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Retinoblastoma is the most common malignant intraocular tumor in children. Y79 human retinoblastoma cells are in vitro models of retinal tumors used for drug screening. Undifferentiated Y79 cells originate from a primitive multi-potential neuroectodermal cell and express neuronal and glial properties. However, the nature of cellular heterogeneity in Y79 cells is unclear because functional methods to characterize neurons or glial cells have not been employed to Y79 cells. Here, we perform patch-clamp recordings to characterize electrophysiological properties in retinoblastoma cells. We identified a population of large-sized Y79 cells (i.e., giant cells, ~ 40-µm diameter), hyperpolarized resting membrane potential (–54 mV), and low input resistance (~ 600 MΩ), indicating electrically mature cells. We also found that giant Y79 cells contain increased density of T-type calcium channels. Finally, we found that T-type calcium channels are active only in giant cells suggesting that cancer treatments aimed to prevent calcium influx in retinoblastomas should be tested in giant cells.

Although most relationships are not symmetrical but interrelated, studies on the antecedents of customer attitude using SOR framework have focussed on the main effects and primacy issues of particu...

In a peer-to-peer (P2P) sharing-service model, a platform provider (PP) has no direct control over the service quality of peer service providers (PSPs). However, an unpleasant experience with a single PSP may impact customer responses to the PP. Hence, the PP should offer PSPs guidelines on how to cope with service failures. To identify effective/ineffective recovery strategies, this study examined the influence of the characteristics of service failure/recovery and customers that influence customers’ behavioral intentions toward the PP. Specifically, it employed multiple regression analysis (MRA) and fuzzy-set qualitative comparative analysis (fsQCA) to analyze the complex relationships between service failure/recovery characteristics (severity of service failure and source of service recovery) and customers’ characteristics (PSP experience, age, and gender) regarding customers’ behavioral intentions (reuse and switching intentions of the PP). The results show (1) four solutions leading to high reuse intention and two solutions leading to high switching intention of the PP when the severity of service failure is high and (2) three solutions leading to high reuse intention and two solutions leading to high switching intention of the PP when the severity of service failure is low. By investigating recovery configurations reflecting the unique characteristics of P2P sharing services, this study contributes to the literature on both P2P sharing services and service failure/recovery.

BACKGROUND Febrile urinary tract infection (fUTI) is a common bacterial infection among children. This study investigated the risk factors for febrile urinary tract infection (fUTI) caused by cefazolin-resistant bacteria in children. METHODS The medical records of patients with fUTI hospitalized between April 2014 and March 2020 were retrospectively analyzed. The patients were divided into two groups on the basis of the cefazolin susceptibility of the infection-causing bacteria: cefazolin-resistant and cefazolin-susceptible groups. RESULTS The records of 80 patients were evaluated. The median age was 5.0 (0.5-119.4) months. Cefazolin-susceptible bacteria were detected in 60 patients (75.0%). Significant differences were noted between the cefazolin-resistant and cefazolin-susceptible groups regarding UTI-related antimicrobial prophylaxis and recurrence of UTI within 3 months (p=0.0318 and p=0.00876, respectively). However, no significant differences were observed between these two groups regarding renal anomalies, UTI history. Logistic regression analysis revealed that the recurrence of UTI within 3 months was an independent significant risk factor for cefazolin-resistant fUTI (OR 3.81, 95% CI: 1.07-13.5, p=0.0388). Six patients who were empirically treated with antibiotics ineffective against the infection-causing bacteria recovered from fever before these antibiotics were switched to those effective against the infection-causing bacteria. CONCLUSIONS In children, a recurrence of UTI within 3 months is a risk factor for fUTI caused by cefazolin-resistant bacteria. Recognizing these risk factors before initiating fUTI treatment may support the treatment with narrower-spectrum antibiotics such as the first-generation cephalosporins (e.g., cefazolin) in children.

Retinoblastoma is the most common malignant intraocular tumor in children. Y79 human retinoblastoma cells are in vitro models of retinal tumors used for drug screening. Undifferentiated Y79 cells originate from a primitive multi-potential neuroectodermal cell and express neuronal and glial properties. However, the nature of cellular heterogeneity in Y79 cells is unclear because functional methods to characterize neurons or glial cells have not been employed to Y79 cells. Here, we perform patch-clamp recordings to characterize electrophysiological properties in retinoblastoma cells. We identified a population of large-sized Y79 cells (i.e., giant cells, ~ 40-µm diameter), hyperpolarized resting membrane potential (-54 mV), and low input resistance (~ 600 MΩ), indicating electrically mature cells. We also found that giant Y79 cells contain increased density of T-type calcium channels. Finally, we found that T-type calcium channels are active only in giant cells suggesting that cancer treatments aimed to prevent calcium influx in retinoblastomas should be tested in giant cells.

Timing and temporal precision of action potential generation are thought to be important for encoding of information in the brain. The ability of single neurons to transform their input into output action potential is primarily determined by intrinsic excitability. Particularly, plastic changes in intrinsic excitability represent the cellular substrate for spatial memory formation in CA1 pyramidal neurons (CA1-PNs). Here, we report that synaptically activated mGluR5-signaling can modulate the intrinsic excitability of CA1-PNs. Specifically, high-frequency stimulation at CA3-CA1 synapses increased firing rate and advanced spike onset with an improvement of temporal precision. These changes are mediated by mGluR5 activation that induces cADPR/RyR-dependent Ca2+ release in the dendrites of CA1-PNs, which in turn causes an increase in persistent Na+ currents (INa,P) in the dendrites. When group I mGluRs in CA1-PNs are globally activated pharmacologically, afterdepolarization (ADP) generation as well as increased firing rate are observed. These effects are abolished by inhibiting mGluR5/cADPR/RyR-dependent Ca2+ release. However, the increase in firing rate, but not the generation of ADP is affected by inhibiting INa,P. The differences between local and global activation of mGluR5-signaling in CA1-PNs indicates that mGluR5-dependent modulation of intrinsic excitability is highly compartmentalized and a variety of ion channels are recruited upon their differential subcellular localizations. As mGluR5 activation is induced by physiologically plausible brief high-frequency stimulation at CA3-CA1 synapses, our results suggest that mGluR5-induced enhancement of dendritic INa,P in CA1-PNs may provide important implications for our understanding about place field formation in the hippocampus.

Key points High-frequency stimulation (HFS) of the Schaffer collateral pathway activates metabotropic glutamate receptor 5 (mGluR5) signalling in the proximal apical dendrites of CA1 pyramidal neurons. The synaptic activation of mGluR5-mediated calcium signalling causes a significant increase in persistent sodium current (INa,P ) in the dendrites. Increased INa,P by HFS underlies potentiation of synaptic inputs at both the proximal and distal dendrite, leading to an enhanced probability of action potential firing associated with decreased action potential thresholds. Therefore, HFS-induced activation of intracellular mGluR5 serves an important role as an instructive signal for potentiation of upcoming inputs by increasing dendritic excitability. Abstract Dendritic Na+ channels in pyramidal neurons are known to amplify synaptic signals, thereby facilitating action potential (AP) generation. However, the mechanisms that modulate dendritic Na+ channels have remained largely uncharacterized. Here, we report a new form of short-term plasticity in which proximal excitatory synaptic inputs to hippocampal CA1 pyramidal neurons transiently elevate dendritic excitability. High-frequency stimulations (HFS) to the Schaffer collateral (SC) pathway activate mGluR5-dependent Ca2+ signalling in the apical dendrites, which, with calmodulin, upregulates specifically Nav1.6 channel-mediated persistent Na+ currents (INa,P ) in the dendrites. This HFS-induced increase in dendritic INa,P results in transient increases in the amplitude of excitatory postsynaptic potentials induced by both proximal SC and distal perforant path stimulation, leading to the enhanced probability of AP firing associated with decreased AP thresholds. Taken together, our study identifies dendritic INa,P as a novel target for mediating activity-dependent modulation of dendritic integration and neuronal output.

This research divides customers' on-site luxury shopping experiences into two stages—before and after entering a luxury shop—and then examines the effect of specific customer emotions in each stage. In detail, this study examines the impact of customer emotions before entering the store on their evaluations of in-store service quality, that of customer evaluations of each quality dimension on their in-store emotions, and that of in-store emotions on customer attitudes toward the brand. Further, this research tests the moderating effect of customers' personal attributes such as brand familiarity and shopping motive. Results demonstrate the importance of differentiating and managing customer emotions before and after entering a luxury shop and offer several insights into how to customize luxury customer service efforts to enhance customers' brand attitudes.

Repetitive action potentials (APs) in hippocampal CA3 pyramidal cells (CA3-PCs) backpropagate to distal apical dendrites, and induce calcium and protein tyrosine kinase (PTK)-dependent downregulation of Kv1.2, resulting in long-term potentiation of direct cortical inputs and intrinsic excitability (LTP-IE). When APs were elicited by direct somatic stimulation of CA3-PCs from rodents of either sex, only a narrow window of distal dendritic [Ca2+] allowed LTP-IE because of Ca2+-dependent coactivation of PTK and protein tyrosine phosphatase (PTP), which renders non-mossy fiber (MF) inputs incompetent in LTP-IE induction. High-frequency MF inputs, however, could induce LTP-IE at high dendritic [Ca2+] of the window. We show that MF input-induced Zn2+signaling inhibits postsynaptic PTP, and thus enables MF inputs to induce LTP-IE at a wide range of [Ca2+]ivalues. Extracellular chelation of Zn2+or genetic deletion of vesicular zinc transporter abrogated the privilege of MF inputs for LTP-IE induction. Moreover, the incompetence of somatic stimulation was rescued by the inhibition of PTP or a supplement of extracellular zinc, indicating that MF input-induced increase in dendritic [Zn2+] facilitates the induction of LTP-IE by inhibiting PTP. Consistently, high-frequency MF stimulation induced immediate and delayed elevations of [Zn2+] at proximal and distal dendrites, respectively. These results indicate that MF inputs are uniquely linked to the regulation of direct cortical inputs owing to synaptic Zn2+signaling.SIGNIFICANCE STATEMENTZn2+has been mostly implicated in pathological processes, and the physiological roles of synaptically released Zn2+in intracellular signaling are little known. We show here that Zn2+released from hippocampal mossy fiber (MF) terminals enters postsynaptic CA3 pyramidal cells, and plays a facilitating role in MF input-induced heterosynaptic potentiation of perforant path (PP) synaptic inputs through long-term potentiation of intrinsic excitability (LTP-IE). We show that the window of cytosolic [Ca2+] that induces LTP-IE is normally very narrow because of the Ca2+-dependent coactivation of antagonistic signaling pairs, whereby non-MF inputs become ineffective in inducing excitability change. The MF-induced Zn2+signaling, however, biases toward facilitating the induction of LTP-IE. The present study elucidates why MF inputs are more privileged for the regulation of PP synapses.

As firms’ interest in actively engaging customers throughout the business process grows, so has firms’ need to better understand its impact on service outcomes not only from the firm’s perspective but also from the customer’s perspective. This study is an attempt to define “customer's active role-play” in a service delivery system, identify its key dimensions and measurement items, and assess its impact on customers, particularly on customer perceptions of service outcomes as opposed to objective service outcomes.

Long-term potentiation (LTP) of synaptic responses is essential for hippocampal memory function. Perforant-path (PP) synapses on hippocampal granule cells (GCs) contribute to the formation of associative memories, which are considered the cellular correlates of memory engrams. However, the mechanisms of LTP at these synapses are not well understood. Due to sparse firing activity and the voltage attenuation in their dendrites, it remains unclear how associative LTP at distal synapses occurs. Here we show that NMDA receptor-dependent LTP can be induced at PP-GC synapses without backpropagating action potentials (bAPs) in acute rat brain slices. Dendritic recordings reveal substantial attenuation of bAPs as well as local dendritic Na + ‐spike generation during PP-GC input. Inhibition of Na+ ‐spikes impairs LTP suggesting that LTP at PP-GC synapse requires local Na + ‐spikes. Thus, dendritic spikes are essential for LTP induction at PP-GC synapse and may constitute a key cellular mechanism for memory formation in the dentate gyrus.

We report the development of a codominant sequence characterized amplified region (SCAR) marker linked to bacterial wilt resistance in tomato line Hawaii 7996. Bulked segregant analysis was employed for rapid identification of RAPD markers linked to resistance genes. Genomic DNA from six resistant F9 recombinant inbred lines (RILs) and six susceptible F9 RILs, which derived from a cross between S. lycopersicum Hawaii 7996 (resistant parent) and S. pimpinellifolium WVa 700 (susceptible parent) were pooled in to an R-pool and an S-pool, respectively. A total of 800 RAPD primers were screened and only six primers (UBC#176, 205, 287, 317, 350, and 676) showed polymorphism between R- and S- pools. Of these, only two markers UBC#176 and 317 revealed a 100% linkage in the individual plants comprising the contrasting bulks. Of these, the marker UBC#176 was converted into a codominant SCAR marker and designated as SCU176-534. The marker SCU176-534 was confirmed by genotyping the individual of the R- and S- pools and gave the same result as UBC#176. When the marker SCU176-534 was further validated for association with resistance and its potential for maker-assisted selection (MAS) in 92 tomato lines and cultivars, the results showed that none of these carries the resistance gene. Thus, SCAR marker SCU176-534 can be used in early selection of resistant lines when Hawaii 7996 is used as a parent in a breeding program.

Key points We investigated the cellular mechanisms underlying mossy fibre-induced heterosynaptic long-term potentiation of perforant path (PP) inputs to CA3 pyramidal cells. Here we show that this heterosynaptic potentiation is mediated by downregulation of Kv1.2 channels. The downregulation of Kv1.2 preferentially enhanced PP-evoked EPSPs which occur at distal apical dendrites. Such enhancement of PP-EPSPs required activation of dendritic Na+ channels, and its threshold was lowered by downregulation of Kv1.2. Our results may provide new insights into the long-standing question of how mossy fibre inputs constrain the CA3 network to sparsely represent direct cortical inputs. Abstract A short high frequency stimulation of mossy fibres (MFs) induces long-term potentiation (LTP) of direct cortical or perforant path (PP) synaptic inputs in hippocampal CA3 pyramidal cells (CA3-PCs). However, the cellular mechanism underlying this heterosynaptic modulation remains elusive. Previously, we reported that repetitive somatic firing at 10 Hz downregulates Kv1.2 in the CA3-PCs. Here, we show that MF inputs induce similar somatic firing and downregulation of Kv1.2 in the CA3-PCs. The effect of Kv1.2 downregulation was specific to PP synaptic inputs that arrive at distal apical dendrites. We found that the somatodendritic expression of Kv1.2 is polarized to distal apical dendrites. Compartmental simulations based on this finding suggested that passive normalization of synaptic inputs and polarized distributions of dendritic ionic channels may facilitate the activation of dendritic Na+ channels preferentially at distal apical dendrites. Indeed, partial block of dendritic Na+ channels using 10 nm tetrodotoxin brought back the enhanced PP-evoked excitatory postsynaptic potentials (PP-EPSPs) to the baseline level. These results indicate that activity-dependent downregulation of Kv1.2 in CA3-PCs mediates MF-induced heterosynaptic LTP of PP-EPSPs by facilitating activation of Na+ channels at distal apical dendrites.

Introduction The purpose of this study was to investigate the effects of an isthmus on the success rate of surgically treated molars. Methods The study included 106 maxillary and mandibular first molars with endodontic lesions limited to the periapical area. Endodontic microsurgical procedures were performed according to the Yonsei protocol reported in a previous study. When an isthmus was observed after a high-magnification inspection, it was included in the retrograde preparation design. When an isthmus was not observed, only the main root canal space was prepared. The patients were followed up periodically every year after treatment. Success was defined as the absence of clinical signs and symptoms and radiographic evidence of complete or incomplete healing. Results Of the 106 teeth included in the study, 72 teeth had an isthmus, and 34 did not. Kaplan-Meier analysis revealed that the cumulative survival rate after surgery was 61.5% and 87.4% for 4 years when an isthmus was present and absent, respectively. A multivariate Cox proportional hazards regression analysis showed that the adjusted hazard ratio for failure was 6.01 times higher for the isthmus-present teeth than for the isthmus-absent teeth ( P Conclusions In this study, the success rate for endodontic microsurgery on isthmus-absent teeth was higher than that for isthmus-present teeth. Considering the success rate and potential risk of weakening the root after preparation, the techniques of isthmus preparation need to be improved.

In services in general, customers play critical roles in determining the success of service delivery. Some services (such as education) require an active participation of customers for the successful accomplishment of purchase objectives. Yet, there are few systematic and integrated researches in defining the dimensions of customer’s active participation and in empirically testing the effect of customer’s active participation on customer’s perceived performance (as opposed to the firm’ performance and customer satisfaction). Existing studies have focused mainly on the general concept of customer participation during a service encounter, leaving the specific concept of customer’s active participation in various situations still under-researched. Through this study, we intended to fill this gap in research. Specifically, using college business education as our study context, we first propose the concept of “customer’s active participation (CAP)” as the reflection of customer engagement concept and identify the dimensions of CAP. We then empirically examine the effect of CAP on customer perceptions of performance of their own (CPP). Through the review of literature on the topics of customer participation, customer engagement, employee engagement and focus group interviews, we defined customer’s active participation and identified its dimension as follows. We defined customer’s active participation as “customers' making not only their individual efforts to ensure the successful outcome of the service delivery but also active interacting with service providers, other customers, and others in and outside of the service delivery context to achieve their consumption goal”. We then identified five dimensions of customer’s active participation; in-service-space interaction, 3 kinds of outside-service-space interactions (customer-to-service provider, customer-to-customer, customer-to-others), and individual level participation both in and outside the service space. In order to collect necessary data, we administered a self-administered survey using a questionnaire among undergraduate-level business major students at Yonsei School of Business. As a result of an EFA, we confirmed the uni-dimensionality of each of five determinants and the reliability of the measurement items for each dimension. The CFA result of a different set of data collected from another set of respondents among undergraduate business major students at Yonsei School of Business, we confirmed that the five dimensions well explain the customer’s active participation (CAP). Results also supported that customer’s active participation (CAP) positively influences customer’s perceptions of performance (CPP). This study contributes academically and practically in several ways. First, this study is the first attempt to propose the concept of “customer’s active participation (CAP)”. Second, this study identified the major determinants of CAP and developed a scale in the business education context. Third, this study empirically verified and the importance of the effect of CAP on their perception of own performance. Practically, this study contributes by showing the importance of managing CAP and by proposing the specific dimensions of CAP that should be managed.

CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic domains. In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na(+) channel-mediated dendritic spikes are efficiently initiated by waveforms mimicking synaptic events. CA3 pyramidal neuron dendrites showed a high Na(+)-to-K(+) conductance density ratio, providing ideal conditions for active backpropagation and dendritic spike initiation. Dendritic spikes may enhance the computational power of CA3 pyramidal neurons in the hippocampal network.