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Background: In the case of an unresectable malignant hilar biliary obstruction (MHBO), the optimal drainage method has not yet been established. Recently, an 8 mm, fully covered, self-expandable metal stent (FCSEMS) with an ultra-slim introducer has become available. In this article, the results of whole-liver drainage tests using this novel FCSEMS for MHBO are reported. Methods: Unresectable MHBOs up to Bismuth IIIa with strictures limited to the secondary branches were eligible. The proximal end of the stent was placed in such a way as to avoid blocking the side branches, and the distal end was placed above the papilla when possible. Consecutive patients treated between April 2017 and January 2021 were retrospectively analyzed. The technical and functional success rates, rates and causes of recurrent biliary obstruction (RBO), time to RBO (TRBO), revision for RBO, and adverse events (AEs) were evaluated. Results: Eleven patients (Bismuth I/II/IIIa: 1/7/3) were enrolled. Two stents were placed in nine patients and three were placed in two patients. Both the technical and functional success rates were 100%. RBO occurred in four (36%) patients due to sludge formation. Revision was performed for three patients, with the successful removal of all stents. The median TRBO was 187 days, and no late AEs other than the RBO occurred. Regarding the distal position of the stent, the RBO rate was significantly lower (14.3% vs. 75%, p = 0.041) and the cumulative TRBO was significantly longer (median TRBO: not reached vs. 80 days, p = 0.031) in the case of the placement above the papilla than the placement across the papilla. Conclusion: For unresectable MHBOs of Bismuth I, II, and IIIa, whole-liver drainage with a novel 8 mm FCSEMS possessing an ultra-slim introducer was feasible and potentially safe, with favorable stent patency. Placement above the papilla might be preferrable to placement across the papilla.

Currently, endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is widely performed worldwide for various benign and malignant biliary diseases in cases of difficult or unsuccessful endoscopic transpapillary cholangiopancreatography (ERCP). Furthermore, its applicability as primary drainage has also been reported. Although recent advances in EUS systems and equipment have made EUS-HGS easier and safer, the risk of serious adverse events such as bile leak and stent migration still exists. Physicians and assistants need not only sufficient skills and experience in ERCP-related procedures and basic EUS-related procedures such as fine needle aspiration and pancreatic fluid collection drainage, but also knowledge and techniques specific to EUS-HGS. This technical review mainly focuses on EUS-HGS with self-expandable metal stents for unresectable malignant biliary obstruction and presents the latest and detailed tips for safe and successful performance of the technique.

Background: Endoscopic-ultrasound-guided gastrojejunostomy (EUS-GJ) can be a new alternative for patients with malignant afferent loop syndrome (MALS). However, a fully covered self-expandable metal stent (FCSEMS) has not been well investigated in this setting. Methods: This is a multicenter retrospective cohort study. Consecutive patients that underwent EUS-GJ using a FCSEMS for MALS between April 2017 and November 2022 were enrolled. Primary outcomes were technical and clinical success rates. Secondary outcomes were adverse events, recurrent symptoms, and overall survival. Results: Twelve patients (median age: 67.5 years (interquartile range: 58–74.8); 50% male) were included. The most common primary disease and type of previous surgery were pancreatic cancer (67%) and pancreatoduodenectomy (75%), respectively. Technical success and clinical success were achieved in all patients. Procedure-related adverse events occurred in one patient (8%) with mild peritonitis. During a median follow-up of 96.5 days, one patient (8%) had recurrent symptoms due to the EUS-GJ stent dysfunction; including biliary events unrelated to the EUS-GJ stent, five patients (42%) had recurrent events. The median overall survival was 137 days. Nine patients (75%) died due to disease progression. Conclusions: EUS-GJ with a FCSEMS seems safe and effective for MALS with high technical and clinical success rates and an acceptable recurrence rate.

Dysfunctional dopamine signaling is implicated in various neuropsychological disorders. Previously, we reported that dopamine increases D1 receptor (D1R)-expressing medium spiny neuron (MSN) excitability and firing rates in the nucleus accumbens (NAc) via the PKA/Rap1/ERK pathway to promote reward behavior. Here, the results show that the D1R agonist, SKF81297, inhibits KCNQ-mediated currents and increases D1R-MSN firing rates in murine NAc slices, which is abolished by ERK inhibition. In vitro ERK phosphorylates KCNQ2 at Ser414 and Ser476; in vivo, KCNQ2 is phosphorylated downstream of dopamine signaling in NAc slices. Conditional deletion of Kcnq2 in D1R-MSNs reduces the inhibitory effect of SKF81297 on KCNQ channel activity, while enhancing neuronal excitability and cocaine-induced reward behavior. These effects are restored by wild-type, but not phospho-deficient KCNQ2. Hence, D1R-ERK signaling controls MSN excitability via KCNQ2 phosphorylation to regulate reward behavior, making KCNQ2 a potential therapeutical target for psychiatric diseases with a dysfunctional reward circuit.

Objectives: To investigate the efficacy of suppressing joint destruction with subcutaneous tocilizumab (TCZ-SC) for Japanese rheumatoid arthritis (RA) patients in the real-world clinical setting.Me...

The cortex contains multiple neuron types with specific connectivity and functions. Recent progress has provided a better understanding of the interactions of these neuron types as well as their output organization particularly for the frontal cortex, with implications for the circuit mechanisms underlying cortical oscillations that have cognitive functions. Layer 5 pyramidal cells (PCs) in the frontal cortex comprise two major subtypes: crossed-corticostriatal (CCS) and corticopontine (CPn) cells. Functionally, CCS and CPn cells exhibit similar phase-dependent firing during gamma waves but participate in two distinct subnetworks that are linked unidirectionally from CCS to CPn cells. GABAergic parvalbumin-expressing fast-spiking (PV-FS) cells, necessary for gamma oscillation, innervate PCs, with stronger and global inhibition to somata and weaker and localized inhibitions to dendritic shafts/spines. While PV-FS cells form reciprocal connections with both CCS and CPn cells, the excitation from CPn to PV-FS cells exhibits short-term synaptic dynamics conducive for oscillation induction. The electrical coupling between PV-FS cells facilitates spike synchronization among PV-FS cells receiving common excitatory inputs from local PCs and inhibits other PV-FS cells via electrically communicated spike afterhyperpolarizations. These connectivity characteristics can promote synchronous firing in the local networks of CPn cells and firing of some CCS cells by anode-break excitation. Thus subsets of L5 CCS and CPn cells within different levels of connection hierarchy exhibit coordinated activity via their common connections with PV-FS cells, and the resulting PC output drives diverse neuronal targets in cortical layer 1 and the striatum with specific temporal precision, expanding the computational power of the cortical network.

Highlight Endoscopic ultrasound-guided hepaticogastrostomy with a partially covered metal stent has a potential risk of stent occlusion due to hyperplasia at an uncovered portion of the stent. Matsubara and colleagues report that radiofrequency ablation of hyperplasia with additional placement of an uncovered metal stent is useful for preventing recurrent stent occlusion.

Feedback projections from the secondary motor cortex (M2) to the primary motor and sensory cortices are essential for behavior selection and sensory perception. Intratelencephalic (IT) cells in layer 5 (L5) contribute feedback projections to diverse cortical areas. Here we show that L5 IT cells participating in feedback connections to layer 1 (L1) exhibit distinct projection patterns, genetic profiles, and electrophysiological properties relative to other L5 IT cells. An analysis of the MouseLight database found that L5 IT cells preferentially targeting L1 project broadly to more cortical regions, including the perirhinal and auditory cortices, and innervate a larger volume of striatum than the other L5 IT cells. We found experimentally that in upper L5 (L5a), ER81 (ETV1) was found more often in L1-preferring IT cells, and in IT cells projecting to perirhinal/auditory regions than those projecting to primary motor or somatosensory regions. The perirhinal region-projecting L5a IT cells were synaptically connected to each other and displayed lower input resistance than contra-M2 projecting IT cells including L1-preferring and nonpreferring cells. Our findings suggest that M2-L5a IT L1-preferring cells exhibit stronger ER81 expression and broader cortical/striatal projection fields than do cells that do not preferentially target L1.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a valid modality for nodal lung cancer staging. The sonographic features of EBUS helps determine suspicious lymph nodes (LNs). To facilitate this use of this method, machine-learning-based computer-aided diagnosis (CAD) of medical imaging has been introduced in clinical practice. This study investigated the feasibility of CAD for the prediction of nodal metastasis in lung cancer using endobronchial ultrasound images. Image data of patients who underwent EBUS-TBNA were collected from a video clip. Xception was used as a convolutional neural network to predict the nodal metastasis of lung cancer. The prediction accuracy of nodal metastasis through deep learning (DL) was evaluated using both the five-fold cross-validation and hold-out methods. Eighty percent of the collected images were used in five-fold cross-validation, and all the images were used for the hold-out method. Ninety-one patients (166 LNs) were enrolled in this study. A total of 5255 and 6444 extracted images from the video clip were analyzed using the five-fold cross-validation and hold-out methods, respectively. The prediction of LN metastasis by CAD using EBUS images showed high diagnostic accuracy with high specificity. CAD during EBUS-TBNA may help improve the diagnostic efficiency and reduce invasiveness of the procedure.

In the management of patients with pancreatic cancer and cholangiocarcinoma, various issues other than antitumor therapy will develop: obstructive jaundice due to the tumor invasion to the bile duct or the biliojejunal anastomotic stricture after pancreatoduodenectomy; recurrent pancreatitis or pancreatic pain due to the pancreatojejunal anastomotic stricture after pancreatoduodenectomy; cholecystitis due to the placement of biliary self-expandable metal stents; postoperative pancreatic fistulas with or without peripancreatic fluid collections, and severe abdominal pains due to the tumor invasion to the celiac plexus. Traditionally, endoscopic transpapillary or percutaneous approaches were applied for the treatment of such problems; however, they have many limitations in the success and the quality of life of patients. To date, endoscopic ultrasound (EUS)-guided interventions have emerged to resolve these issues as minimally invasive therapies. In this chapter, EUS-guided interventional procedures in the management of pancreatic cancer and cholangiocarcinoma will be described.

Background: The selection of an approach route in endoscopic ultrasound-guided rendezvous (EUS-RV) for failed biliary cannulation is complicated. We proposed an algorithm for EUS-RV. Methods: We retrospectively evaluated consecutive EUS-RV cases between April 2017 and July 2020. Puncturing the distal extrahepatic bile duct (EHBD) from the duodenal second part (D2) (DEHBD/D2 route) was attempted first. If necessary, puncturing the proximal EHBD from the duodenal bulb (D1) (PEHBD/D1 route), puncturing the left intrahepatic bile duct (IHBD) from the stomach (LIHBD/S route), or puncturing the right IHBD from the D1 (RIHBD/D1 route) were attempted in this order. Results: A total of 16 patients were included. The DEHBD/D2 route was used in 10 (62.5%) patients. The PEHBD/D1 route was attempted in five (31.3%) patients, and the biliary puncture failed in one patient in whom the RIHBD/D1 route was used because of tumor invasion to the left hepatic lobe. The LIHBD/S route was applied in one (6.3%) patient. Successful biliary cannulation was achieved in all patients eventually. The time from the puncture to the guidewire placement in the DEHBD/D2 route (3.5 min) was shorter than that in other methods (14.0 min) (p = 0.014). Adverse events occurred in one (6.3%) patient with moderate pancreatitis. Conclusions: The proposed algorithm might be useful for the selection of an appropriate approach route in EUS-RV.

Background: Posttraumatic stress disorder (PTSD) has been associated with increased inflammation. C-reactive protein (CRP) is a marker of systemic inflammation, and recently, single nucleotide polymorphisms (SNPs) in the CRP gene have been associated with increased blood CRP protein levels and illness severity in PTSD patients. However, the mechanism by which the CRP SNPs are involved in PTSD remains unclear. Here we investigated the association of CRP genetic variation with blood proinflammatory protein levels, symptomatology, and cognitive function, and further explored the moderating effect of childhood maltreatment history, in adult patients with PTSD. Methods: Fifty-seven Japanese civilian women with PTSD and 73 healthy control women were enrolled. Three SNPs in the CRP gene, namely rs2794520, rs1130864, and rs3093059, were genotyped, and analyses focused on rs2794520 (T/C). Serum levels of high-sensitivity CRP (hsCRP), high-sensitivity tumor necrosis factor-α (hsTNF-α), and interleukin-6 were measured. PTSD symptoms were evaluated by the Posttraumatic Diagnostic Scale. Cognitive function was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status. Childhood maltreatment history was assessed by the Childhood Trauma Questionnaire. Results: Patients with the rs2794520 CC/CT genotype, compared to those with the TT genotype, showed significantly higher levels of hsCRP (p=0.009) and hsTNF-α (p=0.001), more severe PTSD symptoms (p=0.036), and poorer cognitive function (p=0.018). A two-way analysis of variance revealed a significant genotype-by-maltreatment interaction for more severe PTSD avoidance symptom (p=0.012). Limitations: The relatively small sample size limited our findings. Conclusions: These findings may provide an insight into the etiology of PTSD from the inflammatory perspective.

We have found that cross-coupling between aryl Grignard reagents and allylic methyl ethers proceeded well in the presence of a catalytic amounts of Fe(acac)3 to afford the corresponding allylic substitution products in good yields. Under the same conditions, allylic trimethylsilyl ethers also reacted with Grignard reagents to give the corresponding cross-coupling products.

Abatacept may exert its clinical effect on rheumatoid arthritis (RA) by suppressing anti-cyclic citrullinated peptide (CCP) antibody production. This study was undertaken to test this hypothesis by examining the changes of disease activity of RA and anti-CCP antibody levels over time after starting abatacept. Sixty Japanese RA patients who started abatacept were included in this multicenter, prospective observational study. Simple Disease Activity Index (SDAI) and anti-CCP antibody levels were evaluated at 12, 24, and 52 weeks. The mean SDAI score significantly decreased within 12 weeks after starting abatacept and was maintained thereafter. On the contrary, the mean anti-CCP antibody levels did not change until 52 weeks. At the individual level, there were substantial changes of anti-CCP antibody levels, but these were not correlated with the changes of disease activity at any time points. Thus, abatacept reduces the disease activity of RA independently of modulating anti-CCP antibody production.

This paper reports an investigation of the effects of silica particles contained in mold resin to the light extraction efficiency of light-emitting diode (LED) packaging (PKG) using ray-tracing simulations. The light extraction efficiencies, namely, luminous and radiant flux of the rays emitted from the PKG, are improved with the silica particles. The silica particles cause the scattering of the rays in the mold resin of the LED PKG. If the scattering can be generated properly, the light extraction efficiency can be improved. Varying the volume percentage of the silica particles, its effects to the light extraction efficiency are confirmed. Finally, we could confirm the improvement of luminous higher than 0.5 lm and radiant flux higher than 0.02 W respectively from the simulation results.

This study aimed to evaluate the remission in rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ), based on prospectively registered data in clinical practice.We studied 114 consecutive RA patients treated with TCZ for an average of 3.5 years. Remission was evaluated by using the EULAR criteria and the new ACR/EULAR Boolean-based criteria.Among 114 patients (average age 52.2 years; average disease duration 10.6 years), 76 (67 %) had previously received anti-TNF biologics. Mean baseline DAS28-ESR of 5.4 and improved to 2.4 at 36 months. Overall, DAS28-ESR2.6 was attained by 66.7 %, while ACR/EULAR remission was attained by 35.1 %. ACR/EULAR remission rate was significantly higher in the patients who were biologics-naïve and had good response at the first month. Among 23 patients who completed the treatment for 3 years and had ACR/EULAR remission at 1 year, 15 (65 %) remained in the remission and 16 (70 %) had a DAS28-ESR2.6 at the final follow-up. The retention rate at 36 months was 68.2 %.In patients with RA, TCZ is highly effective for both biologics-naïve patients and patients previously exposed to biologics, achieving a high remission rate and drug continuation rate (68.2 %) in clinical practice.

The reactions of aroyl chlorides with the lithium phosphoranide generated from bis(naphth-1,8-diyl-8-oxy)phosphorane 1 afforded aroylspirophosphoranes 3a – f. The p-anisoyl- and p-tert-butylbenzoylphosphoranes 3a and 3b bearing an electron-donating aryl group were stable to moisture on silica gel. The crystal structures of p-anisoyl-, p-tert-butylbenzoyl-, benzoyl-, and p-fluorobenzoylphosphorane (3a, 3b, 3d, and 3e) elucidated by X-ray structural analysis suggested effective intramolecular np(Oapical)→π∗(C O) charge transfer stabilization to be operative.

Cortical fast-spiking (FS) interneurons are electrically interconnected through gap junctions and form dendritic net structures extending over different functional columns. Here we investigated how pyramidal cells regulate FS cell network activity. Using paired recordings and glutamate puff stimulations, we found that FS cell pairs connected by electrical synapses shared common inputs from surrounding pyramidal cells more frequently than those unconnected or connected only by chemical synapses. Experimental and simulation results suggest that activity spread evoked by common inputs to electrically connected FS cells depends on network state. When cells were in the depolarized state, common inputs to electrically connected cells enhanced spike induction and induced inhibitory effects in surrounding FS cells. By contrast, in the hyperpolarized state, either sub- or suprathreshold inputs produced depolarizing potentials in nearby cells. Our results suggest that globally connected FS cell networks are locally regulated by pyramidal cells in an electrical connection- and network state-dependent manner.

Microstructures and hardness of a Fe–1.4%Cr–1%C pearlitic steel processed by super-rapid induction heating-and-quenching (SRIHQ) under various conditions have been investigated. A nano-scaled laminated microstructure composed of two different types of martensite (highly-twinned or containing a high dislocation density) was formed and the maximum hardness was obtained by heating to 1223 K in 0.5 s and quenched. Electron energy loss spectroscopy indicated that the two different types of martensite were formed depending on the local solute-concentration in the non-uniform solute-distribution realized by the SRIHQ-process.

Higher-order motor cortices, such as the secondary motor area (M2) in rodents, select future action patterns and transmit them to the primary motor cortex (M1). To better understand motor processing, we characterized "top-down" and "bottom-up" connectivities between M1 and M2 in the rat cortex. Somata of pyramidal cells (PCs) in M2 projecting to M1 were distributed in lower layer 2/3 (L2/3) and upper layer 5 (L5), whereas PCs projecting from M1 to M2 had somata distributed throughout L2/3 and L5. M2 afferents terminated preferentially in upper layer 1 of M1, which also receives indirect basal ganglia output through afferents from the ventral anterior and ventromedial thalamic nuclei. On the other hand, M1 afferents terminated preferentially in L2/3 of M2, a zone receiving indirect cerebellar output through thalamic afferents from the ventrolateral nucleus. While L5 corticopontine (CPn) cells with collaterals to the spinal cord did not participate in corticocortical projections, CPn cells with collaterals to the thalamus contributed preferentially to connections from M2 to M1. L5 callosal projection (commissural) cells participated in connectivity between M1 and M2 bidirectionally. We conclude that the connectivity between M1 and M2 is directionally specialized, involving specific PC subtypes that selectively target lamina receiving distinct thalamocortical inputs.

Our previous study reported a frequent detection of human papillomavirus (HPV) genome in primary lung adenocarcinomas of the recurrent patients who were responsive to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, suggesting that HPV presence in lung cancer may be related to a genetic background related to EGFR mutations. The present study examined the association between the HPV presence and mutations in exons 19 and 21 of EGFR gene in Japanese lung cancer patients. Thirteen (31%) out of 42 cases had EGFR mutations. Although these mutations were tended to be observed in females, non-smokers, or adenocarcinomas, there was no statistically significant associations. HPV DNA was found in 7/42 (17%) lung tumors. The frequency of HPV presence did not differ in histological types. The presence of HPV DNA was significantly related to EGFR mutations (P=0.021), especially in adenocarcinomas of the lung (P=0.014). HPV-positive lung tumors accounted for 38% and 7% of those with and without EGFR mutations, respectively. Our results suggest that EGFR mutations are associated with HPV presence in Japanese patients with lung cancer.

Development of new analytical tools for nanostructures directly contributes to the study of catalysts. By using scanning electron microscopy (SEM) with a newly designed signal enhancer, we study cubic and truncated octahedral cerium oxide (CeO(2)) nanoparticles, which are composed of smaller primary octahedral CeO(2) and are formed through bond formation with hexanedioic acid. The signal enhancer is designed to efficiently collect secondary electrons of kinetic energy less than 10 eV; thus, it greatly improves the S/N ratio. On the basis of the observed SEM images and electron backscattered diffraction patterns of the cross section of the nanoparticles, we discuss the formation mechanism of the nanoparticles and speculate that the primary CeO(2) nanocrystals share their edges in the cubic nanoparticles and truncated octahedral nanoparticles. These results will contribute to the preparation of nanostructured metal oxide surfaces with controlled morphologies that could enhance catalytic activity.

Blue-emitting luminescent polymer nanocomposites were prepared from 1,3-diketone functionalized poly(methyl methacrylate) (PMMA) and zirconium oxide nanocrystals (ZrO2-NCs). Fourier transform infrared spectra suggested chemisorption of the 1,3-diketone by bidentate chelation of the diketonate anion to the ZrO2-NC surface. The ZrO2-NCs were well dispersed in the polymer matrix and crosslinked on the NC surfaces. The chemically crosslinked polymer nanocomposites had high photostability compared with the PMMA/ZrO2-NC composites with 1,3-bis(4-methoxyphenyl)-1,3-propanedione. The stability of the luminescence from the polymer nanocomposites was enhanced because the 1,3-diketonate binding sites were fixed between inorganic NCs and polymer chains. The blue emission peaking at 448 nm can be tuned by the addition of 8-hydroxyquinoline-containing copolymer/ZrO2-NC composite, which red-shifted the emission from blue to yellow and green as a function of the blend composition. This strategy, in which the ligand would be immobilized by an organic/inorganic sandwich structure, is suitable for obtaining not only well-stabilized luminescent nanocomposites but also nano-optoelectronics with controlled emission colors. 1,3-Diketone moiety fixed between organic polymer and inorganic nanocrystal imitated sandwich-like structure can provide highly stabilized luminescent materials featuring luminescent stability, durability and emission color tuning ability.

Well-defined poly(N-isopropylacrylamide)s (PNIPAMs) with boron dipyrromethene (BODIPY) in the terminal end were prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization of NIPAM with BODIPY-chain transfer agent (CTA), which was synthesized by the reaction of pyrrole and BODIPY derivative having benzyl chloride in the meso position. The controlled character of the polymerization of NIPAM was confirmed by the formation of the narrow molecular weight distribution products and linear increase of molecular weight with the feed ratios of [NIPAM]/[CTA]. The RAFT-prepared PNIPAM exhibited strong green luminescence with emission maxima at 558 nm upon excitation with the absorption maxima at 526 nm and was used for the aqueous synthesis of stabilized gold nanoparticles (AuNPs). The in situ reduction of the RAFT-prepared polymers and HAuCl(4) resulted in the formation of stable modified AuNPs with size distributions of ∼10 nm in water solution. Temperature-dependent change in photoluminescence (PL) spectra (excited at 526 nm) of the RAFT-prepared polymers measured in water showed an increase in emission intensity with the rise at temperature (20 → 40 °C). On the contrary, AuNPs exhibited a decrease in emission intensity with increasing of temperature, resulting that shrinking of the distance between BODIPY units and Au core in the AuNP across border LCST gives rise to both quenching of emission of BODIPY unit by Förster resonance energy transfer (FRET) and dye quenching of aggregated BODIPY units. The emission/quenching of AuNP occurs reversibly and efficiently, regardless of the heating and cooling cycle.

Highly transparent and homogeneous hybrids containing a single nano-sized inorganic oxide domain were synthesized from poly(methyl methacrylate) (PMMA) and aqueous dispersed zirconium oxide nanocrystals (ZrO2-NCs) in the presence of a coupling agent, 3-(methacryloxy)propyl-trimethoxysilane (MPTS), which was grafted onto the surface of ZrO2-NCs by zirconium hydroxide (Zr-OH) surface groups. The surface-functionalized ZrO2-NCs were used as macromonomers in the process of grafting from polymerization of methyl methacrylate (MMA). The densities of surface Zr-OH groups and MPTS surface modifications were determined using thermogravimetric analysis. Fourier transform infrared analysis indicated successful bonding between organic and inorganic moieties. The morphology of the obtained hybrid films was investigated by scanning electron microscopy and tapping-mode atomic force microscopy. Hybrid films possess interesting thermal stability and optical transparency characteristics because of the uniform incorporation of networks between organic polymer chains and inorganic nanocrystals. Transparent and homogeneous hybrids were synthesized from poly(methyl methacrylate) (PMMA) and aqueous dispersed zirconium oxide nanocrystals (ZrO2-NCs) with a coupling agent, 3-(methacryloxy)propyltrimethoxysilane (MPTS). The covalent bonding between PMMA- and MPTS-modified ZrO2 nanocrystals is crucial to obtain nanoscale dispersed hybrid materials. The hybrid films retained good optical transparency compared with that of PMMA/ZrO2 blend composites and will be promisingly applied for optical functional materials and coatings.

Transparent and homogeneous organic–inorganic hybrids with poly(vinylidene fluoride) (PVdF) could be prepared by addition of zirconium oxide nanocrystals (ZrO2-NCs) in a polar aprotic solvent and the subsequent solvent evaporation. The polar aprotic solvents such as DMF, DMAc and DMSO would form hydrogen bonds with Zr-OH groups of the ZrO2-NC and play a role as compatibilizers between the PVdF and ZrO2-NCs. The interpenetration between PVdF and ZrO2-NCs resulted in the nanometer dispersion of PVdF chains in a ZrO2-NC matrix. High dosage of the ZrO2-NCs as physical inhibitors between PVdF polymer chains sufficiently prevented the PVdF chain mobility in the internal of hybrids. The transparency of the PVdF/ZrO2-NC hybrids was dramatically improved by controlling the content of ZrO2-NCs. Novel multifunctional hybrids with high transparency, high refractive index and good mechanical property were obtained by hybridization of PVdF and ZrO2-NCs.

Hybridization of amphiphilic polymer and inorganic nanocrystal was examined aiming for improvement of thermal and optical properties of the organic polymer used. Optically transparent and homogeneous hybrids of poly(vinylpyrrolidone) (PVP) and zirconium oxide nanocrystals (ZrO2-NCs) were prepared through a water/methanol solution. Hydrogen bonding interactions between amide groups of PVP and Zr-OH groups from ZrO2-NC were confirmed in the hybrids obtained. Thermal properties of the hybrids were improved with an increase of the ZrO2-NC content. In this research, ZrO2–NCs in PVP matrix showed fine dispersion state. As expected, refractive index of the hybrids increased with ZrO2-NC concentration and the refractive index variations follow the Lorentz–Lorenz relation.

Reactive oxygen species (ROS)-related membrane lipid peroxidation in the root of Arabidopsis thaliana was fluorescently visualized and investigated under salt stress. In the control roots without salt stress, more fluorescence was observed in the elongating region than in the meristematic region. Salt stress of 100 mM NaCl enhanced the fluorescence in both, indicating that salt stress-induced ROS, and consequently membrane lipid peroxidation. In transgenic tobacco glutathione S -transferase over-expressing Arabidopsis (the parB plants), less fluorescence was observed than in the non-transgenic control plants. In the salt-stressed parB plant roots, the fluorescent brightness was reduced to 46% of that of the non-transgenic plant in the meristematic region. However, the inhibition of root growth was not improved in parB plants under salt stress at pH 5.7. That is, 100 mM of salt stress reduced the root growth to 40% or less both in the parent control plants and the parB plants. The root tissue osmotic pressure was almost the same between the two tested lines, which may be one of the reasons why no difference was observed in root growth between the two lines. These results suggested that salt stress-induced oxidative stress, and the introduction/over-expression of a glutathione S -transferase gene may have reduced the amount of ROS but the removal of ROS was not sufficient to effect salt tolerance because salt stress also caused an osmotic imbalance reducing the root growth.

Autoimmune regulator (AIRE) gene is a responsible gene for the rare autosomal recessive autoimmune disease: autoimmune-polyendocrinopathy-candidiasis ectodermal dystrophy (APECED). Although it has been reported that AIRE is expressed in the thymic epithelial cells and monocyte-dendritic cell lineage, the regulatory mechanisms of AIRE gene expression have as yet been poorly understood. Here we show that the expression of AIRE gene was induced in granulo-monocyte colony stimulating factor (GM-CSF)-stimulated myelomonocytic leukemia OTC-4 cells. In GM-CSF-stimulated OTC-4 cells, stat5 was not phosphorylated, while mitogen-activated protein kinases (MAPKs), including MAPK kinase (MEK) 1/2 and p38 MAPK, were phosphorylated, indicating activation of MAPK pathway. In addition, the expression of AIRE gene was inhibited by specific p38 MAPK inhibitor (SB203580), whereas the expression was rather enhanced by the MEK1/2 inhibitor (U0126), suggesting that AIRE gene expression is regulated by mitogen-activated protein kinase pathway.

The majority of excitatory synapses in the mammalian brain form on filopodia and spines, actin-rich membrane protrusions present on neuronal dendrites. The biochemical events that induce filopodia and remodel these structures into dendritic spines remain poorly understood. Here, we show that the neuronal actin- and protein phosphatase-1–binding protein, neurabin-I, promotes filopodia in neurons and nonneuronal cells. Neurabin-I actin–binding domain bundled F-actin, promoted filopodia, and delayed the maturation of dendritic spines in cultured hippocampal neurons. In contrast, dimerization of neurabin-I via C-terminal coiled-coil domains and association of protein phosphatase-1 (PP1) with neurabin-I through a canonical KIXF motif inhibited filopodia. Furthermore, the expression of a neurabin-I polypeptide unable to bind PP1 delayed the maturation of neuronal filopodia into spines, reduced the synaptic targeting of AMPA-type glutamate (GluR1) receptors, and decreased AMPA receptor-mediated synaptic transmission. Reduction of endogenous neurabin levels by interference RNA (RNAi)-mediated knockdown also inhibited the surface expression of GluR1 receptors. Together, our studies suggested that disrupting the functions of a cytoskeletal neurabin/PP1 complex enhanced filopodia and impaired surface GluR1 expression in hippocampal neurons, thereby hindering the morphological and functional maturation of dendritic spines.

Because the subthalamic nucleus (STN) acts as a driving force of the basal ganglia, it is important to know how the activities of STN neurons are regulated. Previously, we have reported that a subset of STN neurons generates a plateau potential in a voltage-dependent manner. These plateau potentials can be evoked only when the cell is hyperpolarized. Here, to examine the mechanism of the voltage-dependent generation of the plateau potential in STN neurons, we constructed a conductance-based model of the plateau-generating STN neuron based on experimental observations and compared simulation results with recordings in slices. The model consists of a single compartment containing a Na+ current, a delayed-rectifier K+ current, an A-type K+ current, an L-like long-lasting Ca2+ current, a T-type Ca2+ current, a Ca2+-dependent K+ current, and a leak current. Our simulation results showed that a plateau potential in the model could be induced in a voltage-dependent manner that depended on the inactivation properties of L-like long-lasting Ca2+ current. The model could also reproduce the generation of a plateau potential as a rebound potential after termination of hyperpolarizing current injection. In addition, we tested the stability of simulated plateau potentials against inhibitory perturbation and found that the model showed similar properties observed for the plateau potentials of STN neurons in slices. The effects of K+ channel blockade by TEA and intracellular Ca2+ ion chelation by BAPTA on the plateau duration were also tested in the model and were found to match experimental observations. Thus our STN neuron model could qualitatively reproduce a number of experimental observations on plateau potentials. Our results suggest that the inactivation of L-type Ca2+ channels plays an important role in the voltage-dependent generation of the plateau potential.

We describe a case of hypertrophic cranial pachymeningitis (HCP) associated with Wegener’s granulomatosis (WG) in a 60-year-old man presenting with chronic headache and multiple cranial nerve neuropathies. A test for antibodies to the neutrophil cytoplasmic protein myeloperoxidase (MPO-ANCA) was positive in this case. We review the literature on perinuclear (p)-ANCA-related HCP, including our case. This case indicates the link between MPO-ANCA-positive WG and HCP.