Search

Cosmogenic nuclides in tree rings and polar ice cores record the information of past cosmic ray intensities and solar activities. A large 14C increase over 10 years has been discovered around 5480 BCE. The 14C variations in this event differ from those of other short‐term cosmic ray events and typical grand solar minima. To elucidate the cause of the 14C increase around 5480 BCE, we measured the 10Be and 36Cl concentrations in the Antarctic Dome Fuji ice core at quasi‐annual and 4–5 years resolutions, respectively. Based on the combined 14C, 10Be, and 36Cl data, the 5480 BCE event was probably not caused by a solar proton event (SPE) or a gamma‐ray event, because the 36Cl concentration did not significantly increase as expected in these events. The incremented 10Be data were enhanced similarly to those of recent grand solar minima, but more rapidly increased (over ∼10 years). These results suggest that an unusual grand solar minimum occurred around 5480 BCE, characterized by a rapidly decreasing solar activity. Key Points: New high‐resolution 10Be and 36Cl data for the 5480 BCE cosmic ray event were taken from the Antarctic Dome Fuji ice coreMeasured 36Cl/10Be ratio was not suitable for either solar proton event or gamma‐ray event originsThe 5480 BCE event might refer to the unusual grand solar minimum which solar activity decreased rapidly in ∼10 years [ABSTRACT FROM AUTHOR]

The seizure threshold 2 (SZT2) gene encodes a large, highly conserved protein that is associated with epileptogenesis. In mice, Szt2 is abundantly expressed in the central nervous system. Recently, biallelic SZT2 mutations were found in 7 patients (from 5 families) presenting with epileptic encephalopathy with dysmorphic features and/or non‐syndromic intellectual disabilities. In this study, we identified by whole‐exome sequencing compound heterozygous SZT2 mutations in 3 patients with early‐onset epileptic encephalopathies. Six novel SZT2 mutations were found, including 3 truncating, 1 splice site and 2 missense mutations. The splice‐site mutation resulted in skipping of exon 20 and was associated with a premature stop codon. All individuals presented with seizures, severe developmental delay and intellectual disabilities with high variability. Brain MRIs revealed a characteristic thick and short corpus callosum or a persistent cavum septum pellucidum in each of the 2 cases. Interestingly, in the third case, born to consanguineous parents, had unexpected compound heterozygous missense mutations. She showed microcephaly despite the other case and previous ones presenting with macrocephaly, suggesting that SZT2 mutations might affect head size. [ABSTRACT FROM AUTHOR]

We examined heteroplasmy of mutated mitochondrial DNA in single peripheral lymphocytes derived from 4 individuals carrying the nt 3243 A-to-G mutation, including two patients with MELAS, a patient with cardiomyopathy, deafness and diabetes mellitus, and the asymptomatic mother of one of the MELAS patients. In these subjects, all lymphocytes examined were heteroplasmic to different degrees, with a wider range of heteroplasmy evident in the symptomatic patients than in the healthy carrier. [ABSTRACT FROM AUTHOR]

To clarify the mechanism by which progenitor T (pro-T) cells recognize and enter the thymus, an attempt was made to produce haematopoietic cell lines by the fusion of BALB/c nude mouse bone marrow or foetal liver cells (gestation 14 and 15 days) with AKR thymoma BW5147, thereby immortalizing cells with potency to colonize the thymus, a characteristic of pro-T cells rarely found in adult bone marrow or foetal liver. The hybridomas thus produced were classified according to the phenotype of surface markers, T-cell receptor (TcR) gene configuration and expression. All hybridomas were negative in the surface expression of T-cell markers such as TcR αβ, TcR γδ, CD3, CD4 and CD8. They had TcR β-, γ- and δ-genes, each with a different status with respect to configuration and transcription. Some possessed partially rearranged TcR genes and others expressed immature TcR mRNA. The cell lines were examined for their capacity to colonize the thymus following intravenous injection into recipient mice. It was found that the cells with capacity of colonizing the thymus expressed immature TcR δ mRNA, while the cell lines lacking TcR δ-genes did not home to the thymus. These findings imply that the potency for migrating to thymus is closely associated with the particular stage of prethymic cell differentiation which could be estimated by the analysis of TcR genes, and that some cell lines with the expression of TcR δ-gene mRNA and the ability to colonize the thymus are derived from pro-T cells. [ABSTRACT FROM AUTHOR]

The pathogenesis of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome and the effects of elimination of accessory pathways on the appearance of atrial fibrillation are still controversial. Fifty-four patients with Wolff-Parkinson-White syndrome were classified into three groups: a No AF group (n = 24). patients without paroxysmal atrial fibrillation; an RF-AF Group (n =12), patients with paroxysmal atrial fibrillation whose accessory pathways were eliminated using radiofrequency catheter ablation; and a Cryo-AF Group (n = 18), patients with paroxysmal atrial fibrillation whose accessory pathways were eliminated with surgical cryoablation. The electrophysiological characteristics of each group were evaluated prior to and following the elimination of their accessory pathways. As indices of atrial vulnerability, the presence of fragmented atrial activity and repetitive atrial firing zones were assessed. Inducibility of atrial fibrillation was significantly reduced following ablation of accessory pathways in the Cryo-AF group (83.3%-5.6%, P < 0.0001). while it was unchanged in the RF-AF group (83.3%-75%). In preablation studies, the effective refractory periods of the atrium in the RF-AF group and the Cryo-AF group were significantly shorter compared with the No AF group (204 ± 18 ms, 197 ± 16 ms vs 246 ± 44 ms. respectively. P < 0.0001). Following ablation, the effective refractory period for patients in the Cryo-AF group was significantly prolonged compared with before ablation (197 ± 16 ms to 232 ± 24 ms, P < 0.0001). As a result of this prolongation of the effective refractory period of the atrium, the fragmented atrial activity and repetitive atrial response zones narrowed following ablation in the Cryo-AF group, hut not in the RF-AF group. Therefore, the pathogenesis of atrial fibrillation in patients with Wolff-Parkinson-White syndrome may depend on the refractory period of the atrium rather than on the presence of accessory pathways. [ABSTRACT FROM AUTHOR]

Background: EXCOR Pediatric is one of the most commonly used ventricular assist devices (VAD) for small children; it requires visual inspection of the diaphragm movement to assess its operating status. Although this visual inspection can only be performed by trained medical professionals, it can also be attempted by the recent advances in computer vision technology., Methods: Movement of the diaphragm in the operating EXCOR VAD was recorded as movies and annotated frame-by-frame in three classes according to the state of the diaphragm: "fill," "mid," and "empty." Three models, MobileNetV3, EfficientNetV2, and MobileViT, were trained using the frames, and their performance was evaluated based on the accuracy and area under the receiver operating characteristic curve (AROC)., Results: A total of 152 movies were available from two participants. Only the 10 mL pumps were used. Ninety-eight movies were used for annotation and frame extraction, and 7949 frames per class were included in the analysis. The macro-average accuracies of the three models were 0.88, 0.91, and 0.93, and the AROC were 0.99, 0.98, and 0.99 for MobileNetV3, EfficientNetV2, and MobileViT, respectively., Conclusion: Image recognition models based on lightweight deep neural networks could detect the diaphragm state of EXCOR VAD with sufficient accuracy, although there were limited variations in the dataset. This suggests the potential of computer vision for the automated monitoring of the EXCOR diaphragm position., (© 2024 The Author(s). Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Autism spectrum disorders (ASD) are associated with face perception atypicalities, and atypical experience with faces has been proposed as an underlying explanation. Studying the own-race advantage (ORA) for face recognition can reveal the effect of experience on face perception in ASD, although the small number of studies in the area present mixed findings. This study probed the ORA in ASD by comparing two cultural groups simultaneously for the first time. Children with ASD in the UK (N = 16) and Japan (N = 26) were compared with age- and ability-matched typically developing (TD) children in the UK (N = 16) and Japan (N = 26). Participants completed a two-alternative forced-choice task, whereby they had to recognize a just seen face from a foil which was manipulated in one of four ways (IC: identity change; EE: easy eyes; HE: hard eyes; HM: hard mouth). Face stimuli were Asian and Caucasian, and thus the same stimuli were own and other race depending on the cultural group. The ASD groups in the UK and Japan did not show impaired face recognition abilities, or impairments with recognizing faces depending on manipulations to the eye region, and importantly they showed an ORA. There was considerable heterogeneity in the presence of the ORA in ASD and TD and also across cultures. Children in Japan had higher accuracy than children in the UK, and TD children in Japan did not show an ORA. This cross-cultural study challenges the view that atypical experiences with faces lead to a reduced/absent ORA in ASD., (© 2020 John Wiley & Sons Ltd.)

The thalamic reticular nucleus (TRN) collects inputs from the cerebral cortex and thalamus and, in turn, sends inhibitory outputs to the thalamic relay nuclei. This unique connectivity suggests that the TRN plays a pivotal role in regulating information flow through the thalamus. Here, we analyzed the roles of TRN neurons in visually guided reaching movements. We first used retrograde transneuronal labeling with rabies virus, and showed that the rostro-dorsal sector of the TRN (TRNrd) projected disynaptically to the ventral premotor cortex (PMv). In other experiments, we recorded neurons from the TRNrd or PMv while monkeys performed a visuomotor task. We found that neurons in the TRNrd and PMv showed visual-, set-, and movement-related activity modulation. These results indicate that the TRNrd, as well as the PMv, is involved in the reception of visual signals and in the preparation and execution of reaching movements. The fraction of neurons that were non-selective for the location of visual signals or the direction of reaching movements was greater in the TRNrd than in the PMv. Furthermore, the fraction of neurons whose activity increased from the baseline was greater in the TRNrd than in the PMv. The timing of activity modulation of visual-related and movement-related neurons was similar in TRNrd and PMv neurons. Overall, our data suggest that TRNrd neurons provide motor thalamic nuclei with inhibitory inputs that are predominantly devoid of spatial selectivity, and that these signals modulate how these nuclei engage in both sensory processing and motor output during visually guided reaching behavior., (© 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Coffin-Siris syndrome is a rare congenital malformation and intellectual disability syndrome. Mutations in at least seven genes have been identified. Here, we performed copy number analysis in 37 patients with features of CSS in whom no causative mutations were identified by exome sequencing. We identified a patient with a 9p24.3-p22.2 duplication and another patient with the chromosome der(6)t(6;9)(p25;p21)mat. Both patients share a duplicated 15.8-Mb region containing 46 protein coding genes, including SMARCA2. Dominant negative effects of SMARCA2 mutations may contribute to Nicolaides-Baraitser syndrome. We conclude that their features better resemble Coffin-Siris syndrome, rather than Nicolaides-Baraitser syndrome and that these features likely arise from SMARCA2 over-dosage. Pure 9p duplications (not caused by unbalanced translocations) are rare. Copy number analysis in patients with features that overlap with Coffin-Siris syndrome is recommended to further determine their genetic aspects. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

The dorsal premotor cortex residing in the dorsolateral aspect of area 6 is a rostrocaudally elongated area that is rostral to the primary motor cortex (M1) and caudal to the prefrontal cortex. This region, which is subdivided into rostral [pre-dorsal premotor cortex (pre-PMd)] and caudal [dorsal premotor cortex proper (PMd)] components, probably plays a central role in planning and executing actions to achieve a behavioural goal. In the present study, we investigated the functional specializations of the pre-PMd, PMd, and M1, because the synthesis of the specific functions performed by each area is considered to be essential. Neurons were recorded while monkeys performed a conditional visuo-goal task designed to include separate processes for determining a behavioural goal (reaching towards a right or left potential target) on the basis of visual object instructions, specifying actions (direction of reaching) to be performed on the basis of the goal, and preparing and executing the action. Neurons in the pre-PMd and PMd retrieved and maintained behavioural goals without encoding the visual features of the visual object instructions, and subsequently specified the actions by multiplexing the goals with the locations of the targets. Furthermore, PMd and M1 neurons played a major role in representing the action during movement preparation and execution, whereas the contribution of the pre-PMd progressively decreased as the time of the actual execution of the movement approached. These findings revealed that the multiple processing stages necessary for the realization of an action to accomplish a goal were implemented in an area-specific manner across a functional gradient from the pre-PMd to M1 that included the PMd as an intermediary., (© 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Mutations in the components of the SWItch/sucrose nonfermentable (SWI/SNF)-like chromatin remodeling complex have recently been reported to cause Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NCBRS), and ARID1B-related intellectual disability (ID) syndrome. We detail here the genotype-phenotype correlations for 85 previously published and one additional patient with mutations in the SWI/SNF complex: four with SMARCB1 mutations, seven with SMARCA4 mutations, 37 with SMARCA2 mutations, one with an SMARCE1 mutation, three with ARID1A mutations, and 33 with ARID1B mutations. The mutations were associated with syndromic ID and speech impairment (severe/profound in SMARCB1, SMARCE1, and ARID1A mutations; variable in SMARCA4, SMARCA2, and ARID1B mutations), which was frequently accompanied by agenesis or hypoplasia of the corpus callosum. SMARCB1 mutations caused "classical" CSS with typical facial "coarseness" and significant digital/nail hypoplasia. SMARCA4 mutations caused CSS without typical facial coarseness and with significant digital/nail hypoplasia. SMARCA2 mutations caused NCBRS, typically with short stature, sparse hair, a thin vermillion of the upper lip, an everted lower lip and prominent finger joints. A SMARCE1 mutation caused CSS without typical facial coarseness and with significant digital/nail hypoplasia. ARID1A mutations caused the most severe CSS with severe physical complications. ARID1B mutations caused CSS without typical facial coarseness and with mild digital/nail hypoplasia, or caused syndromic ID. Because of the common underlying mechanism and overlapping clinical features, we propose that these conditions be referred to collectively as "SWI/SNF-related ID syndromes"., (Copyright © 2013 Wiley Periodicals, Inc.)

Osteoporosis-pseudoglioma syndrome (OPS; OMIM 259770) is an autosomal-recessive genetic disorder characterized by severe osteoporosis and visual disturbance from childhood. Biallelic mutations in the low-density lipoprotein receptor-related protein 5 gene (LRP5) have been frequently detected, while a subset of patients had only one or no detectable mutation. We report on the clinical and molecular findings of four unrelated Japanese patients with the syndrome. The four patients had typical skeletal and ocular phenotypes of OPS, namely severe juvenile osteoporosis and early-onset visual disturbance, with or without mental retardation. We undertook standard PCR-based sequencing for LRP5 and found four missense mutations (p.L145F, p.T244M, p.P382L, and p.T552M), one nonsense mutation (p.R1534X), and one splice site mutation (c.1584+1G>A) among four OPS patients. Although three patients had two heterozygous mutations, one had only one heterozygous splice site mutation. In this patient, RT-PCR from lymphocytic RNA demonstrated splice error resulting in 63-bp insertion between exons 7 and 8. Furthermore, the patient was found to have only mutated RT-PCR fragment, implying that a seemingly normal allele did not express LRP5 mRNA. We then conducted custom- designed oligonucleotide tiling microarray analyses targeted to a 600-kb genome region harboring LRP5 and discovered a 7.2-kb microdeletion encompassing exons 22 and 23 of LRP5. We found various types of LRP5 mutations, including an exon-level deletion that is undetectable by standard PCR-based mutation screening. Oligonucleotide tiling microarray seems to be a powerful tool in identifying cryptic structural mutations.

The title complex, [Ir(2)(μ-Cl)(2)(C(8)H(14))(4)], has a dinuclear structure with bridging Cl atoms, a hinge angle of 179.44 (7)° between the two IrCl(2) planes, and an Ir⋯Ir distance of 3.7254 (3) Å. Regarding the coordinating C=C bonds as occupying a single coordination site each, the geometry around each Ir atom is square-planar.

Objectives: To examine the three-dimensional ultrastructure of cricothyroid (CT) muscle fibers to elucidate their morphologic characteristics with regard to the specific functions of the muscle., Study Design: An anatomic animal study., Methods: The CT muscles of five adult rats were processed using the HCl-hydrolysis method to remove the peri- and intramuscular connective tissue components. The fine muscle fiber arrangements were observed by scanning electron microscopy., Results: Complex muscle fiber interconnections (myomyous junctions) were identified in the muscles. Myomyous junctions were characterized by the connection of many villous processes that were 1 to 2 mum in diameter and 2 to 4 mum in length with a serrated appearance at the ends of a lateral branch or a bifurcating trunk of the muscle fibers., Conclusions: Myomyous junctions form a complex muscle fiber network, which is thought to synchronize the activity of the CT muscle fibers. This is the first three-dimensional demonstration of the muscle fiber network in the CT muscle; this network may play a major role in the functional specificity of the CT muscle.

Array using 2,173 BAC clones covering the whole human genome has been constructed. All clones spotted were confirmed to show a unique signal at the predicted chromosomal location by FISH analysis in our laboratory. A total of 30 individuals with idiopathic mental retardation (MR) were analyzed by comparative genomic hybridization using this array. Three deletions, one duplication, and one unbalanced translocation could be detected in five patients, which are likely to contribute to MR. The constructed array was shown to be an efficient tool for the detection of pathogenic genomic rearrangements in MR patients as well as copy number polymorphisms (CPNs)., (2006 Wiley-Liss, Inc.)

Objective: To evaluate the effects of basic fibro-blast growth factor (bFGF) on the recovery of vocal fold movement and the attenuation of laryngeal muscle atrophy after transection of the recurrent laryngeal nerve (RLN)., Study Design: Quantitative assessment of vocal fold movement using the video cassette recorder (VCR) image-analysis method and histologic examination of the laryngeal muscle., Methods: Fifty-eight Wistar rats underwent RLN transection and one of the following three procedures: 1) transection of the RLN alone (transection group, n = 18), 2) suture of the nerve stumps followed by local administration of phosphate-buffered saline (PBS) solution using an osmotic pump (PBS group, n =20), or 3) suture of the nerve stumps followed by local administration of bFGF (FGF group, n = 20). Vocal fold movements were recorded with VCR by way of a rigid endoscope, and the VCR images were analyzed on a computer. Histologic changes in the thyroarytenoid (TA) muscle were evaluated by measuring the cross-sectional area of the muscle and average size of muscle fibers., Results: In the transection group, vocal fold movement did not recover, and atrophy of the TA muscle gradually progressed after sectioning the nerve. In contrast, vocal fold movement as assessed by VCR image-analysis recovered in some cases in the immediate suturing groups, more markedly in the FGF group (34.1 +/- 29.1%) than in the PBS group (5.5 +/- 7.9%) (P <.05). Histologically, atrophy of the laryngeal muscle was significantly attenuated by the local administration of bFGF., Conclusion: bFGF facilitates regeneration of the transected RLN and attenuation of intrinsic laryngeal muscle atrophy, thereby restoring laryngeal function.

A variant form of BCR/ABL junction was identified in a patient with chronic myelogenous leukaemia (CML). The BCR/ABL fusion mRNA of this patient showed in-frame junction between BCR exon c3 and ABL exon 2. Although the diagnosis of CML was made, the patient showed clinical features of essential thrombocythaemia (ET) rather than that of typical CML. Treatment with interferon-alpha showed no cytogenetic response. The c3-a2 type of BCR/ABL junction seems to be associated with elevated platelet count and thus could form a novel clinical entity different from typical CML.

We describe a patient with basophilic leukaemia following a 2-year period with myelodysplastic syndrome (refractory anaemia). The marrow showed 59.4% of blasts with 25.0% of mature and immature basophils. The leukaemic blasts contained granules, positively stained with toluidine blue but negative for peroxidase. The basophilic differentiation was confirmed by ultrastructural analysis demonstrating immature basophil granules. In addition, a morphological transition from immature blasts to more mature basophils was observed. Immunophenotypic analysis of blasts and basophils showed positive for CD5, CD7, CD13, CD33 and CD34. Cytogenetic investigation showed an abnormal karyotype, 46,XY,del(5)(q31q35), in 11% of the cells examined when the initial diagnosis of refractory anaemia was made. However, expansion of the same clone up to 100% was observed concomitantly with transformation to basophilic leukaemia.