Effects of inter-stimulus and inter-trial intervals on somatosensory gating.

AIM OF THE STUDY: Sensory gating is a human higher cognitive function that serves to suppress excessive sensory information and prevent brain overactivity. To elucidate this function, a paired-pulse stimulation paradigm has been used while recording electroencephalography (EEG), and evaluated as an amplitude ratio of responses to a second stimulus (S2) over responses to the first stimulus (S1). The present study investigated the effects of the inter-stimulus interval (ISI) and inter-trial interval (ITI) on somatosensory gating using somatosensory-evoked potentials (SEPs). METHODS: In Experiment 1, ISI was set at five conditions: 200, 400, 600, 800, and 1000 ms. In Experiment 2, ITI was set at four conditions: 1, 2, 4, and 8 s. RESULTS: ISI affected the S2/S1 amplitude ratios of P22 and N27 at C3' and N30 at Fz, and these S2/S1 amplitude ratios decreased the most under the 200 and 400-ms conditions. ITI affected the S2/S1 amplitude ratios of P22, N27, and N60 at C3', and especially, the somatosensory gating did not work under the 1-s condition. These results suggest that not all SEP components are modulated in the same manner with changing ISI and ITI. The effects of ISI and ITI independently affected the somatosensory gating. CONCLUSIONS: Based on our findings, preferable parameters are 200-400 ms for ISI and 4 s or longer for ITI to evaluate the functional mechanisms on somatosensory gating in SEPs.

Oxidative Coupling of Hydroquinone Derivatives with Olefins to Dihydrobenzofurans.

Dihydrobenzofuran is an important skeleton for bioactive compounds and natural products. Hydroquinones can be easily modified into substituted hydroquinones, which effectively undergo oxidation to produce the corresponding benzoquinone derivatives. Benzoquinones are reactive electrophiles that are frequently utilized in coupling with olefins to dihydrobenzofurans. Herein, we report the one-pot oxidative coupling of hydroquinones bearing an electron-withdrawing group at the C2 position with olefins to dihydrobenzofurans in the presence of the Lewis acidic FeCl3 and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) oxidant. Furthermore, this method was applied to the oxidative coupling of N-electron-withdrawing group-substituted 4-aminophenol.

Histopathological growth pattern and vessel co-option in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) exhibits different blood imaging features and prognosis depending on histology. To clarity histopathological growth patterns (HGPs) and vascularization processes of iCCA, we collected 145 surgical specimens and histologically classified them into large bile duct (LBD) (20 cases), small bile duct (SBD) (54), cholangiolocarcinoma (CLC) (35), combined SBD-CLC (cSBD-CLC) (26), and ductal plate malformation (DPM) (10) (sub)types. According to the invasive pattern at the interface between tumor and adjacent background liver, HGPs were classified into desmoplastic, pushing, and replacing HGPs. Desmoplastic HGP predominated in LBD type (55.5%), while replacing HGP was common in CLC (82.9%) and cSBD-CLC (84.6%) subtypes. Desmoplastic HGP reflected angiogenesis, while replacing HGP showed vessel co-option in addition to angiogenesis. By evaluating microvessel density (MVD) using vascular markers, ELTD1 identified vessel co-option and angiogenesis, and ELTD1-positive MVD at invasive margin in replacing HGP was significantly higher than those in desmoplastic and pushing HGPs. REDD1, an angiogenesis-related marker, demonstrated preferably higher MVD in the tumor center than in other areas. iCCA (sub)types and HGPs were closely related to vessel co-option and immune-related factors (lymphatic vessels, lymphocytes, and neutrophils). In conclusion, HGPs and vascular mechanisms characterize iCCA (sub)types and vessel co-option linked to the immune microenvironment.

Sphingosine kinase 1 is involved in triglyceride breakdown by maintaining lysosomal integrity in brown adipocytes.

Sphingosine 1-phosphate (S1P) has been implicated in brown adipose tissue (BAT) formation and energy consumption; however, the mechanistic role of sphingolipids, including S1P, in BAT remains unclear. Here, we showed that, in mice, BAT activation by cold exposure upregulated mRNA and protein expression of the S1P-synthesizing enzyme sphingosine kinase 1 (SphK1) and S1P production in BAT. Treatment of wild-type brown adipocytes with exogenous S1P or S1P receptor subtype-selective agonists stimulated triglyceride (TG) breakdown only marginally, compared with noradrenaline. However, genetic deletion of Sphk1 resulted in hypothermia and diminished body weight loss upon cold exposure, suggesting that SphK1 is involved in thermogenesis through mechanisms different from receptor-mediated, extracellular action of S1P. In BAT of wild-type mice, SphK1 was localized largely in the lysosomes of brown adipocytes. In the brown adipocytes of Sphk1-/- mice, the number of lysosomes was reduced and lysosomal function, including proteolytic activity, acid esterase activity, and motility, was impaired. Concordantly, nuclear translocation of transcription factor EB, a master transcriptional regulator of lysosome biogenesis, was reduced, leading to decreased mRNA expression of the lysosome-related genes in Sphk1-/- BAT. Moreover, BAT of Sphk1-/- mice showed greater TG accumulation with dominant larger lipid droplets in brown adipocytes. Inhibition of lysosomes with chloroquine resulted in a less extent of triglyceride accumulation in Sphk1-/- brown adipocytes compared with wild-type brown adipocytes, suggesting a reduced lysosome-mediated TG breakdown in Sphk1-/- mice. Our results indicate a novel role of SphK1 in lysosomal integrity, which is required for TG breakdown and thermogenesis in BAT.

Suppression of androgen receptor signaling induces prostate cancer migration via activation of the CCL20-CCR6 axis.

The suppression of androgen receptor (AR) expression exacerbates the migration potential of prostate cancer. This study identified a previously unrecognized regulation of the AR-controlled pathway that promotes migration potential in prostate cancer cells. Prostate cancer cells that pass through a transwell membrane (mig cells) have a higher migration potential with a decreased AR expression than parental cells. In this study, we aimed to elucidate the mechanism of migration enhancement associated with the suppression of AR signaling. Expression of C-C motif ligand 20 (CCL20) is upregulated in mig cells, unlike in the parental cells. Knockdown of AR with small interfering RNA (siAR) in LNCaP and C4-2B cells increased CCL20 secretion and enhanced the migration of cancer cells. Mig cells, CCL20-treated cells, and siAR cells promoted cell migration with an enhancement of AKT phosphorylation and Snail expression, while the addition of a C-C chemokine receptor 6 (CCR6, the specific receptor of CCL20) inhibitor, anti-CCL20 antibody, and AKT inhibitor suppressed the activation of AKT and Snail. With 59 samples of prostate cancer tissue, CCL20 secretion was profuse in metastatic cases despite low AR expression levels. Snail expression was associated with the expression of CCL20 and CCR6. A xenograft study showed that the anti-CCL20 antibody significantly inhibited Snail expression, thereby suggesting a new therapeutic approach for castration-resistant prostate cancer with the inhibition of the axis between CCL20 and CCR6.

Expression patterns of sex steroid receptors in developing mesonephros of the male mouse: three-dimensional analysis.

The androgen pathway via androgen receptor (AR) has received the most attention for development of male reproductive tracts. The estrogen pathway through estrogen receptor (ESR1) is also a major contributor to rete testis and efferent duct formation, but the role of progesterone via progesterone receptor (PGR) has largely been overlooked. Expression patterns of these receptors in the mesonephric tubules (MTs) and Wolffian duct (WD), which differentiate into the efferent ductules and epididymis, respectively, remain unclear because of the difficulty in distinguishing each region of the tracts. This study investigated AR, ESR1, and PGR expressions in the murine mesonephros using three-dimensional (3-D) reconstruction. The receptors were localized in serial paraffin sections of the mouse testis and mesonephros by immunohistochemistry on embryonic days (E) 12.5, 15.5, and 18.5. Specific regions of the developing MTs and WD were determined by 3-D reconstruction using Amira software. AR was found first in the specific portion of the MTs near the MT-rete junction at E12.5, and the epithelial expression showed increasing strength from cranial to the caudal regions. Epithelial expression of ESR1 was found in the cranial WD and MTs near the WD first at E15.5. PGR was weakly positive only in the MTs and cranial WD starting on E15.5. This 3-D analysis suggests that gonadal androgen acts first on the MTs near the MT-rete junction but that estrogen is the first to influence MTs near the WD, while potential PGR activity is delayed and limited to the epithelium.

Are bladder washing samples suitable for investigation of HPV infection in urinary bladder? Comparison in HPV prevalence between urine and washing samples.

Although urine and bladder washing samples are commonly used for the cytological evaluation of the bladder mucosa, it has been unknown whether these samples are likely suitable to investigate human papillomavirus (HPV) prevalence in the urinary bladder. The present study aimed to elucidate the appropriateness of spontaneously voided urine or bladder washing in screening HPV infection in the urinary bladder. Urine and bladder washing samples were obtained from 201 patients who underwent transurethral bladder tumor resection. After extracting DNA from both samples, HPV-DNA was examined using a nested polymerase chain reaction with GP5+/6+ and MY09/11 primers. HPV genotyping was performed in the HPV-positive samples. In situ hybridization (ISH) was performed to observe the HPV-DNA localization in urothelial cells among cytological samples and paraffin-embedded tumor tissues in HPV-positive washing samples. HPV prevalence in urine and washing samples were 9.5% and 7.0%, respectively. High-risk HPV prevalence in urine and washing samples was 7.5% and 4.0%, respectively. The most common HPV type was HPV 16, followed by HPV 52 and HPV 18 in both samples. HPV type distribution in both samples was not in agreement (κ = -0.431). The ISH analysis revealed that HPV-DNA signal was observed in urothelial cells of five (55.7%) of nine detectable HPV-positive cytological samples. Six (66.7%) of nine HPV-positive cases had HPV-DNA signals in tumor tissue. The use of washing samples was likely applicable for investigating HPV prevalence in the urinary bladder. HPV-DNA detected in washing samples might be frequently derived from the urinary bladder.

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

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.

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

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.

Three-dimensional analysis and in vivo imaging for sperm release and transport in the murine seminiferous tubule.

Spermatozoa released from Sertoli cells must be transported to the epididymis. However, the mechanism of the luminal flow in seminiferous tubules has remained unclear to date. Therefore, in this study, we investigated luminal flow and movements in the seminiferous tubules by three-dimensional analysis and in vivo imaging. Serial 5-µm-thick mouse testicular sections at 50-µm-intervals were prepared and stained by Periodic Acid-Schiff-hematoxylin. After three-dimensional reconstruction of the seminiferous tubules, the localization of the released spermatozoa and the stages observed in the sections were recorded in each reconstructed tubule. Luminal movements in the seminiferous tubules were observed by in vivo imaging using a fluorescent-reporter mouse and two-photon excitation microscopy system. Spermatozoa without contact to the seminiferous epithelium were not accumulated toward the rete testis. Additionally, such spermatozoa were found on their way not only to the most proximal rete testis but also a more distant rete testis from any stage VIII seminiferous epithelia. In vivo imaging demonstrated that the direction of the flagella of spermatozoa attached to the seminiferous epithelium was repeatedly reversed. The epithelium at the inner curve of the seminiferous tubule was shaken more actively and had fewer spermatozoa attached compared with the epithelium at the outer curve. Our results hence suggest that the luminal flow in the seminiferous tubules is repeatedly reversed and that this physical force helps spermatozoa to be released from Sertoli cells. In brief: Spermatozoa are released from Sertoli cells and flow in the seminiferous tubule to the rete testis. Our results suggest that the luminal flow in the tubules is repeatedly reversed and that this physical force helps spermatozoa release from the Sertoli cells.

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

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.

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

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.

Three-dimensional reconstruction of testis cords/seminiferous tubules.

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.

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

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.

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

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.

MTMR4, a phosphoinositide-specific 3'-phosphatase, regulates TFEB activity and the endocytic and autophagic pathways.

Phosphatidylinositol 3-phosphate (PI(3)P) is the predominant phosphoinositide species in early endosomes and autophagosomes, in which PI(3)P dictates traffic of these organelles. Phosphoinositide levels are tightly regulated by lipid-kinases and -phosphatases; however, a phosphatase that converts PI(3)P back to phosphatidylinositol in the endosomal and autophagosomal compartments is not fully understood. We investigated the subcellular distribution and functions of myotubularin-related protein-4 (MTMR4), which is distinct among other MTMRs in that it possesses a PI(3)P-binding FYVE domain, in lung alveolar epithelium-derived A549 cells. MTMR4 was localized mainly in late endosomes and autophagosomes. MTMR4 knockdown markedly suppressed the motility, fusion, and fission of PI(3)P-enriched structures, resulting in decreases in late endosomes, autophagosomes, and lysosomes, and enlargement of PI(3)P-enriched early and late endosomes. In amino acid- and serum-starved cells, MTMR4 knockdown decreased both autophagosomes and autolysosomes and markedly increased PI(3)P-containing autophagosomes and late endosomes, suggesting that the fusion with lysosomes of autophagosomes and late endosomes might be impaired. Notably, MTMR4 knockdown inhibited the nuclear translocation of starvation stress responsive transcription factor-EB (TFEB) with reduced expression of lysosome-related genes in starved cells. These findings indicate that MTMR4 is essential for the integrity of endocytic and autophagic pathways.

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

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 (sessions 1 and 2) consisting of SEPs and ERPs with somatosensory Go/No-go paradigms under two conditions (cold stress and control) on different days. In session 2, 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 (session 1) to 30.4 ± 0.9°C (session 2) 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: P < 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: P < 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.

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

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.

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

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.

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

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.