Publications by authors named "Hiroki Nakata"

153 Publications

Comparative anatomy on the development of sperm transporting pathway between the testis and mesonephros.

Histochem Cell Biol 2022 Jan 6. Epub 2022 Jan 6.

Department of Anatomy, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku, Tokyo, 160-8402, Japan.

The male genital tract is diverse among vertebrates, but its development remains unclear, especially in the rete region. In this study, we investigated the testis-mesonephros complex of rabbit, chicken, and frog (Xenopus tropicalis) by immunohistochemistry for markers such as Ad4BP/Sf-1 (gonadal somatic and rete cells in mammals) and Pax2 (mesonephric tubules), and performed a three-dimensional reconstruction. In all investigated animals, testis cords were bundled at the mesonephros side. Rete cells positive for Ad4BP/Sf-1 (rabbit) or Pax2 (chicken and frog) were clustered at the border region between the testis and mesonephros. The cluster possessed two types of cords; one connected to the testis cords and the other to the mesonephric tubules. The latter rete cords were contiguous to Bowman's capsules in rabbit and chicken but to nephrostomes in frog. In conclusion, this study showed that mammals, avian species, and frogs commonly develop the bundle between the testis cords (testis canal) and the cluster of rete cells (lateral kidney canal), indicating that these animals share basic morphogenesis in the male genital tract. The connection site between the rete cells and mesonephric tubules is suggested to have changed from the nephrostome to the Bowman's capsule during vertebrate evolution from anamniote to amniote.
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http://dx.doi.org/10.1007/s00418-021-02057-xDOI Listing
January 2022

Three-dimensional morphological analysis of spermatogenesis in aged mouse testes.

Sci Rep 2021 11 26;11(1):23007. Epub 2021 Nov 26.

Department of Integrative Cancer Therapy and Urology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.

Spermatogenesis, which is a continuous process from undifferentiated spermatogonia to spermatozoa in the seminiferous tubules, declines with age. To investigate changes in spermatogenesis with aging, we reconstructed the seminiferous tubules of 12 mice aged 12 to 30 months from serial sections and examined age-related and region-specific alterations in the seminiferous epithelium and spermatogenic waves in three dimensions. The basic structure of the seminiferous tubules, including the numbers of tubules, terminating points, branching points, and total tubule length, did not change with age. Age-related alterations in spermatogenesis, primarily assessed by the formation of vacuoles in Sertoli cells, were detected in the seminiferous tubules at 12 months. The proportion of altered tubule segments with impaired spermatogenesis further increased by 24 months, but remained unchanged thereafter. Altered tubule segments were preferentially distributed in tubule areas close to the rete testis and those in the center of the testis. Spermatogenic waves became shorter in length with age. These results provide a basis for examining the decline of spermatogenesis not only with aging, but also in male infertility.
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http://dx.doi.org/10.1038/s41598-021-02443-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626501PMC
November 2021

Modality differences in ERP components between somatosensory and auditory Go/No-go paradigms in prepubescent children.

PLoS One 2021 8;16(11):e0259653. Epub 2021 Nov 8.

Department of Health Sciences, Faculty of Human Life and Environment, Nara Women's University, Nara, Japan.

We investigated modality differences in the N2 and P3 components of event-related potentials (ERPs) between somatosensory and auditory Go/No-go paradigms in eighteen healthy prepubescent children (mean age: 125.9±4.2 months). We also evaluated the relationship between behavioral responses (reaction time, reaction time variability, and omission and commission error rates) and amplitudes and latencies of N2 and P3 during somatosensory and auditory Go/No-go paradigms. The peak latency of No-go-N2 was significantly shorter than that of Go-N2 during somatosensory paradigms, but not during auditory paradigms. The peak amplitude of P3 was significantly larger during somatosensory than auditory paradigms, and the peak latency of P3 was significantly shorter during somatosensory than auditory paradigms. Correlations between behavioral responses and the P3 component were not found during somatosensory paradigms. On the other hand, in auditory paradigms, correlations were detected between the reaction time and peak amplitude of No-go-P3, and between the reaction time variability and peak latency of No-go-P3. A correlation was noted between commission error and the peak latency of No-go-N2 during somatosensory paradigms. Compared with previous adult studies using both somatosensory and auditory Go/No-go paradigms, the relationships between behavioral responses and ERP components would be weak in prepubescent children. Our data provide findings to advance understanding of the neural development of motor execution and inhibition processing, that is dependent on or independent of the stimulus modality.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0259653PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575285PMC
December 2021

Three-dimensional reconstruction of testis cords/seminiferous tubules.

Reprod Med Biol 2021 Oct 14;20(4):402-409. Epub 2021 Sep 14.

Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa Japan.

Background: Due to the development of novel equipment for the acquisition of two-dimensional serial images and software capable of displaying three-dimensional (3D) images from serial images, the accurate 3D reconstruction of organs and tissues has become possible.

Methods: Based on published studies, this review summarizes techniques for the 3D reconstruction of the testis cords/seminiferous tubules, with special reference to our method using serial paraffin sections and 3D visualization software.

Main Findings: The testes of mice, rats, and hamsters of various ages were 3D reconstructed and species and age differences in the structures of the testis cords/seminiferous tubules were analyzed. Our method is advantageous because conventional paraffin-embedded normal and pathological specimens may be utilized for the 3D analysis without the need for complicated and expensive equipment.

Conclusion: By further decreasing the time and labor required for the procedure and adding information on molecular localization, the technique for 3D reconstruction will contribute to the elucidation of not only the structures, but also the functions of various organs, including the testis.
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http://dx.doi.org/10.1002/rmb2.12413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499590PMC
October 2021

Human papillomavirus detected in sperm of Japanese infertile males affects reproductive parameters.

Int J Infect Dis 2021 Nov 20;112:294-299. Epub 2021 Sep 20.

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

Objectives: The effects of human papillomavirus (HPV) infection on male reproductive parameters are currently a matter of controversy. In order to clarify the issue in Japanese infertile men, the prevalence and localization of HPV in semen, sperm parameters, and superoxide dismutase (SOD) activity in seminal plasma were examined in 216 Japanese infertile men.

Methods: DNA was extracted from liquid-based cytological semen samples. The β-globin gene was amplified by polymerase chain reaction (PCR), and HPV-DNA was amplified using nested PCR with MY09/MY11 as outer primers and GP5+/GP6+ as inner primers. HPV genotyping was performed in the HPV-positive samples. In addition, SOD levels in seminal plasma were analysed quantitatively. In-situ hybridization (ISH) was performed to localize HPV-DNA in sperm from HPV-positive samples.

Results: Any-risk and high-risk prevalence rates of HPV in semen were 12.5% and 6.9%, respectively. No significant difference in the prevalence of HPV was observed between azoospermic and non-azoospermic subjects. Among non-azoospermic patients, those with HPV detected in semen had significantly lower sperm motility and concentration compared with subjects without HPV detected in semen. SOD levels in seminal plasma were significantly higher in HPV-positive patients compared with HPV-negative patients. ISH analysis of HPV-positive samples revealed that HPV-DNA was localized to the head and mid-piece of sperm. HPV-DNA was present in the sperm of young infertile men.

Conclusion: HPV infection of sperm was associated with reduced sperm motility and concentration, and resulted in an increase in seminal SOD activity.
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http://dx.doi.org/10.1016/j.ijid.2021.09.029DOI Listing
November 2021

Three-dimensional analysis of mesonephric tubules remodeling into efferent tubules in the male mouse embryo.

Dev Dyn 2021 Aug 10. Epub 2021 Aug 10.

Department of Anatomy, Tokyo Medical University, Tokyo, Japan.

Background: Spermatozoa are transported to the epididymal duct through efferent tubules. Although the origin of the efferent tubules is thought to be mesonephric tubules (MTs), their detailed developmental process, for example, where the rete testis and efferent tubules are connected, is unclear. We investigated the structural changes of the MTs in the male mouse embryo using a three-dimensional reconstruction method.

Results: Three to six MTs were connected to the Wolffian duct, and some of them branched, resulting in five to nine tips. Rete cells contacted the three to six tips. The MTs showed a folded shape when the gonadal fate was determined. After the testis development started, they became short and straight but emerged as long and twisting by birth. Before birth, the efferent duct was composed of MTs and a cranial portion of the folded Wolffian duct.

Conclusions: The contact between the rete testis and efferent tubules is possibly established at the tip of each MT. The MTs regress after gonadal fate is determined but is remodeled to the twisting efferent tubules by birth. The efferent tubules are composed of the MTs but also a cranial portion of the folded Wolffian duct in the mouse.
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http://dx.doi.org/10.1002/dvdy.410DOI Listing
August 2021

Effects of passive heat stress and recovery on human cognitive function: An ERP study.

PLoS One 2021 20;16(7):e0254769. Epub 2021 Jul 20.

Department of Health Sciences Health Sciences, Faculty of Human Life and Environment, Nara Women's University, Nara City, Japan.

Using event-related potentials (ERPs), we investigated the effects of passive heat stress and recovery on the human cognitive function with Flanker tasks, involving congruent and incongruent stimuli. We hypothesized that modulation of the peak amplitude and latency of the P300 component in ERP waveforms would differ with task difficulty during passive heat stress and recovery. Subjects performed the Flanker tasks before (Pre), at the end of whole body heating (Heat: internal temperature increase of ~1.2°C from the pre-heat baseline), and after the internal temperature had returned to the pre-heat baseline (Recovery). The internal temperature was regulated by a tube-lined suit by perfusing 50°C water for heat stress and 25°C water for recovery immediately after the heat stress. Regardless of task difficulty, the reaction time (RT) was shortened during Heat rather than Pre and Recovery, and standard deviations of RT (i.e., response variability) were significantly smaller during Heat than Pre. However, the peak amplitudes of the P300 component in ERPs, which involved selective attention, expectancy, and memory updating, were significantly smaller during Heat than during Pre, suggesting the impairment of neural activity in cognitive function. Notably, the peak amplitudes of the P300 component were higher during Recovery than during Heat, indicating that the impaired neural activity had recovered after sufficient whole-body cooling. An indicator of the stimulus classification/evaluation time (peak latency of P300) and the RT were shortened during Heat stress, but such shortening was not noted after whole-body cooling. These results suggest that hyperthermia affects the human cognitive function, reflected by the peak amplitude and latency of the P300 component in ERPs during the Flanker tasks, but sufficient treatment such as whole-body cooling performed in this study can recover those functions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254769PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291678PMC
November 2021

Three-dimensional structure of testis cords in mice and rats.

Andrology 2021 11 21;9(6):1911-1922. Epub 2021 Jun 21.

Department of Integrative Cancer Therapy and Urology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.

Background: Testis cord elongation and coiling, which occur in the final stage of testis formation, have been attributed to Sertoli cell proliferation; however, the underlying mechanisms remain unclear.

Objective: The aim of the present study was to clarify the precise three-dimensional structure of testis cords in the final stage of testis formation in mice and rats.

Materials And Methods: We reconstructed whole testis cords in the final stage of testis formation in mice (on embryonic days 15.5 and 18.5) and rats (on embryonic days 16.5 and 19.5) using serial paraffin sections and high-performance three-dimensional reconstruction software.

Results: Detailed morphometric parameters were calculated for three-dimensionally reconstructed testis cords in six mouse and rat testes each. The mean numbers of testis cords in mice and rats were 12.7 and 27.8, respectively. The mean number of branching points per testis cord was 1.52 in mice, whereas it was only 0.30 in rats. In contrast, the mean ratio of the inner cords, that is, cords not in contact with the tunica albuginea, was 23.0% in rats, whereas it was only 6.5% in mice. In both species, the cords on the cranial side coiled more strongly than those on the caudal side, consistent with the greater expansion of the testis volume on the caudal side. All cords formed right-handed helices from the rete testis side.

Discussion And Conclusions: The present results suggest that testis cords undergo anastomosis at a higher frequency in mice than in rats and that the coiling of testis cords proceeds from the cranial to caudal side of the testis in both species.
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http://dx.doi.org/10.1111/andr.13069DOI Listing
November 2021

A new flavonoid derivative exerts antitumor effects against androgen-sensitive to cabazitaxel-resistant prostate cancer cells.

Prostate 2021 04 25;81(5):295-306. Epub 2021 Jan 25.

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.

Background: Our previous report has shown that the flavonoid 2'-hydroxyflavanone (2'-HF) showed inhibition of androgen receptor (AR) activity against androgen-sensitive prostate cancer (PCa) cells, LNCaP, and exhibited antitumor effects against androgen-insensitive PCa cells, PC-3, and DU145. In the present study, we prepared a derivative of 2'-HF, 16MS7F1924, and confirmed the effects of this derivative on PCa cells.

Methods: The antiproliferation effects of 16MS7F1924 were investigated in PCa cells using LNCaP, PC-3, DU145 and docetaxel-resistant and cabazitaxel-resistant cell lines of PC-3-TxR/CxR and DU145-TxR/CxR. Prostate-specific antigen (PSA) and AR expression level in whole cells and the nucleus were confirmed in LNCaP by reverse transcriptase polymerase chain reaction and Western blot analysis. AR activity in LNCaP cells was confirmed by luciferase assay using PSA promoter-driven reporter. To analyze the antiproliferative effects, cell-based assays using flow cytometry, immunocytochemistry, and TUNEL assay as well as Western blot analysis were employed. Furthermore, PC-3, DU145 and each chemoresistant strain of human PCa cells were subcutaneously xenografted. The antitumor effects of 16MS7F1924 were evaluated in vivo.

Results: 16MS7F1924 showed antitumor effect on all PCa cells in a dose-dependent manner. 16MS7F1924 reduced the expression of PSA messenger RNA (mRNA) and protein and inhibited AR activity in a dose-dependent manner, while expression of AR protein and mRNA was reduced by 16MS7F1924. 16MS7F1924 induced mitotic catastrophe and apoptosis. Apoptotic cells were increased in a dose-dependent manner, and the apoptosis was mediated through the Akt pathway. Tumor growth was safely and significantly inhibited by both intraperitoneal and oral administration of 16MS7F1924 in vivo.

Conclusion: 16MS7F1924 had sufficient antitumor activity against androgen-sensitive and cabazitaxel-resistant PCa cells and may be useful as a novel therapeutic agent overcoming hormone- and chemoresistant PCas.
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http://dx.doi.org/10.1002/pros.24106DOI Listing
April 2021

Anti-proliferative and anti-migratory properties of coffee diterpenes kahweol acetate and cafestol in human renal cancer cells.

Sci Rep 2021 01 12;11(1):675. Epub 2021 Jan 12.

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8640, Japan.

Despite improvements in systemic therapy options for renal cancer, it remains one of the most drug-resistant malignancies. Interestingly, reports have shown that kahweol and cafestol, natural diterpenes extracted from coffee beans, exhibit anti-cancer activity. However, the multiple potential pharmacological actions of both have yet to be fully understood. This study therefore investigated the effects of kahweol acetate and cafestol on human renal cancer ACHN and Caki-1 cells. Accordingly, the combination of kahweol acetate and cafestol administration synergistically inhibited cell proliferation and migration by inducing apoptosis and inhibiting epithelial-mesenchymal transition. Mechanistic dissection revealed that kahweol acetate and cafestol inhibited Akt and ERK phosphorylation. Moreover, kahweol acetate and cafestol downregulated the expression of not only C-C chemokine receptors 2, 5, and 6 but also programmed death-ligand 1, indicating their effects on the tumor microenvironment. Thus, kahweol acetate and cafestol may be novel therapeutic candidates for renal cancer considering that they exert multiple pharmacological effects.
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http://dx.doi.org/10.1038/s41598-020-80302-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804192PMC
January 2021

Three-Dimensional Analysis of Busulfan-Induced Spermatogenesis Disorder in Mice.

Front Cell Dev Biol 2020 17;8:609278. Epub 2020 Dec 17.

Department of Integrative Cancer Therapy and Urology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.

We examined if the distribution of impaired or normal spermatogenesis differs along the length of seminiferous tubules in disorders of spermatogenesis. For this purpose, three-dimensional (3D) reconstruction of seminiferous tubules was performed in mice with experimental spermatogenesis disorder induced by intraperitoneal injection of busulfan, and the areas of impaired and normal spermatogenesis were analyzed microscopically. The volume of the testis and length of seminiferous tubules decreased, and the proportion of tubule areas with impaired spermatogenesis increased depending on the dose of busulfan. With the highest dose of busulfan, although the proportion of impaired spermatogenesis was similar among individual seminiferous tubules, it was slightly but significantly higher in shorter tubules and in tubule areas near branching points. The tubule areas with impaired and normal spermatogenesis consisted of many segments of varying lengths. With increasing doses of busulfan, the markedly impaired segments increased in length without changing in number, whereas normal segments, although reduced in number and length, remained even with the highest dose of busulfan. Individual remaining normal segments consisted of several different stages, among which stage I and XII were found at higher frequencies, and stage VI at a lower frequency than expected in normal seminiferous tubules. We also examined if the distribution of impaired or normal spermatogenesis differs among different 3D positions in the testis without considering the course of seminiferous tubules. Although the proportions of impaired spermatogenesis with the minimum dose of busulfan and normal spermatogenesis with the highest dose of busulfan greatly varied by location within a single testis, there were no 3D positions with these specific proportions common to different testes, suggesting that the factors influencing the severity of busulfan-induced spermatogenesis disorder are not fixed in location among individual mice.
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http://dx.doi.org/10.3389/fcell.2020.609278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773783PMC
December 2020

Three-dimensional structure of seminiferous tubules in the Syrian hamster.

J Anat 2021 01 24;238(1):86-95. Epub 2020 Jul 24.

Department of Integrative Cancer Therapy and Urology, School of Medical Sciences, Kanazawa University, Kanazawa, Japan.

The hamster is useful for the study of male reproductive biology. However, unlike in the mouse and rat, the gross structure of seminiferous tubules in the hamster is largely unknown. The aim of the present study was to clarify the precise 3-dimensional (3D) structure of seminiferous tubules in hamsters. We reconstructed all seminiferous tubules in 3 and 1 testes from 0-day (P0) and 10-week (adult) Syrian hamsters, respectively, using serial paraffin sections and high-performance 3D reconstruction software. In P0 hamsters, the average numbers of seminiferous tubules, terminating points, branching points, and blind ends per testis were 9.0, 89.7, 93.0, and 0.7, respectively. There were two types of tubules: shorter and dominant ones. The dominant tubules, 2-4 in number per testis and accounting for 86% of the total tubule length, had many terminating and branching points and appeared to be derived from the anastomosis of many shorter tubules. In an adult hamster, there were 11 seminiferous tubules with a total length of 22 m, 98 terminating points, 88 branching points, and 2 blind ends per testis. Three of the 11 tubules were dominant ones, accounting for 83% of the total length, and occupied the testis from the surface over the circumference to the center, while the others were short and occupied only one side of the testis. The amplitude and direction of the curves of tubules were random, and there were no funnel-shaped networks of tubules present, in contrast to the mouse testis. The present study revealed the 3D structure of seminiferous tubules in developing and adult Syrian hamsters, which is different from that in mice and rats.
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http://dx.doi.org/10.1111/joa.13287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754951PMC
January 2021

Relative Age Effects in Male Japanese Professional Athletes: a 25-Year Historical Analysis.

Sports Med Open 2020 Oct 6;6(1):48. Epub 2020 Oct 6.

Faculty of Human Life and Environment, Nara Women's University, Kitauoya-Nishimachi, Nara, 630-8506, Japan.

Background: The mechanisms underlying the relative age effect (RAE), a biased distribution of birth dates, in sport events have been investigated for more than two decades. The present study comprised an historical analysis involving the most recent quarter-century (1993-2018) on RAEs among Japanese male professional athletes (soccer, baseball, basketball, and volleyball) to clarify how the RAEs changed over time.

Methods: Birth data were obtained from 7805 Japanese male professional athletes registered in 1993, 2001, 2010, and 2018. The athletes were divided into four groups based on their month of birth: quartiles Q1 (April-June), Q2 (July-September), Q3 (October-December), and Q4 (January-March of the following year). In addition, based on the data in 1993 for soccer and baseball and in 2010 for basketball and volleyball, the expected numbers of players were calculated in 2001, 2010, and 2018 for soccer and baseball, and 2018 for basketball and volleyball.

Results: Significant RAEs were observed among soccer and baseball players in 1993, 2001, 2010, and 2018, and strong tendencies of RAEs were found among basketball and volleyball players in 2010 and 2018. The magnitudes of the RAEs in soccer, baseball, and volleyball decreased over time, but not in basketball.

Conclusion: The exact reasons for the decreasing or unchanging RAEs among these professional players remain unclear, but socio-cultural factors, such as low birthrates and the popularity of sports in Japan, might be related to the changing RAEs.
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http://dx.doi.org/10.1186/s40798-020-00277-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538493PMC
October 2020

The relationship between cognitive style and sensory gating during auditory and somatosensory tasks.

Neurosci Lett 2020 11 6;738:135354. Epub 2020 Sep 6.

Department of Health Sciences, Faculty of Human Life and Environment, Nara Women's University, Nara, Japan. Electronic address:

Cognitive styles such as field dependence/independence and empathizing influence individual personalities. Sensory gating is conceptualized as an automatic inhibitory function related to human higher cognitive processing. The present study investigated the relationship between cognitive styles and the automatic inhibitory function using electroencephalographic evoked potentials (EPs) during auditory and somatosensory tasks with a paired stimulus. The Embedded-Figures Test (EFT) and Empathy Questionnaire (EQ) were performed to assess the cognitive styles (field dependence: FD; field independence: FI; empathizing: EM; non-empathizing: Non-EM). Sensory gating was evaluated as an amplitude ratio of EP responses to the second stimulus (S2) over responses to the first stimulus (S1). Subjects were divided into two groups based on EFT scores (FD vs. FI) or EQ scores (EM vs. Non-EM). The S2/S1 amplitude ratio of the auditory long-latency component was significantly smaller in the FD than FI group, while the S2/S1 amplitude ratio of a somatosensory long-latency component was significantly smaller in the FI than FD group. In contrast, these differences in the S2/S1 amplitude ratios of any auditory and somatosensory components were not observed between EM and Non-EM groups. Our results suggest that sensory gating conceptualized as an automatic inhibitory function is related to FD and FI cognitive styles.
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http://dx.doi.org/10.1016/j.neulet.2020.135354DOI Listing
November 2020

The lack of terminal tubule cells in the submandibular gland of mice deficient in submandibular gland protein C.

Cell Tissue Res 2020 Aug 16;381(2):229-237. Epub 2020 May 16.

Department of Clinical Engineering, Faculty of Health Sciences, Komatsu University, Komatsu, Japan.

The submandibular gland (SMG) of newborn mice has no mature acini but has the rudiments of acini called terminal tubules (TT). The TT are composed of TT cells with dark secretory granules and proacinar cells with lighter secretory granules, the latter being considered the immediate precursor of mature acinar cells. TT cells contain a specific secretory protein, submandibular gland protein C (SMGC) and they decrease in number postnatally at a higher rate in males than in females. In the present study, in order to clarify the biological roles of TT cells and their secretory product SMGC, we generated a knockout (KO) mouse strain deficient in SMGC. The KO mice of both sexes grew normally, had normal reproductive capacity and had normal acinar and duct systems in the SMG in adult ages. However, through the neonatal and early postnatal stages, the KO mice were deficient not only in the production of SMGC but also in TT cells. With electron microscopy of the SMG of newborn KO mice, TT cells with characteristic granules were absent and replaced by undifferentiated ductal cells, whereas proacinar cells were normal. These results suggested that the absence of SMGC inhibits the development of TT cells and that the absence of SMGC and TT cells has no notable influence on the postnatal development of the acinar and duct systems in the SMG.
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http://dx.doi.org/10.1007/s00441-020-03205-wDOI Listing
August 2020

Reply to Comment on "Kadomoto, S. et al. Tumor-Associated Macrophages Induce Migration of Renal Cell Carcinoma Cells via Activation of the CCL20-CCR6 Axis" Cancers 2020 12, 89.

Cancers (Basel) 2020 Feb 4;12(2). Epub 2020 Feb 4.

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8641, Japan.

We appreciate Zins and Abraham [1] commenting on our paper studying the role of the CCL20-CCR6 axis on renal cell carcinoma (RCC) cells [2]. As they pointed out, our study has certain limitations. Although M1- and M2-types cannot be separated clearly and a consecutive change of character might exist between them, it has been reported that plural specific markers express on M1- and M2-types. Unfortunately, a definite difference between M1 and M2 macrophages was not confirmed in our study. For more differentiation, multiple stimulations, such as suggested in the comments of Zins and Abraham, might be needed. Hence, we needed to expediently use "M1-like" and "M2-like" to mention specific status of these macrophage-like cells. Meanwhile, CCL20 expression levels of M2-like-THP-1 cells co-cultured with RCC cells were dramatically increased compared with parental THP-1 cells, indicating that certain stimulations within the tumor microenvironment rather than theoretical stimulations make macrophages differentiated; however, further studies are needed to clarify this mechanism using a more appropriate co-culture system mimicking the tumor microenvironment. Immunohistochemistry of CCL20 and M2 markers will help to better understand the role of tissue infiltrating macrophages, even tissue CD68 staining intensity itself was reported to correlate with prognosis of RCC patients [3]. [...].
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http://dx.doi.org/10.3390/cancers12020354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073159PMC
February 2020

Tumor-Associated Macrophages Induce Migration of Renal Cell Carcinoma Cells via Activation of the CCL20-CCR6 Axis.

Cancers (Basel) 2019 Dec 30;12(1). Epub 2019 Dec 30.

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8641, Japan.

This study investigated tumor-associated macrophages activity in the microenvironment of renal cell carcinoma. Via a co-culture with macrophage-like cells differentiated from human monocyte cell line THP-1 and U937 cells, the migration ability of ACHN and Caki-1 cells, which are human renal cell carcinoma cell line cells, was significantly increased, as was the epithelial-mesenchymal transition change. A chemokine array identified the CCL20-CCR6 axis as a concentration-dependent signal in ACHN and Caki-1 cell migration. Akt in the ACHN and Caki-1 cells was activated by macrophage-like cells, and the CCL20 neutralizing antibody suppressed migration ability, epithelial-mesenchymal transition, and Akt phosphorylation in the ACHN and Caki-1 cells. Akt inhibitor AZD5363 also decreased the epithelial-mesenchymal transition change and migration ability in the ACHN and Caki-1 cells. In 42 renal cell carcinoma tissues, patients with CCR6 and macrophage infiltration indicated poor prognoses. In the tumor microenvironment of renal cell carcinoma, cancer cells are activated by CCL20 secreted by tumor-associated macrophages through Akt activation, followed by epithelial-mesenchymal transition and an acquired migration ability. Thus, inhibition of the CCL20-CCR6 axis may be a potential therapeutic strategy for renal cell carcinoma.
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http://dx.doi.org/10.3390/cancers12010089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017081PMC
December 2019

Differences in characteristics of somatosensory evoked potentials between children and adults.

Neuroreport 2019 12;30(18):1284-1288

Department of Health Sciences, Faculty of Human Life and Environment, Nara Women's University, Nara, Japan.

The present study examined the characteristics of somatosensory processing in healthy prepubescent children (mean age: 124.9 ± 3.8 months) compared with young adults. Somatosensory evoked potentials at the frontal (Fz) and centroparietal (C3') electrodes were recorded by delivering an electrical stimulus to the right median nerve at a rate of 3 Hz. The characteristics of somatosensory evoked potential waveforms at C3' were markedly different between the two groups, while those at Fz were similar. Specifically, the waveforms at C3' in the children involved not only standard P12, N18, P22, N27, P45, and N60 components, but also additional positive (P3) and negative (N3) components between N27 and P45, which were not found in adults. The amplitude of P22 at C3' was significantly larger in the children than adults, indicating hyper-excitability/responsiveness of neural activity on somatosensory processing. In contrast, the amplitudes of N15 at Fz and N27 at C3' were smaller in the children than adults, suggesting an immature somatosensory system in the children. The peak latencies of P12, N15, and P18 at Fz, and P12 and N18 at C3' were significantly shorter in the children than adults, which was dependent on the height. These results indicate the developing somatosensory processing with hyper- and hypo-excitability of neural activity in prepubescent children.
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http://dx.doi.org/10.1097/WNR.0000000000001355DOI Listing
December 2019

Birch-Type Reduction of Arenes in 2-Propanol Catalyzed by Zero-Valent Iron and Platinum on Carbon.

ACS Omega 2019 Jul 2;4(7):11522-11531. Epub 2019 Jul 2.

Laboratory of Organic Chemistry, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu 501-1196, Japan.

Catalytic arene reduction was effectively realized by heating in 2-propanol/water in the presence of Pt on carbon (Pt/C) and metallic Fe. 2-Propanol acted as a hydrogen source, obviating the need for flammable (and hence, dangerous and hard-to-handle) hydrogen gas, while metallic Fe acted as an essential co-catalyst to promote reduction. The chemical states of Pt and Fe in the reaction mixture were determined by X-ray absorption near-edge structure analysis, and the obtained results were used to suggest a plausible reaction mechanism, implying that catalytic reduction involved Pt- and Fe-mediated single-electron transfer and the dehydrogenation of 2-propanol.
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http://dx.doi.org/10.1021/acsomega.9b01130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682079PMC
July 2019

The difference in hemodynamic responses between dominant and non-dominant hands during muscle contraction and relaxation: An fNIRS study.

PLoS One 2019 19;14(7):e0220100. Epub 2019 Jul 19.

Faculty of Human Life and Environment, Nara Women's University, Nara City, Japan.

The present study used functional near-infrared spectroscopy (fNIRS), and investigated the differences in neural activation of ipsi- or contralateral hemispheres between right dominant and left non-dominant hands among right-handed subjects using consecutive motor tasks with muscle contraction and relaxation. The subjects performed tasks under four conditions: (1) right hand up (R-Up), (2) left hand up (L-Up), (3) right hand down (R-Down), and (4) left hand down (L-Down). The peak amplitude of oxy-Hb was significantly larger at the contralateral than ipsilateral hemisphere in the premotor area (PM) under the R-Up condition, and no significant differences were observed between contra- and ipsilateral hemispheres under the L-Up condition. In addition, the peak amplitude was more negative at the contra- than ipsilateral hemisphere in the PM under the R-Down condition, while the peak amplitude was significantly more negative at the ipsi- than contralateral hemisphere in the PM under the L-Down condition. These results suggest that the PM of the left hemisphere among right-handed subjects plays an important role in muscle contraction and relaxation with force control.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220100PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6641204PMC
March 2020

Effects of whole body skin cooling on human cognitive processing: a study using SEPs and ERPs.

Am J Physiol Regul Integr Comp Physiol 2019 09 10;317(3):R432-R441. Epub 2019 Jul 10.

Department of Health Sciences, Faculty of Human Life and Environment, Nara Women's University, Nara, Japan.

The present study investigated the effect of whole body skin cooling on somatosensory ascending processing by utilizing somatosensory-evoked potentials (SEPs) and motor execution, as well as inhibitory processing by event-related potentials (ERPs). Fourteen healthy participants wearing a water-perfused suit performed two sessions ( and ) consisting of SEPs and ERPs with somatosensory Go/No-go paradigms under two conditions (cold stress and control) on different days. In , under the cold stress condition, whole body skin cooling was achieved by circulating 20°C water through the suit for 40 min, whereas 34°C water was perfused in the other sessions. The mean skin temperature decreased from 35.0 ± 0.5°C () to 30.4 ± 0.9°C () during whole body skin cooling, but the internal temperature was maintained. Whole body skin cooling delayed the peak latencies of N20, P25, and P45 components at C4' of SEPs (all: < 0.05). Moreover, the peak latencies of P14, N18, and P22 components at Fz of SEPs and the Go-P300 component of ERPs were delayed (all: < 0.05). In contrast, the peak amplitudes of all individual components of SEPs as well as N140 and P300 of ERPs remained unchanged. These results suggest that passive whole body skin cooling delays neural activities on somatosensory processing and higher cognitive function.
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http://dx.doi.org/10.1152/ajpregu.00087.2019DOI Listing
September 2019

Three-dimensional structure of efferent and epididymal ducts in mice.

J Anat 2019 08 30;235(2):271-280. Epub 2019 May 30.

Department of Histology and Cell Biology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.

The aim of the present study was to clarify the detailed morphology of efferent and epididymal ducts in adult mice using three-dimensional (3D) analysis. We reconstructed efferent and epididymal ducts in three adult mice using serial paraffin sections and high-performance 3D reconstruction software to draw the core lines of all ducts. By comparing the 3D core lines with the histological features in serial sections, we obtained detailed information on the gross characteristics of the ducts and identified the duct divisions accurately. The intra-testicular rete testis penetrated the tunica albuginea at one place and turned into the extra-testicular rete testis, which branched once or twice to give rise to four efferent ducts within 0.5 mm from the tunica albuginea. As these ducts approached the epididymis, they converged into one again and changed abruptly into the initial segment (IS) of the epididymis. The average length from the tunica albuginea to the IS was 19.7 ± 3.1 mm. In one mouse, we found four additional efferent ducts diverging from the common region with blind ends. The epididymal duct was a single highly convoluted duct with no branch and an average length of 767 ± 26 mm. By dividing the epididymal duct into five regions based on its cytological features and periodic acid-Schiff stainability, we calculated the length and diameter of individual regions accurately. Furthermore, we clearly showed locations of the connective tissue septa that divide the head epididymis into several segments. The epididymal duct followed a complicated, winding path within each segment while drawing a large spiral overall along the circumference of the epididymis. Sometimes the direction of this spiral reversed between adjacent segments. The present study revealed the detailed 3D structures of efferent and epididymal ducts in adult mice.
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http://dx.doi.org/10.1111/joa.13006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637445PMC
August 2019

Remote effects on corticospinal excitability during motor execution and motor imagery.

Neurosci Lett 2019 08 21;707:134284. Epub 2019 May 21.

Faculty of Human Life and Environment, Nara Women's University, Nara City, Japan. Electronic address:

We investigated the remote effect on corticospinal excitability of resting left and right hand muscles during motor execution and motor imagery when performing left or right foot plantar flexion. Fifteen right-handed subjects performed two conditions with three tasks: Condition (Motor Execution (ME) vs. Motor Imagery (MI)): Task (Control, Ipsilateral, and Contralateral). From the left and right first dorsal interosseous, motor evoked potentials (MEPs) elicited by a single-pulse transcranial magnetic stimulation (TMS) to the left or right primary motor cortices (M1) were recorded under all six trials. MEP amplitudes were significantly larger under the ME than MI condition, irrespective of hands and tasks. MEP amplitudes were also the largest during the Contralateral tasks, irrespective of the condition and hands. The correlation analysis showed that MEP amplitudes were significantly correlated between ME and MI conditions with both left and right hands. Our results indicate that the magnitude of the remote effect on corticospinal excitability of hand muscles differs between motor execution and motor imagery, and between ipsi- and contralateral limbs, when performing foot plantar flexion.
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http://dx.doi.org/10.1016/j.neulet.2019.134284DOI Listing
August 2019

Negative BOLD responses during hand and foot movements: An fMRI study.

PLoS One 2019 19;14(4):e0215736. Epub 2019 Apr 19.

Faculty of Sport Sciences, Waseda University, Tokorozawa, Japan.

The present study employed functional magnetic resonance imaging (fMRI) to examine the characteristics of negative blood oxygen level-dependent (Negative BOLD) signals during motor execution. Subjects repeated extension and flexion of one of the following: the right hand, left hand, right ankle, or left ankle. Negative BOLD responses during hand movements were observed in the ipsilateral hemisphere of the hand primary sensorimotor area (SMI), medial frontal gyrus (MeFG), middle frontal gyrus (MFG), and superior frontal gyrus (SFG). Negative BOLD responses during foot movements were also noted in the bilateral hand SMI, MeFG, MFG, SFG, inferior frontal gyrus, middle temporal gyrus, parahippocampal gyrus, anterior cingulate cortex, cingulate gyrus (CG), fusiform gyrus, and precuneus. A conjunction analysis showed that portions of the MeFG and CG involving similar regions to those of the default mode network were commonly deactivated during voluntary movements of the right/left hand or foot. The present results suggest that three mechanisms are involved in the Negative BOLD responses observed during voluntary movements: (1) transcallosal inhibition from the contralateral to ipsilateral hemisphere in the SMI, (2) the deactivated neural network with several brain regions, and (3) the default mode network in the MeFG and CG.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215736PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474656PMC
January 2020

Effects of repetitive exercise and thermal stress on human cognitive processing.

Physiol Rep 2019 02;7(4):e14003

Faculty of Human Life and Environment, Department of Health Sciences, Nara Women's University, Nara, Japan.

Cognitive performances may improve after acute moderate exercise, but not after prolonged and/or heavy exercise. The present study aimed to investigate the effects of environmental temperature during exercise on human cognitive processing. Fifteen healthy males performed four bouts of a 15-min cycling exercise with a 10-min rest between each bout, and event-related potentials (ERPs) were recorded in five sessions during somatosensory Go/No-go paradigms (i.e., Pre, post-first exercise bout, post-second exercise bout, post-third exercise bout, and post-fourth exercise bout) in an environmental chamber with temperature controlled at 20°C (Temperate) and 35°C (Hot). Increases in external canal temperature and heart rate were greater under the 35°C condition than under the 20°C condition. Regardless of thermal conditions, reaction times (RT) and error rates were not affected by the repetition of moderate exercise, whereas the peak amplitude of the N140 component, which is mainly related to somatosensory processing, was significantly reduced with the repetition of the exercise. However the peak amplitude of P300, which is linked to cognitive processes of context updating, context closure, and event-categorization, was significantly smaller in post-third and post-fourth exercise bouts under the 35°C condition than under the 20°C condition, and this decrease was more prominent in No-go trials under the 35°C condition. These results suggest that executive function, which is based on RTs and error rates, is not affected by prolonged exercise and different thermal conditions, whereas the exercise in a hot environment impairs human cognitive processing, particularly response inhibition.
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http://dx.doi.org/10.14814/phy2.14003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383110PMC
February 2019

Chemoselective Nucleophilic Functionalizations of Aromatic Aldehydes and Acetals via Pyridinium Salt Intermediates.

J Org Chem 2019 Apr 20;84(7):3853-3870. Epub 2019 Feb 20.

Laboratory of Organic Chemistry , Gifu Pharmaceutical University , 1-25-4, Daigaku-nishi , Gifu 501-1196 , Japan.

The development of a novel chemoselective functionalization can diversify the strategy for synthesizing the target molecules. The perfect chemoselectivity between aromatic and aliphatic aldehydes is difficult to achieve by the previous methods. The aromatic aldehyde-selective nucleophilic addition in the presence of aliphatic aldehydes was newly accomplished. Namely, the aromatic aldehyde-selective nucleophilic addition using arenes and allyl silanes proceeded in the presence of trialkylsilyl triflate and 2,2'-bipyridyl, while the aliphatic aldehydes completely remained unchanged. The reactive pyridinium-type salt intermediate derived from an aromatic aldehyde chemoselectively underwent the nucleophilic substitution. Moreover, the aromatic acetals as the protected aldehydes could be directly transformed into similar pyridinium salt intermediates, which reacted with various nucleophiles coexisting with the aliphatic aldehydes.
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http://dx.doi.org/10.1021/acs.joc.8b02965DOI Listing
April 2019

Assessment of brain mechanisms involved in the processes of thermal sensation, pleasantness/unpleasantness, and evaluation.

IBRO Rep 2019 Jun 7;6:54-63. Epub 2019 Jan 7.

Body Temperature and Fluid Laboratory, Faculty of Human Sciences, Waseda University, Tokorozawa, Japan.

The conscious perception of thermal stimuli is divided into two categories: thermal sensation (i.e., discriminative component) and pleasantness/unpleasantness (i.e., hedonic component). There have been very few studies which clearly dissociated the two components. The aim of the present study was 1) to identify brain regions involved in perception of thermal stimuli per se, dissociating those related to the two components, and additionally 2) to examine brain regions of the explicit evaluation processes for the two components. Sixteen participants received local thermal stimuli of either 41.5 °C or 18.0 °C during whole-body thermal stimuli of 47.0 °C, 32.0 °C, or 17.0 °C. The local stimuli were delivered to the right forearm with the Peltier device. The whole-body stimuli delivered through a water-perfusion suit was aimed to modulate thermal pleasantness/unpleasantness to the local stimulus. The local stimulation at the same temperature was conducted five times with 30-s intervals. Brain activation was assessed by functional magnetic resonance imaging (fMRI), and the participants were asked to report their ratings of thermal sensation and pleasantness/unpleasantness following the cessation of each local stimulus. Local thermal stimulation activated specific brain regions such as the anterior cingulate cortex, insula, and inferior parietal lobe, irrespective of the temperature of local and whole-body stimuli; however, no specific activation for hot or cold sensation was observed. Different brain regions were associated with pleasantness and unpleasantness; the caudate nucleus and frontal regions for pleasantness, and the medial frontal and anterior cingulate cortex for unpleasantness. In addition, the explicit evaluation process for the discriminative and hedonic components immediately following the cessation of local stimulus involved different brain regions; the medial prefrontal cortex extending to the anterior cingulate cortex, insula, middle frontal cortex, and parietal lobes during the explicit evaluation of thermal sensation, and the medial prefrontal cortex, posterior cingulate cortex, and inferior parietal lobes during that of pleasantness/unpleasantness.
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http://dx.doi.org/10.1016/j.ibror.2019.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329283PMC
June 2019

Comparison of the Position-Matching and Position-Reproducing Tasks to Detect Deficits in Knee Position Sense After Reconstruction of the Anterior Cruciate Ligament.

J Sport Rehabil 2020 Jan;29(1):87-92

Context: Deficits in knee position sense following reconstruction of the anterior cruciate ligament (ACL) can delay an athlete's return to sport participation and increase the risk of reinjury. Deficits in position sense postreconstruction have been evaluated using either a position-reproducing or position-matching task.

Objective: The aim of our study was to combine both to determine which assessment would be more effective to identify deficits in knee position sense.

Design: Longitudinal laboratory-based study.

Participants: Eleven athletes (6 men and 5 women; mean age, 20.5 [1.2] y), who had undergone ACL reconstruction with an ipsilateral hamstring autograft, and 12 age-matched controls.

Interventions: Position sense was evaluated at 6 and 12 months postreconstruction and once for the control group. In addition, peak isokinetic knee extension and flexion strength, at 60°/s and 180°/s, was assessed for the ACL reconstruction group to evaluate possible influences of muscle strength on knee joint position sense.

Main Outcome Measures: The variables include the angular differences between the reference limb and indicator limb, and peak torque values of isokinetic knee extension and flexion.

Results: Significant matching differences were identified at 6 months postsurgery on the position-matching task, but not at 12 months postsurgery. No significant between-group and within-subject differences were identified on the position-reproducing task. No significant matching errors were identified for the control group. There was no correlation between errors in position sense and maximum isokinetic strength.

Conclusion: The position-matching task is more sensitive than the position-reproducing task to identify deficits in knee position sense over the first year following ACL reconstruction surgery.
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http://dx.doi.org/10.1123/jsr.2017-0275DOI Listing
January 2020

Characteristics of Relative Age Effects and Anthropometric Data in Japanese Recreational and Elite Male Junior Baseball Players.

Sports Med Open 2018 Nov 30;4(1):52. Epub 2018 Nov 30.

Faculty of Human Life and Environment, Nara Women's University, Kitauoya-Nishimachi, Nara, 630-8506, Japan.

Background: The mechanisms underlying the relative age effect (RAE), a biased distribution of birth dates, in sport events have been investigated for more than two decades. The present study investigated the characteristics of the RAE in baseball and anthropometric data (height and weight) among recreational junior baseball players as well as elite players, using data extracted from national surveys.

Methods: Birth and anthropometric data were obtained from 4464 Japanese students as elementary school, junior high school, and high school players.

Results: Significant RAEs were noted in recreational junior high school and high school players, but not in elementary school players, and the effect size became larger with increasing grade (0.063 in elementary school players, 0.151 in junior high school players, and 0.227 in high school players). We also observed a significant RAE for elite elementary, junior high, and high school players. However, the effect size of elite players became smaller with increasing grade (0.563 in elementary school players, 0.358 in junior high school players, and 0.343 in high school players). Height and weight values were significantly larger in elite elementary and junior high school players than in recreational elementary and junior high school players, but height was almost the same between recreational and elite high school players.

Conclusion: The characteristics of RAEs differed between recreational and elite junior baseball players. Anthropometric data were also different, depending on birth data, and between recreational and elite baseball players in elementary and junior high school students.
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http://dx.doi.org/10.1186/s40798-018-0165-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265376PMC
November 2018

Effects of stimulus intensity and auditory white noise on human somatosensory cognitive processing: a study using event-related potentials.

Exp Brain Res 2019 Feb 24;237(2):521-530. Epub 2018 Nov 24.

Department of Health Sciences, Faculty of Human Life and Environment, Nara Women's University, Kitauoya-Nishi Machi, Nara, 630-8506, Japan.

Exposure to auditory white noise has been shown to facilitate cognitive function. This phenomenon is often called stochastic resonance, and a moderate amount of auditory noise has been suggested to benefit individuals in hypodopaminergic states. Previous studies using psychophysic methods reported that stochastic resonance was sensitive to stimulus intensity; however, the relationship between neural activities elicited by different stimulus intensities and auditory white noise has not yet been clarified Thus, the present study aimed to investigate the effects of stimulus intensity (Experiment 1) and auditory white noise (Experiment 2) on behavioral data (reaction time (RT), the standard deviation of RT, and error rates), and the N140 and P300 components of event-related potentials (ERPs) in somatosensory Go/No-go paradigms. The subjects had to respond to the somatosensory stimuli by pressing a button with their right thumb only after presentation of the Go stimulus. In Experiment 1 with four different stimulus intensity levels, the peak latencies of N140 and P300 became shorter, and the peak amplitudes of N140 and P300 were enhanced with increases in stimulus intensity. In Experiment 2 with weak and mild intensities under auditory white noise and control conditions, the amplitudes of Go-P300 and No-go-P300 were enhanced by white noise, irrespective of weak and mild intensities, during Go/No-go paradigms. Auditory white noise did not significantly affect the amplitude of N140 or the latencies of N140 and P300. These results suggest the presence of a characteristic cross-modal stochastic resonance in neural substrates utilizing somatosensory ERPs.
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http://dx.doi.org/10.1007/s00221-018-5443-8DOI Listing
February 2019
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