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We evaluate the overall effectiveness of the nationwide vaccination campaign using ChAdOx1 nCoV-19, BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines in preventing Covid-19 in South Korea.The National Surveillance System with the National Immunization Registry were linked to form a large-linked database for assessment. Age-adjusted incidence of SARS-CoV-2 infection, severe disease, and death by vaccination status are calculated. Weekly vaccine effectiveness was calculated based on incidence rate ratio (IRR) between fully-vaccinated and unvaccinated persons, as: IRR = incidence rate of vaccinated / incidence rate of unvaccinated. We estimate the cumulative SARS-CoV-2 outcome overtime comparing the observed case with predicted cases without vaccination.Age-adjusted incidence in unvaccinated persons (5.69 per 100,000 person-day) was 2.7 times the rate in fully vaccinated (2.13 per 100,000 person-day) persons, resulting effectiveness against SARS-CoV-2 infection of 63%. Vaccine effectiveness against severe disease and death were 93% and 95%, respectively. Between March and October 2021, estimated Covid-19 related outcomes averted by vaccinations were: 46,508 infections, 3,424 severe diseases, and 718 deaths.We found significant protection for national Covid-19 vaccination campaign against Covid-19 severe disease, and death in target populations, but there was an unexpected decreased protection against SARS-CoV-2 infection, highlighting the importance of continued surveillance and assessment.

Wires in field applications, such as aircraft, are often exposed to stress conditions, including overheating, moisture ingress, or inherent defects, which may result in electrical discontinuity, wire insulation breakdown, and system failure. This study proposed a nondestructive and real-time wire fault diagnosis method through resistance spectroscopy to diagnose the health of wires under stress conditions. Wire abrasion tests were conducted by applying cyclic mechanical stress to produce gradual damage to a wire under test. During abrasion testing, a lock-in amplifier generated high-frequency signals and monitored the signals transmitted through the wire to diagnose the wire failure under test. Differences in signal amplitude, and phase shift spectra during wire degradation exhibited specific and distinguishable behavior based on the physical damage progression of the tested wire. Test results implied that resistance spectroscopy analysis could serve as a nondestructive wire fault diagnosis method, providing damage progression in real time.

Objective: This study aimed to ascertain what should be considered in the "Guideline for Clinical Trials with Herbal Medicinal Products for Liver Cancer," by analyzing existing guidelines and clinical trials. Methods: Committee for the development of a guideline, consisting of 6 Korean medicine doctors, reviewed guidelines and clinical trials on using herbal medicine for treating liver cancer. The trials were analyzed in terms of inclusion and exclusion of participants, intervention, comparators, outcomes, and trial design. We then compared the results of our analysis with the guidelines to identify issues we must to consider when following the "Guideline for Clinical Trials with Herbal Medicinal Products for Liver Cancer." Several guidelines for antitumor agents and clinical trials on herbal medicine were obtained from the Ministry of Food and Drug Safety homepage, etc. The search terms were as follows: "liver neoplasms"; "herbal medicine"; "medicine, Korean traditional"; and "medicine, Chinese Traditional.". Results: Ten articles were obtained from pubmed and Embase. There was no guideline for clinical trials on using herbal medicine for treating liver cancer. All the participants in the reviewed articles had primary liver cancer, and the type of intervention varied (e.g., decoction, patches, and capsules. The comparators included placebos and conventional treatments such as chemotherapy. The outcome assessment methods were tumor response, quality of life, survival, and liver function tests. Adverse events occuring during the trial were also evaluated. Conclusion: Findings were derived by reviewing existing guidelines and comparing them with clinical trials on liver cancer and herbal medicinal products. These results will be utilized in the development of the "Guideline for Clinical Trials with Herbal Medicinal Products for Liver Cancer."

The 2015 revised national English curriculum emphasizes developing English communicative competence. This study investigates effective teaching...

Streptococcus mutans (S. mutans), a major aetiologic agent of dental caries, is involved in systemic diseases, such as bacterial endocarditis, if it enters the bloodstream through temporary bacteraemia. Interleukin (IL)-1β, a proinflammatory cytokine, is related to the host defences against pathogens, and its synthesis, maturation, and secretion are tightly regulated by the activation of the inflammasome, an inflammatory signalling complex. This study examined the signalling mechanism of IL-1β secretion and the inflammasome pathway induced by S. mutans to explain the molecular mechanism through which systemic infection by oral streptococci can occur. After infection of THP-1 cells with S. mutans, the expression of inflammasome components was detected using various methods. S. mutans induced IL-1β secretion via caspase-1 activation, and S. mutans-induced IL-1β secretion required absent in melanoma (AIM2), NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing 4 (NLRC4) inflammasome activation. In particular, the S. mutans-induced NLRP3 inflammasome was mediated by adenosine triphosphate (ATP) release, potassium depletion and lysosomal damage. Our study provides novel insight into the innate immune response against S. mutans infection., Bacterial infection: The immune response to Streptococcus mutans Streptococcus mutans triggers an early-stage immune response via a chain of events that leads to the activation of immune component, interleukin-1β. A group of academics from Korea’s Pusan National University, led by Jin Chung, tested the response of human immune cell cultures to infection with S. mutans—a common oral bacteria that can cause systemic disease if it enters the bloodstream. The group found that S. mutans infection leads to the activation of protein signaling complexes known as inflammasomes, which in turn activate an enzyme known as caspase-1. Caspase-1 then activates interleukin-1β, a pro-inflammatory molecule that forms part of a host’s defenses against pathogens. The team also identified that ATP release, ion depletion, and integrity of intracellular enzyme containers, also impacted inflammasome activation. This study offers insights into the immune response against S. mutans and may inform future investigations into systematic oral bacteria infections.

Summary This study evaluated the bacterial leakage resistance and root canal lining efficacy of various root canal filling materials and methods by using confocal laser-scanning microscope (CLSM). Sixty extracted human premolars with mature apex and single root canal were randomly divided into 2 control groups and 4 experimental groups. Group CW was filled with continuous wave technique using gutta-percha and AH Plus sealer. Group GC was coated with AH-Plus sealer and then obturated with soften GuttaCore. Group GF was obturated using GuttaFlow and gutta-percha. Group EM was filled with EndoSeal MTA and gutta-percha using ultrasonic vibration. The AH-Plus, GuttaFlow, and EndoSeal were labeled with Hoechst 33342 to facilitate fluorescence. The obturated root tip was incubated with Carboxyfluorescein diacetate succinimidyl ester (CFSE)-stained E. faecalis for 14 days. CLSM was performed to evaluate the sealer distribution and bacterial leakage for the apical 1-, 2-, 3-mm specimens. Statistically significant differences were determined by 1-way ANOVA with Tukey's post-hoc test and Pearson's correlation analysis. Group EM showed the better sealer distribution score than the other groups (p 0.05). Under the conditions of this study, different root canal filling materials and methods showed different efficacy for canal distribution and bacterial leakage resistance. SCANNING 37:422–428, 2015. © 2015 Wiley Periodicals, Inc.

It has been clarified that chromium deposition occurs significantly onthe electrolyte surface near the cathode reaction sites in consequence of cathode polarization. The deposited chromium probably remains on the surface, not diffusing into the electrolyte. Therefore, focusing on the behavior of the deposited chromium, such as crystal growth or dissipation by cathode polarization change is suitable for clarification of the deposition mechanism in detail. In this study, we investigated influence of cathode polarization change on the deposited chromium on the electrolyte surface by using NiO/YSZ or NiO/GDC for the cathode material. We used NiO for the cathode material because of the following two reasons. 1) Effect of cathode polarization can easily be studied because the predetermined cathode polarization is generated at the cathode reaction sites with smaller current flow. 2) Lower reactivity of NiO with chromium vapor than conventional cathode materials (e.g. LSCF, LSM) can make the analysis simpler. Although ohmic resistances of these cathodes using NiO are higher than usual, they showed enough performance to control cathode polarization. Chromium poisoning tests were conducted at 700 oC for 100 hours keeping cathode polarization constant at 200 mV. At the end of the chromium poisoning tests, several different procedures to stop the cell tests were executed concerning the timing to remove the cathode polarization After the chromium poisoning tests at 200 mV, chromium deposition was observed on the surface of the electrolyte near the cathode/electrolyte interface as observed in LSM cathode. The deposited chromium segregated at the interface of NiO and YSZ for the NiO/YSZ cathode by decreasing cathode polarization, which suggests nucleation under cathode polarization at 200 mV and growth of chromium compounds after decreasing the cathode polarization. On the other hand, the deposited chromium decreased for the NiO/GDC cathode after decreasing cathode polarization.

Xylitol is a widely used anti-caries agent that has anti-inflammatory effects. We have evaluated the potential of xylitol in cancer treatment. It's effects on cell proliferation and cytotoxicity were measured by MTT assay and LDH assay. Cell morphology and autophagy were examined by immunostaining and immunoblotting. Xylitol inhibited cell proliferation in a dose-dependent manner in these cancer cells: A549, Caki, NCI-H23, HCT-15, HL-60, K562, and SK MEL-2. The IC50 of xylitol in human gingival fibroblast cells was higher than in cancer cells, indicating that it is more specific for cancer cells. Moreover, xylitol induced autophagy in A549 cells that was inhibited by 3-methyladenine, an autophagy inhibitor. These results indicate that xylitol has potential in therapy against lung cancer by inhibiting cell proliferation and inducing autophagy of A549 cells.

Chromium poisoning phenomena of solid oxide fuel cells (SOFCs) were investigated using (La 0.8 Sr 0.2 ) 0.98 MnO 3 (LSM), Pr 0.8 Sr 0.2 MnO 3 (PrSM), Nd 0.8 Sr 0.2 MnO 3 (NdSM), and Br 0.5 Sr 0.5 Co 0.8 Fe 0.2 O 3 (BSCF) for the cathode materials and yttria-stabilized zirconia (YSZ) as the electrolyte material at 700 °C under constant cathode polarization conditions. Deposition of chromium increased with increasing cathode polarization similarly for the four cathodes, although position of the deposition was different for the BSCF cathode. Chromium deposited near the cathode/electrolyte interface for the LSM cathode, the PrSM cathode and the NdSM cathode. Chromium deposition on the surface of the zirconia electrolyte was observed for the PrSM cathode and the NdSM cathode as previously observed in the LSM cathode. Oxygen deficiency in the deposited chromium on the surface of the zirconia electrolyte was also observed, thus the reaction mechanism of chromium vapor with the oxygen vacancy induced by cathode polarization was supported. The oxygen vacancy on the surface of the zirconia electrolyte seemed to be generated via metal oxides such as manganese oxide or neodymium oxide segregated from the cathode materials. Chromium deposited on the surface of the BSCF cathode. Cathode polarization seems to increase reactivity of BSCF and enhance trapping of chromium vapor near the cathode surface.

Xylitol is a well-known anticaries agent and has been used for the prevention and treatment of dental caries. In this study, the anti-inflammatory effects of xylitol are evaluated for possible use in the prevention and treatment of periodontal infections.Cytokine expression was stimulated in THP-1 (human monocyte cell line)-derived macrophages by live Porphyromonas gingivalis, and enzyme-linked immunosorbent assay and a commercial multiplex assay kit were used to determine the effects of xylitol on live P. gingivalis-induced production of cytokine. The effects of xylitol on phagocytosis and the production of nitric oxide were determined using phagocytosis assay, viable cell count, and Griess reagent. The effects of xylitol on P. gingivalis adhesion were determined by immunostaining, and costimulatory molecule expression was examined by flow cytometry.Live P. gingivalis infection increased the production of representative proinflammatory cytokines, such as tumor necrosis factor-α and interleukin (IL)-1β, in a multiplicity of infection- and time-dependent manner. Live P. gingivalis also enhanced the release of cytokines and chemokines, such as IL-12 p40, eotaxin, interferon γ-induced protein 10, monocyte chemotactic protein-1, and macrophage inflammatory protein-1. The pretreatment of xylitol significantly inhibited the P. gingivalis-induced cytokines production and nitric oxide production. In addition, xylitol inhibited the attachment of live P. gingivalis on THP-1-derived macrophages. Furthermore, xylitol exerted antiphagocytic activity against both Escherichia coli and P. gingivalis.These findings suggest that xylitol acts as an anti-inflammatory agent in THP-1-derived macrophages infected with live P. gingivalis, which supports its use in periodontitis.

Chromium poisoning phenomena were compared among three SOFC cathodes using (La0.8Sr0.2)0.98MnO3 (LSM), La0.6Sr0.4Fe0.8Co0.2O3 (LSCF) and LaNi0.6Fe0.4O3 (LNF) at 700 °C by changing cathode polarization (0–400 mV). Chromium vapor deposited near the electrolyte for LSM and LNF, and the amount of the deposition increased with increasing cathode polarization. In the case of LSCF, chromium deposited near the cathode surface under smaller cathode polarization (≤200 mV). Under larger cathode polarization (≥300 mV), however, chromium deposition near the cathode/electrolyte interface similarly increased for the three cathodes. Cathode polarization facilitated the chromium deposition and there seemed to be no correlation with the current density. Microscopic distribution of the deposited chromium, which was located on the surface of LSM, LSCF, LNF grains, and also on the surface of zirconia and ceria, seemed to correspond to the distribution of oxygen vacancy by cathode polarization at the electrode reaction sites. Chromium deposition on the zirconia surface seemed to be assisted by metal oxides segregated from the cathode material, which can conduct electron required for generating oxygen vacancy continuously. Oxygen deficiency on the surface of the deposited chromium was confirmed and interdiffusion of chromium and zirconium caused by cathode polarization was also suggested.

Metal supported cells with porous metallic substrates made of stainless steels are expected to drastically improve remaining issues of durability and cost for solid oxide fuel cells (SOFCs). In this study, we succeeded in fabricating a porous alloy substrate for SOFC using a Fe-Cr-Al type stainless steel, which showed excellent heat resistance. We investigated the application of the alloy substrate for the cathode side and good heat resistance and relatively low contact resistance between the alloy substrate and La0.6Sr0.4Co0.2Fe0.8O3 (LSCF) was obtained at 700oC in air.

Chromium poisoning phenomena were compared among three SOFC cathodes consisting of La0.8Sr0.2MnO3 (LSM), La0.6Sr0.4Fe0.8Co0.2O3 (LSCF) and LaNi0.6Fe0.4O3 (LNF) under relatively large cathode polarization conditions. Deposition of chromium near the cathode/electrolyte interface seems to be affected only by the cathode polarization, not by the cathode materials nor the current density.

Background Periodontitis is a chronic inflammatory disease induced by periodontopathogens such as Porphyromonas gingivalis (P. gingivalis). MicroRNAs (miRNAs) are small single-stranded noncoding RNAs that regulate gene expression at the level of translation. MiRNAs have been reported to be involved in inflammatory processes. In this study, we examined the effects of P. gingivalis-induced inflammatory miRNAs expression on TNFα production in THP-1 derived macrophages. Results Porphyromonas gingivalis induced the expression of miR-132. P. gingivalis-induced miR-132 expression was significantly inhibited by TLR2/4 knock-down and NF-κB inhibitor. Additionally, miR-132 antagomir strongly repressed production of TNFα. The expression of NFE2L2 and NFAT5, the putative target genes of miR-132 involved in regulation of TNFα, decreased in response to P. gingivalis. Furthermore, miR-132 antagomir rescued P. gingivalis-induced suppression of NFE2L2 and NFAT5. Conclusions These results suggest that the induction of miR-132 by P. gingivalis can modulate the pathogenesis of periodontitis induced via regulatory expression of TNFα.

We show that Rap2, a member of the Ras GTPase family, positively regulates Activin/Nodal signaling activity by controlling the trafficking of its receptors. In the absence of ligand activation, Rap2 directs internalized Activin/Nodal receptors into a recycling pathway, thereby preventing their degradation and maintaining their levels on the cell surface. Upon ligand activation, Rap2 no longer promotes receptor recycling but delays its turnover. In both cases, Rap2 contributes to upregulation of signaling activity by antagonizing Smad7. In addition, we found that the efficiency of Activin/Nodal receptor recycling is different between dorsal and ventral halves of Xenopus early embryo, which results from the asymmetric expression of Rap2 and Smad7. Consequently, they regulate cell responsiveness to ligands and the spatiotemporally dynamic activation of Smad2 along the dorsoventral axis of the embryo. Therefore, these findings suggest a molecular basis for the regulation of signaling activity and embryonic patterning by Activin/Nodal receptor trafficking.

Activin/Nodal signaling is essential for germ-layer formation and axial patterning during embryogenesis. Recent evidence has demonstrated that the intra- or extracellular inhibition of this signaling is crucial for ectoderm specification and correct positioning of mesoderm and endoderm. Here, we analyzed the function of Xenopus serum response factor (XSRF) in establishing germ layers during early development. XSRF transcripts are restricted to the animal pole ectoderm in Xenopus early embryos. Ectopic expression of XSRF RNA suppresses mesoderm induction, both in the marginal zone in vivo and caused by Activin/Nodal signals in animal caps. Dominant-negative mutant or antisense morpholino oligonucleotide-mediated inhibition of XSRF function expands the expression of mesendodermal genes toward the ectodermal territory and enhances the inducing activity of the Activin signal. SRF interacts with Smad2 and FAST-1, and inhibits the formation of the Smad2-FAST-1 complex induced by Activin. These results suggest that XSRF might act to ensure proper mesoderm induction in the appropriate region by inhibiting the mesoderm-inducing signals during early embryogenesis.

This study evaluated the bacterial leakage resistance and root canal lining efficacy of various root canal filling materials and methods by using confocal laser-scanning microscope (CLSM). Sixty extracted human premolars with mature apex and single root canal were randomly divided into 2 control groups and 4 experimental groups. Group CW was filled with continuous wave technique using gutta-percha and AH Plus sealer. Group GC was coated with AH-Plus sealer and then obturated with soften GuttaCore. Group GF was obturated using GuttaFlow and gutta-percha. Group EM was filled with EndoSeal MTA and gutta-percha using ultrasonic vibration. The AH-Plus, GuttaFlow, and EndoSeal were labeled with Hoechst 33342 to facilitate fluorescence. The obturated root tip was incubated with Carboxyfluorescein diacetate succinimidyl ester (CFSE)-stained E. faecalis for 14 days. CLSM was performed to evaluate the sealer distribution and bacterial leakage for the apical 1-, 2-, 3-mm specimens. Statistically significant differences were determined by 1-way ANOVA with Tukey's post-hoc test and Pearson's correlation analysis. Group EM showed the better sealer distribution score than the other groups (p 0.05). Group CW and group GC exhibited the less bacterial leakage than the group GF, while group EM showed the similar bacterial leakage score with the groups CW and GC. There was no significant correlation between the sealer distribution and bacterial leakage (p 0.05). Under the conditions of this study, different root canal filling materials and methods showed different efficacy for canal distribution and bacterial leakage resistance.

Recently in the R&D area DRAM has shrunk to 1X nm, at the same time patterning technology has been one of the major challenges on 1X nm DRAM. Less than 20nm line and space and less than 30nm contact hole patterning are basically needed for 1X nm DRAM. Currently ArF immersion extension such as DPT (Double Patterning Technology), SADP (Self-Aligned Double Patterning) and SAQP (Self-Aligned Quadruple Patterning) shows robust patterning performance relative to EUV/DSA and become established process as a baseline for 1Xnm DRAM. But cost of ownership and process complexity of DPT/SADP can be the big burden for volume production. Furthermore too many DPT/SADP can make DRAM shrink meaningless. In spite of current issues on DPT/SADP, EUV source power has been the most critical issue so far. And now source power issue is pushing development of high sensitive EUV resist and related process. In this paper, author will compare EUV PTD and NTD in view of image contrast and swelling, also evaluate patterning performance between EUV PTD and NTD, and finally describe current status and issues of EUV NTD.

Porphyromonas gingivalis , a major periodontopathogen, is involved in the pathogenesis of periodontitis. Interleukin-1β (IL-1β), a proinflammatory cytokine, regulates innate immune responses and is critical for the host defense against bacterial infection. However, excessive IL-1β is linked to periodontal destruction. IL-1β synthesis, maturation, and secretion are tightly regulated by Toll-like receptor (TLR) signaling and inflammasome activation. We found much higher levels of inflammasome components in the gingival tissues from patients with chronic periodontitis than in those from healthy controls. To investigate the molecular mechanisms by which P. gingivalis infection causes IL-1β secretion, we examined the characteristics of P. gingivalis -induced signaling in differentiated THP-1 cells. We found that P. gingivalis induces IL-1β secretion and inflammatory cell death via caspase-1 activation. We also found that P. gingivalis -induced IL-1β secretion and pyroptic cell death required both NLRP3 and AIM2 inflammasome activation. The activation of the NLRP3 inflammasome was mediated by ATP release, the P2X 7 receptor, and lysosomal damage. In addition, we found that the priming signal via TLR2 and TLR4 activation precedes P. gingivalis -induced IL-1β release. Our study provides novel insight into the innate immune response against P. gingivalis infection which could potentially be used for the prevention and therapy of periodontitis.

The aim of this study was to evaluate the physical properties and cytotoxicity of a novel root-end filling material (EPC) which is made from epoxy resin and Portland cement as a mineral trioxide aggregate (MTA) substitute. EPC, developed as a root-end filling material, was compared with MTA and a mixture of AH Plus sealer and MTA (AMTA) with regard to the setting time, radio-opacity, and microleakage. Setting times were evaluated using Vicat apparatus. Digital radiographs were taken to evaluate the aluminium equivalent radio-opacity using an aluminium step wedge. Extracted single-rooted teeth were used for leakage test using methylene blue dye. After canal shaping and obturation, the apical 3-mm root was resected, and a root-end cavity with a depth of 3 mm was prepared. The root-end cavities were filled with MTA, AMTA, and EPC for 15 specimens in each of three groups. After setting in humid conditions for 24 h, the specimens were tested for apical leakage. For evaluation of the biocompatibility of EPC, cell (human gingival fibroblast) viability was compared for MTA and Portland cement by MTT assay, and cell morphological changes were compared for MTA and AH Plus by fluorescence microscopy using DAPI and F-actin staining. The setting time, radio-opacity, and microleakage were compared using one-way ANOVA and Scheffe’s post hoc comparison, and the cytotoxicity was compared using the nonparametric Kruskal–Wallis rank sum test. Statistical significance was set at 95 %. EPC had a shorter setting time and less microleakage compared with MTA (p

A method is presented for the modelling and animation of generalized cylinders with variable radius offset space curves. The boundary surface of a generalized cylinder is constructed: either as a translational sweep of cross-sectional curves along the skeleton curve, or as a rotational sweep of profile curves around the skeleton curve. The cross-sectional curves are computed as the variable radius offset curves of a circle in the normal plane, and the profile curves are computed as the variable radius offset space curves of the skeleton curve. The offset curves are approximated by spline curves, and the boundary surface of a generalized cylinder is approximated by the tensor product surface patches of the offset spline curves.

The quadratic inference function (QIF) is a new statistical methodology developed for the estimation and inference in longitudinal data analysis using marginal models. This method is an alternative to the popular generalized estimating equations approach, and it has several useful properties such as robustness, a goodness-of-fit test and model selection. This paper presents an introductory review of the QIF, with a strong emphasis on its applications. In particular, a recently developed SAS MACRO QIF is illustrated in this paper to obtain numerical results.

This reference is for an abstract only. A full paper was not submitted for this conference. Abstract Basements rarely form hydrocarbon reservoirs; and consequently are rarely considered as hydrocarbon exploration targets. The few basement reservoirs are classified as unconventional reservoirs. In addition to the usual uncertainties in hydrocarbon exploration, three additional components are necessary for the success in basement reservoir exploration; Time lag between the peak time of hydrocarbon generation and tectonic movement that create fracture systems in the basement,contact area between source rocks and basement surface andlimited migration paths. In the Sabatayn basin, Yemen, the Jurassic Kimmeridgian Madbi shale is the source rock and regional evaporites seal the entrapped hydrocarbons. The shale expelled the hydrocarbons during early Cretaceous into previously fractured Pre-Cambrian basement. Integrated interpretation of gravity and 2D seismic data defined the poorly imaged basement highs in the basin. This work provided a cost-effective evaluation method for identifying basement highs forming the hydrocarbon reservoirs.

POSH (plenty of SH3s) acts as a scaffold that links activated Rac1 and downstream c-Jun N-terminal kinase (JNK) signaling modules. However, it is unknown whether it's functional domain-mediated roles including the interesting RING-finger domain or its cellular function. Here, we provide evidence that subcellular localization of POSH is regulated by a particular domain of the protein and POSH was colocalized with hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) on early endosomes via interaction of Hrs with POSH's two rear SH3 domains. Moreover, the RING domain of POSH specifically regulates the stability of Hrs, but not of JNK1, via a ubiquitin-proteasomal degradation pathway. Finally, we demonstrate that JNK1 does not interact with Hrs under the conditions of POSH interacted with Hrs, but instead reduces the POSH-catalyzed ubiquitination of Hrs and their reciprocal interaction. Together, these data suggest that POSH has a distinct role as a specific E3 ubiquitin ligase for Hrs on early endosomes, and there exists a relationship between its separate activities as a scaffold and as an E3.

Convergent extension (CE) movements in gastrulation are essential for the establishment of the body axis during early vertebrate development. Although the precise molecular mechanisms of CE movements are not clearly understood, noncanonical Wnt pathway is known to be important for the control of CE movements. Here, we present evidence that PKA is implicated in noncanonical Wnt pathway. Overexpression and specific depletion of PKA inhibit CE movements. PKA depletion also disrupts cell morphology, protrusive activity, and cortical actin formation in dorsal mesodermal cells. Moreover, PKA activity is negatively regulated by major components of planar cell polarity (PCP) pathway. In line with this, overexpression of PKA can rescue the inhibition of CE movements caused by overexpression of these molecules. We also demonstrate that this regulation of PKA activity is dependent upon Gαi signaling. As a negative component of PCP signaling, PKA inhibits not only the activation of RhoA and JNK but also the Dsh-Daam1-RhoA complex formation which is essential for the regulation of RhoA activity. Together, our study suggests a molecular pathway from Wnt/Dsh/PKA signaling to Rho activation in PCP signaling.

POSH (Plenty of SH3s) has distinct roles as a scaffold for specific c-Jun N-terminal kinase (JNK) signaling modules and as an E3 ubiquitin ligase. The physiological function of POSH remains unclear, however, and its possible involvement in developmental processes motivated the present study wherein the Xenopus orthologue of POSH (xPOSH) was examined for its potential role during Xenopus early embryogenesis. Loss-of-function analysis using morpholino oligonucleotides demonstrated that POSH was essential for Xenopus anterior neural development, although not Spemann organizer formation and early neurogenesis, through the formation of an active JNK signaling complex. Moreover, POSH-mediated JNK pathway was essential for apoptosis in anterior neural tissues. Finally, the present findings demonstrate that RING (Really Interesting New Gene) domain-mediated E3 ubiquitin ligase activity of POSH was not involved in POSH-mediated JNK pathway in vivo. Together, these data suggest that the active JNK signaling complex formed of POSH and the JNK module is essential for the expression of anterior neural genes and apoptosis in Xenopus anterior development.

not Available.