Massive pulmonary thrombosis caused by a popliteal venous aneurysm: A case report.

A venous aneurysm is characterized by a localized dilated lesion in most major veins. Popliteal venous aneurysms (PVAs) are rare; however, they are one of the causes of deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE), which can be critical due to the high mortality risk. We present a 21-year-old woman without prior medical history, who arrived by ambulance after having a transient cardio-pulmonary arrest. Contrast computed tomography revealed a massive PTE and a right PVA with a thrombus. Laboratory data suggested that she had no thrombotic predisposition. Therefore, we diagnosed her condition as a massive PTE that derived from a thrombus, which arose from the right PVA. After successful intravenous thrombolysis of the PTE and DVT, surgical plication of the right PVA was performed to prevent the recurrence of PTE. She has had no recurrence of PTE or DVT two years after surgical treatment. This case suggests that surgical plication might be an effective way of preventing recurrence in patients with PVA. Learning objective: Popliteal venous aneurysm (PVA) occurrence is rare, but it can result in deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE). To treat our patient who suffered transient cardiac-pulmonary arrest caused by a massive PTE, we first used a recombinant tissue plasminogen activator and anticoagulant therapy. After the condition was stabilized, surgical plication of the right PVA was performed to prevent DVT recurrence. The present case suggests that surgical plication might be beneficial.

Zinc supplementation in patients with acute myocardial infarction.

This single-centre prospective feasibility study (UMIN000030232) evaluated whether zinc supplementation was safe and effective for improving outcomes among patients with acute myocardial infarction (AMI). Within 24 h after successful primary percutaneous coronary intervention, consenting patients with AMI were randomly assigned 1:1 to receive conventional treatment (conventional treatment group) or conventional treatment plus zinc acetate supplementation (zinc supplementation group). The two groups were compared in terms of major adverse cardiovascular events (MACE), and scar size, which was evaluated using cardiac magnetic resonance imaging (CMR) at 4 weeks after discharge. A total of 56 patients underwent randomization (with 26 assigned to the zinc supplementation group and 27 to the conventional treatment group). The two groups had generally similar laboratory findings and clinical characteristics. The two groups also had similar lengths of hospital stay and rates of MACE. Forty of the 53 patients underwent CMR and it revealed that % core zone was numerically lower in the zinc supplementation group than in the conventional treatment group (9.3 ± 6.9% vs. 14.2 ± 9.1%, P = 0.07). This small single-centre study failed to detect a significant reduction in mid-term MACE after AMI among patients who received zinc supplementation.

Relationship between early drop in systolic blood pressure, worsening renal function, and in-hospital mortality in patients with heart failure: a retrospective, observational study.

This study aimed to determine the optimal cut-off value of the early drop in systolic blood pressure (SBP) for worsening renal function (WRF) in hospitalized patients with heart failure (HF) and analyze predictors of WRF and the early drop in SBP at that threshold. We retrospectively enrolled 396 patients with acute decompensated HF. The early drop in SBP was defined as the difference between baseline and SBP measured 24 h after hospitalization. We performed receiver operating characteristic (ROC) analysis to determine the optimal cut-off value of the early drop in SBP for WRF and evaluated the effect of the early drop in SBP on in-hospital mortality by multivariate logistic regression analyses. The mean age of the patients was 73.4 ± 14.7 years, and 61.2% were men. A 14.0% drop in SBP was identified as the optimal cut-off value for WRF from the ROC curve analysis. An early drop in SBP ≥ 14.0% was associated with WRF in multivariate logistic regression analysis (odds ratio 7.84; 95% confidence interval 4.06-15.14; P < 0.0001). The dose of intravenous furosemide within 24 h of admission was one of the predictors of the early drop in SBP ≥ 14.0%, while no early drop in SBP was a predictor of in-hospital mortality in multivariate logistic regression models. In conclusion, the optimal cut-off value for WRF in patients with HF was a 14.0% drop in SBP within 24 h of admission. The early drop in SBP ≥ 14.0% was one of the predictors of WRF in patients with HF. However, no early drop in SBP was associated with in-hospital mortality. This study was registered with the University Hospital Medical Information Network in Japan (UMIN000035989).

Boundary condition analysis of first and second order topological insulators.

We analytically study boundary conditions of the Dirac fermion models on a lattice, which describe the first and second order topological insulators. We obtain the dispersion relations of the edge and hinge states by solving these boundary conditions, and clarify that the Hamiltonian symmetry may provide a constraint on the boundary condition. We also demonstrate the edge-hinge analog of the bulk-edge correspondence, in which the nontrivial topology of the gapped edge state ensures gaplessness of the hinge state.

The phosphorylation status of NONPHOTOTROPIC HYPOCOTYL3 affects phot2-dependent phototropism in Arabidopsis.

The blue light photoreceptors, phototropin 1 (phot1) and phot2, and their signal transducer, NONPHOTOTROPIC HYPOCOTYL3 (NPH3), are activators of the phototropic responses of Arabidopsis hypocotyls. In a recent study, we reported that the control of NPH3 phosphorylation at serine 7 (S7: or S5), S213, S223, S237, S467, S474 (or S476), and S722 (or S723) contributes to the photosensory adaptation of phot1 signaling during the phototropic response. Phosphomimetic NPH3SE mutant and unphosphorylatable NPH3SA mutant on those serine residues function efficiently under blue light conditions at fluence rates of 10-5 µmol m-2 s-1 and 10-3 µmol m-2 s-1 or more, respectively. We here demonstrate that phosphomimetic NPH3SE, but not unphosphorylatable NPH3SA, promotes phot2-dependent phototropism under blue light condition at 100 µmol m-2 s-1. This result suggests that phot1 negatively controls phot2 signaling through the dephosphorylation of NPH3 at those residues and that the hyperactivation of phot1- and phot2-NPH3 complexes does not occur at the same time under high intensity blue light. We hypothesize that the dephosphorylation of NPH3 on those serine residues suppresses both phot1 and phot2 signaling, which results in different impacts on phot1- and phot2-dependent hypocotyl phototropism due to the differences in the photosensitivity and activation levels of phot1 and phot2.

Phosphorylation of NONPHOTOTROPIC HYPOCOTYL3 affects photosensory adaptation during the phototropic response.

Photosensory adaptation, which can be classified as sensor or effector adaptation, optimizes the light sensing of living organisms by tuning their sensitivity to changing light conditions. During the phototropic response in Arabidopsis (Arabidopsis thaliana), the light-dependent expression controls of blue-light (BL) photoreceptor phototropin 1 (phot1) and its modulator ROOT PHOTOTROPISM2 (RPT2) are known as the molecular mechanisms underlying sensor adaptation. However, little is known about effector adaption in plant phototropism. Here, we show that control of the phosphorylation status of NONPHOTOTROPIC HYPOCOTYL3 (NPH3) leads to effector adaptation in hypocotyl phototropism. We generated unphosphorable and phosphomimetic NPH3 proteins on seven phosphorylation sites in the etiolated seedlings of Arabidopsis. Unphosphorable NPH3 showed a shortening of its retention time in the cytosol and caused an inability to adapt to very low fluence rates of BL (∼10-5 µmol m-2 s-1) during the phototropic response. In contrast, the phosphomimetic NPH3 proteins had a lengthened retention time in the cytosol and could not enable the adaptation to BL at fluence rates of 10-3 µmol m-2 s-1 or more. Our results indicate that the activation level of phot1 and the corresponding phosphorylation level of NPH3 determine the dissociation rate and the reassociation rate of NPH3 on the plasma membrane, respectively. These mechanisms may moderately maintain the active state of phot1 signaling across a broad range of BL intensities and contribute to the photosensory adaptation of phot1 signaling during the phototropic response in hypocotyls.

Analgesic Effect of Combined Therapy with the Japanese Herbal Medicine "Yokukansan" and Electroacupuncture in Rats with Acute Inflammatory Pain.

Background: Japanese herbal medicine, called Kampo medicine, and acupuncture are mainly used in Japanese traditional medicine. In this experiment, the analgesic effect of Yokukansan (YKS) alone and a combination of YKS and electroacupuncture (EA) on inflammatory pain induced by formalin injection were examined. Methods: Animals were divided into four groups: a control group, formalin injection group (formalin), YKS-treated formalin group (YKS), and YKS- and EA-treated formalin group (YKS + EA). The duration of pain-related behaviors and extracellular signal-regulated protein kinase (ERK) activation in the spinal cord after formalin injection in the right hind paw were determined. Results: The duration of pain-related behaviors was dramatically prolonged in the late phase (10-60 min) in the formalin group. The YKS treatment tended to reduce (p = 0.08), whereas YKS + EA significantly suppressed the pain-related behaviors (p < 0.01). Immunohistochemical and Western blot analyses revealed that the number of phosphorylated ERK1/2 (pERK1/2)-positive cells and the pERK expression level, which were increased by formalin injection, were significantly inhibited by YKS (p < 0.05) and YKS + EA (p < 0.01). Conclusions: The YKS + EA combination therapy elicited an analgesic effect on formalin-induced acute inflammatory pain.

Takotsubo syndrome associated with autoimmune limbic encephalitis: a case report.

BACKGROUND: Central nervous system diseases are common triggers of Takotsubo syndrome. We herein report a rare case of Takotsubo syndrome associated with autoimmune limbic encephalitis. CASE PRESENTATION: A 68-year-old Japanese woman presented to our emergency room with disturbed consciousness. At admission, she showed hypoxemia. Left ventriculography showed akinesia in the middle part of the left ventricle and hyperkinesia in the apical and basal parts of the left ventricle, and the diagnosis of midventricular Takotsubo syndrome was established. However, after an improvement in disturbed consciousness and Takotsubo syndrome symptoms, her brother noticed something wrong with her behavior during his visit to the hospital. Subsequently, we consulted the neurology department 1 week after admission. Her brother revealed a history of abnormal behavior by the patient (such as mistaken entry in the wrong apartment in her building or in another person's car) a few days prior to the onset of disturbed consciousness, suggesting disorientation of place. Brain magnetic resonance imaging showed an increased signal in the medial aspect of the temporal lobes, which was most clearly observed on the fluid-attenuated inversion recovery sequence; additionally, a cerebrospinal fluid analysis revealed mild lymphocytic pleocytosis. Finally, we established a diagnosis of midventricular Takotsubo syndrome associated with autoimmune limbic encephalitis. CONCLUSIONS: It is presumed that the dysfunction of limbic system due to autonomic limbic encephalopathy is associated with exaggerated sympathetic stimulation. This likely resulted in Takotsubo syndrome in our patient.

Poor prognosis of heart failure patients with in-hospital worsening renal function and elevated BNP at discharge.

AIMS: Our purpose was to investigate the association between the B-type natriuretic peptide (BNP) level at discharge, the occurrence of worsening renal function (WRF), and long-term outcomes in patients with heart failure (HF). METHODS AND RESULTS: We enrolled hospitalized acute HF patients. We divided patients into four groups on the basis of BNP <250 pg/mL (BNP-) or BNP ≥250 pg/mL (BNP+) at discharge and the occurrence of WRF during admission: BNP-/WRF-, BNP-/WRF+, BNP+/WRF-, and BNP+/WRF+. We evaluated the association between BNP at discharge, WRF, and cardiovascular/all-cause mortality/hospitalization due to HF. Clinical follow-up was completed in 301 patients. At discharge, percentages of the patients with clinical signs of HF were low and similar among four groups. The median follow-up period was 1206 days (interquartile range, 733-1825 days). The composite endpoint of cardiovascular mortality and HF hospitalization was significantly different between the four groups [12.9% (BNP-/WRF-), 22.7% (BNP-/WRF+), 35.8% (BNP+/WRF-), and 55.4% (BNP+/WRF+), P < 0.0001]. All-cause mortality was also different etween the four groups (15.1%, 38.6%, 28.7%, and 39.3%, respectively, P = 0.003). In the multivariate Cox proportional hazards model, the combination of BNP ≥250 pg/mL and WRF showed the highest hazard ratio (HR) for composite endpoint (HR, 5.201; 95% confidence interval, 2.582-11.11; P < 0.0001), and BNP-/WRF+ was associated with increased all-cause mortality (HR, 2.286; 95% confidence interval, 1.089-4.875; P = 0.03). Patients in BNP+/WRF+ had a higher cardiovascular mortality (28.6%), and those in BNP-/WRF+ had a high non-cardiovascular mortality (29.5%). CONCLUSIONS: Heart failure patients with BNP ≥250 pg/mL at discharge and in-hospital occurrence of WRF had the highest risk for the composite endpoint (cardiovascular mortality and HF hospitalization) among groups.

Sublayered Thin Films of Hydrated Anion Exchange Ionomer for Fuel Cells Formed on SiO2 and Pt Substrates Analyzed by Neutron Reflectometry under Controlled Temperature and Humidity Conditions.

Anion-conductive ionomers are used for electrolyte membranes in membrane-electrode assemblies and for binders in catalyst layers in anion exchange membrane fuel cells (AEMFCs). The conformations of these ionomers as well as their water distribution are important for designing new efficient/durable anion-conductive ionomers for AEMFCs. For a deeper understanding of the distribution of deuterium oxide (D2O) as a function of depth, neutron reflectometry (NR) was carried out on thin films of an anion exchange ionomer, BAF-QAF, with a thickness of approximately 60 nm formed on a thermally formed SiO2 film on Si(100) and on a 20 nm Pt layer deposited on the SiO2 film at a temperature of 60 °C and relative humidities of 0, 50, 70, and 90%. Clear NR modulation was obtained under each condition. The NR data were fit very well with a three-sublayered model parallel to the substrate with different densities of BAF-QAF and D2O. The influence of the SiO2 and Pt substrates was observed not only at the BAF-QAF/substrate interface but also on the entire thin film. The D2O absorption/desorption behavior in each sublayer differed in the BAF-QAF films cast on SiO2 and Pt. The BAF-QAF/SiO2 interface was rather hydrophilic, while the BAF-QAF/Pt interface was very hydrophobic.

Retrospective Radiographic Study of Degenerative Joint Disease in Cats: Prevalence Based on Orthogonal Radiographs.

Feline degenerative joint disease (DJD) has been reported worldwide. Radiographic evidence, including that from single-plane radiographs, has been used for diagnosis in these reports, though orthogonal radiographs are generally required to diagnose DJD. However, more orthogonal radiographs are required for diagnosis. In this study, we investigated how many orthogonal radiographs are necessary to diagnose feline DJD among domestic short-haired cats. We analyzed the data from 101 cats for which the owners requested screening for arthritis. Orthogonal radiographs of appendicular and intervertebral joints were taken from the chest to the caudal side. Radiographs were then reviewed and graded by severity of DJD in each joint. Radiographic evidence of appendicular DJD was detected in 74.26% of 101 cats, of which 40.59% had intervertebral DJD (typically of the lumbosacral joint). Appendicular DJD was most common in elbow joints. Lameness was recognized by an owner of two cats and was diagnosed by a veterinarian in two cats. No obvious pain was detected on palpation in any cats with appendicular osteoarthritis, but lumbosacral DJD was associated with back pain in seven cases. Aging was associated with radiographic evidence of DJD: radiographic evidence of DJD was observed in most older domestic short-haired cats. Most cases without lumbosacral DJD had no obvious symptoms. As the lifespan of cats increases due to better lifestyles, diet, and medical treatment, lumbosacral DJD, which is more likely in older cats, may become an increasingly important clinical problem. In addition, orthogonal radiograph must be taken to make diagnosis for appendicular joint DJD especially hip and stifle joint.

Arabidopsis ROOT PHOTOTROPISM2 Is a Light-Dependent Dynamic Modulator of Phototropin1.

The Arabidopsis (Arabidopsis thaliana) blue light photoreceptor phototropin1 (phot1) is a blue light-activated Ser/Thr protein kinase that mediates various light responses, including phototropism. The function of phot1 in hypocotyl phototropism is dependent on the light induction of ROOT PHOTOTROPISM2 (RPT2) proteins within a broad range of blue light intensities. It is not yet known however how RPT2 contributes to the photosensory adaptation of phot1 to high intensity blue light and the phototropic responses under bright light conditions. We show that RPT2 suppresses the activity of phot1 and demonstrate that RPT2 binds to the PHOT1 light, oxygen or voltage sensing1 (LOV1) domain that is required for its high photosensitivity. Our biochemical analyses revealed that RPT2 inhibits autophosphorylation of phot1, suggesting that it suppresses the photosensitivity and/or kinase activity of phot1 through the inhibition of LOV1 function. We found that RPT2 proteins are degraded via a ubiquitin-proteasome pathway when phot1 is inactive and are stabilized under blue light in a phot1-dependent manner. We propose that RPT2 is a molecular rheostat that maintains a moderate activation level of phot1 under any light intensity conditions.

The impact of worsening renal function with elevated B-type natriuretic peptide at discharge on 1-year prognosis in heart failure patients.

There are a few studies about the clinical impacts of plasma B-type natriuretic peptide (BNP) at discharge with the occurrence of worsening renal function (WRF) on mortality in patients with heart failure (HF). We divided total 301 patients with acute decompensated HF into four groups by the median value (278.7 pg/mL) of BNP level at discharge and by the occurrence of WRF. WRF developed in 100 patients (33.2%). Cardiovascular mortality was significantly different between the four groups (P = 0.0002). Patients with WRF and elevated BNP had a higher cardiovascular mortality than patients without WRF and elevated BNP in Cox proportional hazard models (hazard ratio [HR], 10.48; 95% confident interval [95% CI], 1.27-225.53; P = 0.03). Patients with either WRF or elevated BNP did not have an increased risk of cardiovascular mortality compared to patients without WRF and elevated BNP. Regarding HF readmission and cardiovascular mortality, patients with WRF and elevated BNP had the highest risk (HR, 5.17; 95% CI, 2.07-14.30, P = 0.0003) and patients with either WRF or elevated BNP had a higher risk than patients without WRF and elevated BNP. The occurrence of WRF combined with elevated BNP at discharge was associated with increased 1-year cardiovascular mortality and HF readmission.

Low-fluence blue light-induced phosphorylation of Zmphot1 mediates the first positive phototropism.

Phototropin1 (phot1) perceives low- to high-fluence blue light stimuli and mediates both the first and second positive phototropisms. High-fluence blue light is known to induce autophosphorylation of phot1, leading to the second positive phototropism. However, the phosphorylation status of phot1 by low-fluence blue light that induces the first positive phototropism had not been observed. Here, we conducted a phosphoproteomic analysis of maize coleoptiles to investigate the fluence-dependent phosphorylation status of Zmphot1. High-fluence blue light induced phosphorylation of Zmphot1 at several sites. Notably, low-fluence blue light significantly increased the phosphorylation level of Ser291 in Zmphot1. Furthermore, Ser291-phosphorylated and Ser369Ser376-diphosphorylated peptides were found to be more abundant in the low-fluence blue light-irradiated sides than in the shaded sides of coleoptiles. The roles of these phosphorylation events in phototropism were explored by heterologous expression of ZmPHOT1 in the Arabidopsis thaliana phot1phot2 mutant. The first positive phototropism was restored in wild-type ZmPHOT1-expressing plants; however, plants expressing S291A-ZmPHOT1 or S369AS376A-ZmPHOT1 showed significantly reduced complementation rates. All transgenic plants tested in this study exhibited a normal second positive phototropism. These findings provide the first indication that low-fluence blue light induces phosphorylation of Zmphot1 and that this induced phosphorylation is crucial for the first positive phototropism.

Physiological Characterization of Phototropism in Arabidopsis Seedlings.

To date, many mutants have been isolated from dicot plants, including Arabidopsis thaliana, and the physiological roles of the isolated genes have been identified. Molecular genetic analyses have usually been conducted in the model plant Arabidopsis to identify blue-light photoreceptors and key signaling components in phototropic responses. Despite these investigations, several molecular mechanisms involved in phototropism remain unknown, possibly because detailed physiological analyses have not been conducted properly in the isolated mutants. This chapter describes an approach for the detailed investigation of hypocotyl and root phototropism in Arabidopsis seedlings. The information provided here is expected to facilitate the analysis of phototropic responses in other plant species.

Serum zinc concentration in patients with acute myocardial infarction in percutaneous coronary intervention era.

INTRODUCTION: There were few studies that investigated the association between serum zinc concentration and acute myocardial infarction (AMI) in percutaneous coronary intervention era. OBJECTIVE: We assessed the relationships between serum zinc concentration, complications, and prognosis in AMI patients after primary percutaneous coronary intervention. METHODS: We conducted a single-center, prospective, observational study including 50 patients with AMI. We divided patients into two groups (High-zinc group and Low-zinc group) by median serum zinc concentration and compared two groups about clinical outcomes up to 1 year follow up. RESULTS: The mean age of patients was 66.2 ± 11.8 years old. Patients in the Low-zinc group had ST-segment elevation more frequently than those in the High-zinc group (96.0% vs. 72.0%, P = 0.02). All-cause mortality at 1 year was similar in both groups (P (log-rank) = 0.33). However, the lengths of hospital stay and in coronary care unit were longer in patients in the Low-zinc group than in those in the High-zinc group (15.6 ± 9.2 days vs. 11.9 ± 2.9 days, P = 0.06; 3.9 ± 2.8 days vs. 2.3 ± 0.8 days, P = 0.01). Multivariate regression analysis showed that low serum zinc concentration was associated with the use of cardiac or respiratory assist devices (adjusted odds ratio, 17.79; 95% CI 1.123 to 1216.5; P = 0.04). CONCLUSIONS: Although there was no significance difference in mortality in Low-zinc and High-zinc groups, low serum zinc concentration was associated with longer stay in the coronary care unit, and was one of the independent predictors for the use of cardiac or respiratory assist devices.

Roles of AGCVIII Kinases in the Hypocotyl Phototropism of Arabidopsis Seedlings.

Regulation of protein function by phosphorylation and dephosphorylation is an important mechanism in many cellular events. The phototropin blue-light photoreceptors, plant-specific AGCVIII kinases, are essential for phototropic responses. Members of the D6 PROTEIN KINASE (D6PK) family, representing a subfamily of the AGCVIII kinases, also contribute to phototropic responses, suggesting that possibly further AGCVIII kinases may potentially control phototropism. The present study investigates the functional roles of Arabidopsis (Arabidopsis thaliana) AGCVIII kinases in hypocotyl phototropism. We demonstrate that D6PK family kinases are not only required for the second but also for the first positive phototropism. In addition, we find that a previously uncharacterized AGCVIII protein, AGC1-12, is involved in the first positive phototropism and gravitropism. AGC1-12 phosphorylates serine residues in the cytoplasmic loop of PIN-FORMED 1 (PIN1) and shares phosphosite preferences with D6PK. Our work strongly suggests that the D6PK family and AGC1-12 are critical components for both hypocotyl phototropism and gravitropism, and that these kinases control tropic responses mainly through regulation of PIN-mediated auxin transport by protein phosphorylation.

Asymmetric Auxin Distribution is Not Required to Establish Root Phototropism in Arabidopsis.

An asymmetric auxin distribution pattern is assumed to underlie the tropic responses of seed plants. It is unclear, however, whether this pattern is required for root negative phototropism. We here demonstrate that asymmetric auxin distribution is not required to establish root phototropism in Arabidopsis. Our detailed analyses of auxin reporter genes indicate that auxin accumulates on the irradiated side of roots in response to an incidental gravitropic stimulus caused by phototropic bending. Further, an agravitropic mutant showed a suppression of this accumulation with an enhancement of the phototropic response. In this context, our pharmacological and genetic analyses revealed that both polar auxin transport and auxin biosynthesis are critical for the establishment of root gravitropism, but not for root phototropism, and that defects in these processes actually enhance phototropic responses in roots. The auxin response factor double mutant arf7 arf19 and the auxin receptor mutant tir1 showed a slight reduction in phototropic curvatures in roots, suggesting that the transcriptional regulation by some specific ARF proteins and their regulators is at least partly involved in root phototropism. However, the auxin antagonist PEO-IAA [α-(phenylethyl-2-one)-indole-3-acetic acid] suppressed root gravitropism and enhanced root phototropism, suggesting that the TIR1/AFB auxin receptors and ARF transcriptional factors play minor roles in root phototropism. Taken together, we conclude from our current data that the phototropic response in Arabidopsis roots is induced by an unknown mechanism that does not require asymmetric auxin distribution and that the Cholodny-Went hypothesis probably does not apply to root phototropism.

Structurally Well-Defined Anion-Exchange Membranes Containing Perfluoroalkyl and Ammonium-Functionalized Fluorenyl Groups.

Novel anion-conductive polymers containing perfluoroalkyl and ammonium-functionalized fluorene groups were synthesized and characterized. The quaternized polymers synthesized using a dimethylaminated fluorene monomer had a well-defined chemical structure in which each fluorenyl group was substituted with two ammonium groups at specific positions. The resulting polymers had a high molecular weight (M n = 8.9-13.8 kDa, M w = 13.7-24.5 kDa) to provide bendable thin membranes with the ion-exchange capacity (IEC) ranging from 0.7 to 1.9 mequiv g-1 by solution casting. Both transmission electron microscopy images and small-angle X-ray scattering patterns suggested that the polymer membranes possessed a nanoscale phase-separated morphology based on the hydrophilic/hydrophobic differences in the polymer components. Unlike typical anion-exchange membranes found in the literature, hydroxide ion conductivity of the membranes did not increase with increasing IEC because of their high swelling capability in water. The membrane with IEC = 1.2 mequiv g-1 showed balanced properties of high hydroxide ion conductivity (81 mS cm-1 at 80 °C in water) and mechanical strength (>100% elongation and 14 MPa maximum stress at 80 °C, 60% relative humidity). The polymer main chains were stable in 4 M KOH for 1000 h, whereas the trimethylbenzyl-type ammonium groups degraded under the conditions to cause loss in the hydroxide ion conductivity. An H2/O2 fuel cell with the membrane with IEC = 1.2 mequiv g-1 exhibited a maximum power density of 242 mW cm-2 at 580 mA cm-2 current density.

JNK activation is essential for activation of MEK/ERK signaling in IL-1ß-induced COX-2 expression in synovial fibroblasts.

The proinflammatory cytokine interleukin 1ß (IL-1ß) induces prostaglandin E2 (PGE2) production via upregulation of cyclooxygenase-2 (COX-2) expression in synovial fibroblasts. This effect of IL-1ß is involved in osteoarthritis. We investigated MAPK signaling pathways in IL-1ß-induced COX-2 expression in feline synovial fibroblasts. In the presence of MAPK inhibitors, IL-1ß-induced COX-2 expression and PGE2 release were both attenuated. IL-1ß induced the phosphorylation of p38, JNK, MEK, and ERK1/2. A JNK inhibitor prevented not only JNK phosphorylation but also MEK and ERK1/2 phosphorylation in IL-1ß-stimulated cells, but MEK and ERK1/2 inhibitors had no effect on JNK phosphorylation. A p38 inhibitor prevented p38 phosphorylation, but had no effect on MEK, ERK1/2, and JNK phosphorylation. MEK, ERK1/2, and JNK inhibitors had no effect on p38 phosphorylation. We also observed that in IL-1ß-treated cells, phosphorylated MEK, ERK1/2, and JNK were co-precipitated with anti-phospho-MEK, ERK1/2, and JNK antibodies. The silencing of JNK1 in siRNA-transfected fibroblasts prevented IL-1ß to induce phosphorylation of MEK and ERK1/2 and COX-2 mRNA expression. These observations suggest that JNK1 phosphorylation is necessary for the activation of the MEK/ERK1/2 pathway and the subsequent COX-2 expression for PGE2 release, and p38 independently contributes to the IL-1ß effect in synovial fibroblasts.