. These results indicate that older adults with lower mobility used more cortical (frontal) and fewer subcortical resources for easy WM tasks. To date, the frontal compensation has been proposed separately in the motor and cognitive domains, which have been assumed to compensate for dysfunction of the other brain areas; however, such dysfunction was less clear in previous studies.The present study observed such dysfunction as degraded activation associated with lower performance, which was found in the subcortical regions. We conclude that a common dysfunction -compensation activation pattern is likely the neural basis for the association between visual WM and functional mobility.

Recent studies have found that self-motion perception induced by simultaneous presentation of visual and auditory motion is facilitated when the directions of visual and auditory motion stimuli are identical. They did not, however, examine possible contributions of auditory motion information for determining direction of self-motion perception. To examine this, a visual stimulus projected on a hemisphere screen and an auditory stimulus presented through headphones were presented separately or simultaneously, depending on experimental conditions. The participant continuously indicated the direction and strength of self-motion during the 130-s experimental trial. When the visual stimulus with a horizontal shearing rotation and the auditory stimulus with a horizontal one-directional rotation were presented simultaneously, the duration and strength of self-motion perceived in the opposite direction of the auditory rotation stimulus were significantly longer and stronger than those perceived in the same direction of the auditory rotation stimulus. However, the auditory stimulus alone could not sufficiently induce self-motion perception, and if it did, its direction was not consistent within each experimental trial. We concluded that auditory motion information can determine perceived direction of self-motion during simultaneous presentation of visual and auditory motion information, at least when visual stimuli moved in opposing directions (around the yaw-axis). We speculate that the contribution of auditory information depends on the plausibility and information balance of visual and auditory information.

Bacteria are essential components of all natural and many engineered systems. The most active fractions of bacteria are now recognized to occur as ‘biofilms’, where cells are attached and surrounded by a secreted matrix of sticky extracellular polymeric substances (EPS). Recent investigations have established that significant accumulation of nanoparticles (NPs) occurs in aquatic biofilms. These studies point to the emerging roles of biofilms for influencing partitioning and possibly transformations of NPs in both natural and engineered systems. While attached biofilms are efficient sponges for NPs, efforts to elucidate the fundamental mechanisms guiding interactions between NPs and biofilms have just begun. In this mini review, special attention is focused on NP-biofilm interactions within the aquatic environment. We highlight key physical, chemical and biological processes that affect interactions and accumulation of NPs by bacterial biofilms. We posit that these biofilm processes present the likely possibility for unique biological and chemical transformations of NPs. Ultimately, the environmental fate of NPs is influenced by biofilms, and therefore requires a more-in depth understanding of their fundamental properties.

The Polycomb Repressive Complex 2 (PRC2) is an evolutionarily conserved multimeric protein complex in both plants and animals. In contrast to animals, plants have evolved a range of different components of PRC2 and form diverse complexes that act in the control of key regulatory genes at many stages of development during the life cycle. A number of studies, particularly in the model species Arabidopsis thaliana, have highlighted the role of PRC2 and of epigenetic controls via parent-of-origin specific gene expression for endosperm development. However, recent research in cereal plants has revealed that although some components of PRC2 show evolutionary conservation with respect to parent-of-origin specific gene expression patterns, the identity of the imprinted genes encoding PRC2 components is not conserved. This disparity may reflect the facts that cereal plant genomes have undergone different patterns of duplication during evolution compared to Arabidopsis thaliana and that the endosperm development program is not identical in monocots and eudicots. In this context, we focus this review on the expression of imprinted PRC2 genes and their roles in endosperm development in cereals.

Recent fMRI studies have shown that functional networks can be extracted even from resting state data, the so called resting state networks (RSNs) by applying independent component analysis (ICA). However, compared to fMRI, EEG and MEG have much higher temporal resolution and provide a direct estimation of cortical activity. To date, MEG studies have applied ICA for separate frequency bands only, disregarding cross-frequency couplings. In this study, we aimed to detect EEG-RSNs and their interactions in all frequency bands. We applied low resolution brain electromagnetic tomography-ICA (LORETA-ICA) to resting-state EEG data in 80 healthy subjects using five frequency bands (delta, theta, alpha, beta and gamma band) and found five RSNs in alpha, beta and gamma frequency bands. Next, taking into account these frequency properties, five RSNs were identified; 1) the visual network, 2) dual-process of visual perception network, characterized by a negative correlation between the right ventral visual pathway (VVP) and left posterior dorsal visual pathway (DVP), 3) self-referential processing network, characterized by a positive correlation between the medial PFC and right VVP, 4) dual-process of memory perception network, functionally related to a negative correlation between the left VVP and the precuneus and 5) sensorimotor network. To detect aging-related changes of these five RSNs, the subjects were divided into three age groups: younger, middle aged, and elderly group, and Student's t test with Bonferroni correction on each coefficient of five independent components were performed. We found a significant attenuation in dual-process of visual perception network in elderly relative to middle aged subjects. Overall findings indicate that LORETA-ICA with EEG data can precisely identify five RSNs in their intrinsic frequency bands, and correct correlations and aging-related changes between and within RSNs.

The inner ear was previously assumed to be an immune-privileged organ due to the existence of its tight junction-based blood-labyrinth barrier. However, studies performed during the past decade revealed that the mesenchymal region of the cochlea, including its lateral wall, is a common site of inflammation. Neutrophils do not enter this region, which is consistent with the old dogma; however, bone marrow-derived resident macrophages are always present in the spiral ligament of the lateral wall and are activated in response to various types of insults, including noise exposure, ischemia, mitochondrial damage and surgical stress. Recent studies have also revealed another type of immune cell, called perivascular melanocyte-like macrophages (PVM/Ms), in the stria vascularis. These dedicated antigen-presenting cells also control vascular contraction and permeability. This review discusses a series of reports regarding inflammatory/immune cells in the cochlear lateral wall, the pathways involved in cochlear damage and their potential as therapeutic targets.

Various aspects of linguistic experience influence the way we segment, represent, and process speech signals. The Japanese phonetic and orthographic systems represent geminate consonants (double consonants, e.g. /ss/, /kk/) in a unique way compared to other languages: one abstract representation is used to characterize the first part of geminate consonants despite the acoustic difference between two distinct realizations of geminate consonants (silence in the case of e.g. stop consonants and elongation in the case of fricative consonants). The current study tests this discrepancy between abstract representations and acoustic realizations influences how native speakers of Japanese perceive geminate consonants. The experiments used pseudo words containing either the geminate consonant /ss/ or a manipulated version in which the first part was replaced by silence /_s/. The sound /_s/ is acoustically similar to /ss/, yet does not occur in everyday speech. Japanese listeners demonstrated a bias to group these two types into the same category while Italian and Dutch listeners distinguished them. The results thus confirmed that distinguishing fricative geminate consonants with silence from those with sustained frication is not crucial for Japanese native listening. Based on this observation, we propose that native speakers of Japanese tend to segment geminated consonants into two parts and that the first portion of fricative geminates is perceptually similar to a silent duration. This representation is compatible with both Japanese orthography and phonology. Unlike previous studies that were inconclusive in how native speakers segment geminate consonants, our study demonstrated relatively strong effect of Japanese specific listening. Thus the current experimental methods may open up new lines of investigation into the relationship between development of phonological representation, orthography and speech perception.

An emerging field of research focused on fluctuations in brain signals has provided evidence that the complexity of those signals, as measured by entropy, conveys important information about network dynamics (e.g., local and distributed processing). While much research has focused on how neural complexity differs in populations with different age groups or clinical disorders, substantially less research has focused on the basic understanding of neural complexity in populations with young and healthy brain states. The present study used resting-state fMRI data from the Human Connectome Project (Van Essen et al., 2013) to test the extent that neural complexity in the BOLD signal, as measured by multiscale entropy 1) would differ from random noise, 2) would differ between four major resting-state networks previously associated with higher-order cognition, and 3) would be associated with the strength and extent of functional connectivity—a complementary method of estimating information processing. We found that complexity in the BOLD signal exhibited different patterns of complexity from white, pink, and red noise and that neural complexity was differentially expressed between resting-state networks, including the default mode, cingulo-opercular, left and right frontoparietal networks. Lastly, neural complexity across all networks was negatively associated with functional connectivity at fine scales, but was positively associated with functional connectivity at coarse scales. The present study is the first to characterize neural complexity in BOLD signals at a high temporal resolution and across different networks and might help clarify the inconsistencies between neural complexity and functional connectivity, thus informing the mechanisms underlying neural complexity.

Two experiments compared young and older adults in order to examine whether aging leads to a larger dependence on visual articulatory movements in auditory-visual speech perception. These experiments examined accuracy and response time in syllable identification for auditory-visual (AV) congruent and incongruent stimuli. There were also auditory-only (AO) and visual-only (VO) presentation modes. Data were analyzed only for participants with normal hearing. It was found that the older adults were more strongly influenced by visual speech than the younger ones for acoustically identical signal-to-noise ratios (SNRs) of auditory speech (Experiment 1). This was also confirmed when the SNRs of auditory speech were calibrated for the equivalent AO accuracy between the two age groups (Experiment 2). There were no aging-related differences in VO lipreading accuracy. Combined with response time data, this enhanced visual influence for the older adults was likely to be associated with an aging-related delay in auditory processing.

The carotenoids produced by extremely halophilic archaeon Haloarcula japonica were extracted and identified by their chemical, chromatographic, and spectroscopic characteristics (UV-Vis and mass spectrometry). The composition (mol%) was 68.1% bacterioruberin, 22.5% monoanhydrobacterioruberin, 9.3% bisanhydrobacterioruberin, < 0.1% isopentenyldehydrorhodopin, and trace amounts of lycopene and phytoene. The in vitro scavenging capacity of a carotenoid, bacterioruberin, extracted from Ha. japonica cells against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals was evaluated. The antioxidant capacity of bacterioruberin was much higher than that of β-carotene.

The total number of new attendant patients diagnosed as having atopic dermatitis at our dermatology outpatient clinic during the 7 year period from 1989 to 1995 was 10 156. Patients from each year during this period were divided into eight age groups. The birth month and the month of first visit for each age group was obtained in average of 7 years. Only for subjects aged

We tried to evaluate the role of IgG antibodies in the wheal and flare reaction of infantile atopic dermatitis by in vivo skin-sensitizing methods. Sera from 49 patients under 6 years of age were heated at 56 °C for 30 min to inactivate IgE antibodies, according to previous reports. Two-fold serial dilutions of the heated serum were injected intracutaneously in both forearms of a non-allergic recipient. One hour later, the whole egg antigen (1:1000) was injected in the serum transfer sites of an arm and the reaction was read at 15 min (IgG Prausnitz-Küstner (P-K) test). Immediately afterwards, a raw hen's egg was swallowed by the recipient and the serum transfer sites of the other arm were observed for 2 h (oral IgG P-K test). Three patients under 1 year of age showed an immediate wheal and flare reaction in the IgG P-K test, but none of the patients showed a positive reaction in the oral IgG P-K test. The patients with a positive IgG P-K test had an IgE radioallergosorbent test (RAST) score >4 to egg white and a positive IgE P-K titer of >28 to whole egg antigen. Two patients showed a positive reaction to the oral IgE P-K test to raw egg ingestion. Ovalbumin-specific IgG, lgG3 and lgG4 antibodies were assayed in 20 patients. IgG, and lgG3 antibodies were significantly increased in two patients with a positive IgG P-K test, while levels of the lgG4 antibody in positive patients were not significantly increased in comparison with levels in negative patients. In conclusion, these results suggest that the IgG antibody may play a role in the immediate type allergic reaction in infantile atopic dermatitis.

Populations of neurons in the hypothalamic preoptic area (POA) fire rapidly during sleep, exhibiting sleep/waking state-dependent firing patterns that are the reciprocal of those observed in the arousal system. The majority of these preoptic sleep-active neurons contain the inhibitory neurotransmitter GABA. On the other hand, a population of neurons in the lateral hypothalamic area (LHA) contains orexins, which play an important role in the maintenance of wakefulness, and exhibit an excitatory influence on arousal-related neurons. It is important to know the anatomical and functional interactions between the POA sleep-active neurons and orexin neurons, both of which play important, but opposite roles in regulation of sleep/wakefulness states. In this study, we confirmed that specific pharmacogenetic stimulation of GABAergic neurons in the POA leads to an increase in the amount of NREM sleep. We next examined direct connectivity between POA GABAergic neurons and orexin neurons using channelrhodopsin 2 (ChR2) as an anterograde tracer as well as an optogenetic tool. We expressed ChR2-eYFP selectively in GABAergic neurons in the POA by AAV-mediated gene transfer, and examined the projection sites of ChR2-eYFP-expressing axons, and the effect of optogenetic stimulation of ChR2-eYFP on the activity of orexin neurons. We found that these neurons send widespread projections to wakefulness-related areas in the hypothalamus and brain stem, including the LHA where these fibers make close appositions to orexin neurons. Optogenetic stimulation of these fibers resulted in inhibition of orexin neurons. These observations suggest direct connectivity between POA GABAergic neurons and orexin neurons.

Recently, by using a combination of two viral vectors, we developed a technique for pathway-selective and reversible synaptic transmission blockade, and successfully induced a behavioral deficit of dexterous hand movements in macaque monkeys by affecting a population of spinal interneurons. To explore the capacity of this technique to work in other pathways and species, and to obtain fundamental methodological information, we tried to block the crossed tecto-reticular pathway, which is known to control orienting responses to visual targets, in mice. A neuron-specific retrograde gene transfer vector with the gene encoding enhanced tetanus neurotoxin (eTeNT) tagged with enhanced green fluorescent protein (EGFP) under the control of a tetracycline responsive element was injected into the left medial pontine reticular formation. 7–17 days later, an adeno-associated viral vector with a highly efficient Tet-ON sequence, rtTAV16, was injected into the right superior colliculus. 5–9 weeks later, the daily administration of doxycycline (Dox) was initiated. Visual orienting responses toward the left side were impaired 1 - 4 days after Dox administration. Anti-GFP immunohistochemistry revealed that a number of neurons in the intermediate and deep layers of the right superior colliculus were positively stained, indicating eTeNT expression. After the termination of Dox administration, the anti-GFP staining returned to the baseline level within 28 days. A second round of Dox administration, starting from 28 days after the termination of the first Dox administration, resulted in the reappearance of the behavioral impairment. These findings showed that pathway-selective and reversible blockade of synaptic transmission causes behavioral effects also in rodents, and that the crossed tecto-reticular pathway surely controls visual orienting behaviors.

The ability to update associative memory is an important aspect of episodic memory and a critical skill for social adaptation. Previous research with younger adults suggests that emotional arousal alters brain mechanisms underlying memory updating; however, it is unclear whether this applies to older adults. Given that the ability to update associative information declines with age, it is important to understand how emotion modulates the brain processes underlying memory updating in older adults. The current study investigated this question using reversal learning tasks, where younger and older participants (age ranges 19-35 and 61-78 respectively) learn a stimulus–outcome association and then update their response when contingencies change. We found that younger and older adults showed similar patterns of activation in the frontopolar OFC and the amygdala during emotional reversal learning. In contrast, when reversal learning did not involve emotion, older adults showed greater parietal cortex activity than did younger adults. Thus, younger and older adults show more similarities in brain activity during memory updating involving emotional stimuli than during memory updating not involving emotional stimuli.

Measles virus (MV) is an enveloped negative strand RNA virus belonging to the family of Paramyxoviridae, genus Morbillivirus, and causes one of the most contagious diseases in humans. Experimentally infected non-human primates are used as animal models for studies of the pathogenesis of human measles. We established a reverse genetics system based on a highly pathogenic wild-type MV (IC-B strain). Infection of monkeys with recombinant MV strains generated by reverse genetics enabled analysis of the molecular basis of MV pathogenesis. In addition, recombinant wild-type MV strains expressing enhanced green fluorescent protein enable visual tracking of MV-infected cells in vitro and in vivo. To date, 3 different molecules have been identified as receptors for MV. Signaling lymphocyte activation molecule (SLAM, also called CD150), expressed on immune cells, is a major receptor for MV. CD46, ubiquitously expressed in all nucleated cells in humans and monkeys, is a receptor for vaccine and laboratory strains of MV. The newly identified nectin-4 (also called PVRL4) is an epithelial cell receptor for MV. The impact of MV receptor usage in vivo on disease outcomes is now under investigation.

PIWI-interacting RNAs (piRNAs) are germline-specific small non-coding RNAs that form piRNA-induced silencing complexes (piRISCs) by associating with PIWI proteins, a subclade of the Argonaute proteins predominantly expressed in the germline. piRISCs protect the integrity of the germline genome from invasive transposable DNA elements by silencing them. Multiple piRNA biogenesis factors have been identified in Drosophila. The majority of piRNA factors are localized in the nuage, electron-dense non-membranous cytoplasmic structures located in the perinuclear regions of germ cells. Thus, piRNA biogenesis is thought to occur in the nuage in germ cells. Immunofluorescence analyses of ovaries from piRNA factor mutants have revealed a localization hierarchy of piRNA factors in female nuage. However, whether this hierarchy is female-specific or can also be applied in male gonads remains undetermined. Here, we show by immunostaining of both ovaries and testes from piRNA factor mutants that the molecular hierarchy of piRNA factors shows gender-specificity, especially for Krimper (Krimp), a Tudor-domain containing protein of unknown function(s): Krimp is dispensable for PIWI protein Aubergine (Aub) nuage localization in ovaries but Krimp and Aub require each other for their proper nuage localization in testes. This suggests that the functional requirement of Krimp in piRNA biogenesis may be different in male and female gonads.

Background: Melanoma metastases to the CNS rank third in frequency, just after lung and breast metastases. There is controversy regarding the factors predisposing to developing CNS metastases in patients with cutaneous melanoma and their survival with conventional treatments., Methods: We carried out a retrospective analysis in a third-level hospital in Mexico to determine epidemiological aspects of melanoma metastases to the central nervous system, factors related to its appearance, clinical presentation, and survival in three treatment groups: surgery, radiotherapy, and conservative management., Results: We found that the nodular variant has the most significant association with CNS metastases. In addition, the superficial spreading variant has the highest risk of presenting a more substantial number of lesions, up to seven for each case and predominantly in the infratentorial space. On the other hand, we found more remarkable survival in patients treated only with surgery than those treated with radiotherapy or conservatively., Conclusions: This study lays the foundations for future prospective survival analysis of the different current treatment modalities for metastatic melanoma in the brain and spine. It also highlights the clinical risk factors for metastatic brain and spine tumors of melanoma., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)