Progesterone Receptor Agonist, Nestorone, Exerts Long-Term Neuroprotective Effects Against Permanent Focal Cerebral Ischemia in Adult and Aged Male Rats.

Stroke is a leading cause of death and disability worldwide. Tissue plasminogen activator (tPA) is currently the most effective medicine for stroke; however, it has a narrow therapeutic time window (4.5 h after symptom onset). We demonstrated that nestorone, a progesterone (P4) receptor agonist, exerted neuroprotective effects against transient focal cerebral ischemia 6 h post-ischemic administration in adult male rats. This study examines its effects on permanent focal cerebral ischemia in adult and aged male rats, which are better models for evaluating treatment outcomes in typical stroke patients. Adult (6-month-old) or aged (18-month-old) male rats subjected to permanent middle cerebral artery occlusion (pMCAO) were continuously administered nestorone (10µg/day) or its vehicle (30% hydroxypropyl-ß-cyclodextrin) for 7 days via an osmotic pump subcutaneously implanted, starting at 18 h post-pMCAO. Nestorone-treated adult male rats showed marked improvements in behavioral outcomes in the adhesive removal and rotarod tests and a significant reduction in infarct size compared to vehicle-treated rats 9 and 30 days post-pMCAO. The same administration of nestorone resulted in apparently comparable neuroprotective effects in aged male rats. The inflammatory mediator NF-κB/p65 was increased in Iba-1 positive cells 24 h post-pMCAO, but was significantly suppressed by subcutaneous injection of nestorone. These results suggested that nestorone exerts long-term neuroprotective effects against permanent focal cerebral ischemia in adult and aged male rats. Nestorone is thus a promising agent for post-stroke treatment owing to its wide age-independent therapeutic time window (18 h after symptom onset), which is longer than that of tPA therapy.

Priority of the basic and instrumental activities of daily living in older patients with cancer prescribed rehabilitation: a cross-sectional survey.

BACKGROUND: There is no information on whether vulnerable older patients with cancer consider basic activities of daily living (BADL) and instrumental activities of daily living (IADL) important outcomes. Our survey aimed to investigate the priority of BADL and IADL in outcomes among vulnerable older patients with cancer. METHODS: This was a single-center survey in a Japanese cancer center. Eligible patients were ≥ 65 years of age and were prescribed in-hospital rehabilitation while under cancer treatment. Using original self-administered ranking questionnaires, patients were asked to rank outcomes and subdomain of BADL and IADL. High-priority domains were defined as the highest, second-highest, and third-highest priority domains in individuals. RESULTS: A total of 169 patients were analyzed. The mean age was 74.0 years (standard deviation, 5.1 years) and the number of males was 107 (63%). The order of ranking of high-priority outcomes was BADL and IADL (n = 155), cognitive function (n = 91), mental function (n = 82), nutrition (n = 61), social function (n = 51), comorbidity (n = 39), and life span (n = 28). The top three high-priority independence subdomains of BADL and IADL were toilet use (n = 140), feeding (n = 134), and mobility (n = 69) among the BADL and shopping (n = 93), food preparation (n = 88), and ability to handle finances (n = 85) among the IADL. CONCLUSIONS: BADL and IADL can be considered the most important health outcomes in clinical trials and in practice among older patients with cancer and physical vulnerabilities.

Effects of intergenerational contact on social capital in community-dwelling adults aged 25-84 years: a non-randomized community-based intervention.

BACKGROUND: Accumulating social capital in urban areas is essential to improve community health. Previous studies suggested that intergenerational contact may be effective for enhancing social capital. However, no study has examined the effect of intergenerational contact on social capital through a population-based evaluation. This study aimed to investigate the effects of a community-based intervention to increase the frequency of intergenerational contact on social capital among adults aged 25-84 years. METHODS: This study used a non-randomized controlled trial design to conduct a community-based intervention (from March 2016 to March 2019). The study area was Tama ward, Kawasaki city, Kanagawa, Japan. The area comprises five districts; one district was assigned as the intervention group and the other four districts as the control group. We provided the intervention to residents in the intervention group. The intervention comprised three phases: Phase 1 was the preparation term (organizing the project committee); Phase 2 was the implementation term (trained volunteer staff members, conducted the intergenerational greeting campaign, and held intergenerational contact events); and Phase 3 was the transition term (surrendering the lead role of the project to the city hall field workers). In the control group, field workers provided public health services as usual. We conducted mail surveys in September 2016 and November 2018 to assess the effects of the intervention on social capital during Phase 2. Eligible participants were randomly selected from community-dwelling adults aged 25-84 years according to age (10,620 control group individuals and 4479 intervention group individuals). We evaluated social trust, norm of reciprocity, and social support as outcome variables. RESULTS: In total, 2518 participants completed both surveys and were analyzed (control group: 1727; intervention group: 791). We found that social trust (coefficient = 0.065; 95% confidence interval [CI]: 0.006, 0.125) and norm of reciprocity (coefficient = 0.084; 95% CI: 0.020, 0.149) positively changed in the intervention group compared with the control group. CONCLUSIONS: This community-based intervention may contribute to sustaining and improving social capital among community-dwelling adults. TRIAL REGISTRATION: UMIN000046769 (UMIN-CTR); first registered on January 28, 2022 (retrospectively registered).

A case of a large solitary fibrous tumor arising from the retroperitoneum resected completely using an intra-aortic balloon.

Solitary fibrous tumors (SFTs) are rare mesenchymal cell-derived tumors that can cause substantial bleeding during surgery due to hyper-vascularization. We report a case of a large retroperitoneal SFT resected completely using an intra-aortic balloon. A 71-year-old female with a history of type 2 diabetes mellitus presented with a tumor that was diagnosed as an insulin-like growth factor-II-producing benign SFT using computed tomography-guided biopsy. The tumor had grown from 6 to 20 cm in diameter within 4 years, with concurrent and severe hypoglycemia. Preoperative computed tomography findings showed substantial blood flow toward the tumor. The retroperitoneal tumor was observed to be widely attached. Substantial hemorrhaging during tumor resection was observed despite vascular embolism. We inflated the intra-aortic balloon for 45 min and resected the tumor completely. In conclusion, large SFT resection requires preoperative tumor blood flow evaluation and preparation of both a vascular embolism and an intra-aortic balloon.

Case of traumatic pulmonary pseudocysts coinciding with vertebral fracture.

Here, we report a case of traumatic pulmonary pseudocysts (TPPs) coinciding with vertebral fracture. Traumatic pulmonary pseudocysts (TPPs) are rare complications of blunt chest trauma. These clinical images of CT, presenting here, seemed to be valuable because they show the process of pseudocyst formation.

Synaptic pruning of murine adult-born neurons by microglia depends on phosphatidylserine.

New neurons, continuously added in the adult olfactory bulb (OB) and hippocampus, are involved in information processing in neural circuits. Here, we show that synaptic pruning of adult-born neurons by microglia depends on phosphatidylserine (PS), whose exposure on dendritic spines is inversely correlated with their input activity. To study the role of PS in spine pruning by microglia in vivo, we developed an inducible transgenic mouse line, in which the exposed PS is masked by a dominant-negative form of milk fat globule-EGF-factor 8 (MFG-E8), MFG-E8D89E. In this transgenic mouse, the spine pruning of adult-born neurons by microglia is impaired in the OB and hippocampus. Furthermore, the electrophysiological properties of these adult-born neurons are altered in MFG-E8D89E mice. These data suggest that PS is involved in the microglial spine pruning and the functional maturation of adult-born neurons. The MFG-E8D89E-based genetic approach shown in this study has broad applications for understanding the biology of PS-mediated phagocytosis in vivo.

Influence of "Face-to-Face Contact" and "Non-Face-to-Face Contact" on the Subsequent Decline in Self-Rated Health and Mental Health Status of Young, Middle-Aged, and Older Japanese Adults: A Two-Year Prospective Study.

This study aims to identify the independent influence of face-to-face contact (FFC) and non-face-to-face contact (NFFC) on the subsequent decline in self-rated health and mental health status by age. A total of 12,000 participants were randomly selected among residents in the study area, and 1751 of them responded to both the 2016 and 2018 mail surveys. The participants were subsequently classified into three age groups (25-49: Young adults; 50-64: Mid-aged adults; and 65-84: Older adults). Social contact was assessed by computing the frequencies of FFC and NFFC. Multiple logistic regression analysis showed the risk of social contact on the decline in self-rated health and World Health Organization-Five Well-Being Index. Both FFC and NFFC were significantly associated with maintaining mental health; however, the impacts of FFC on mental health were more significant than that of NFFC among older adults and young adults. Compared with the no contact group, FFC was significantly associated with maintaining self-rated health in mid-aged adults. The influence of FFC and NFFC on health differed by age group.

[School students' greeting behavior and its association with their community attachment and helping behavior].

Objectives　Many local governments and elementary and junior high schools in Japan have conducted a "greeting campaign". This has been done in order to activate communication among local residents, and to instill public spirit and sociability in students' minds. However, few studies have explored the significance of greeting campaigns. The present study investigates greeting in neighborhoods and its relationship with students' spontaneous greeting behavior. The study also seeks to understand the quantity of greeting in daily life and its association with a student's community attachment and helping behavior.Methods　A self-completion questionnaire survey was conducted with 1,346 students studying in the fourth and higher grades at elementary schools, and 1,357 students in the first and second grade at junior high schools. There were 2,692 valid respondents. We performed the following analyses using the data of elementary school students and junior high school students separately. A partial correlation analysis was conducted wherein gender and grade were introduced as control variables. This analysis tested the correlation between the frequency of being greeted by surrounding people and the frequency of greeting by students, of their own accord. A path analysis that tested the relationship between students' greeting behavior, their attachment to residential areas, and helping behavior was also conducted.Results　The results of the partial correlation analysis revealed that there was a positive correlation between the frequency of being greeted by surrounding people and the frequency of greeting by students, of their own accord, regardless of gender and grade. Moreover, the results of the path analysis revealed that the frequency of being greeted was positively associated with community attachment and that the frequency of students' spontaneous greeting behavior was positively associated not only with community attachment but also with helping behavior. The goodness of model fit was high for both the data of elementary school students as well as the data of junior high school students.Conclusion　We found that exchanging greetings with surrounding people in daily life enhanced students' attachment to the community. In particular, we showed that students' spontaneous greeting behavior led to their helping behavior, which supports the significance of recommending greeting at home, school, or in the local community. Since there was a correlation between the frequency of being greeted and the frequency of greeting willingly, we consider that actions of surrounding adults become important to help students acquire spontaneous greeting behavior.

Quantitative and Qualitative Analyses of Triacylglycerol Production in the Wild-Type Cyanobacterium Synechocystis sp. PCC 6803 and the Strain Expressing AtfA from Acinetobacter baylyi ADP1.

Although cyanobacteria do not possess wax ester synthase/acyl-CoA:diacylglycerol acyltransferase (WS/DGAT), the bacterial enzyme for triacylglycerol (TAG) production, there have been several studies reporting the accumulation of TAG-like compounds in cyanobacteria. In this study, we aimed to evaluate TAG productivity of the ΔrecJ::atfA strain of Synechocystis sp. PCC 6803 generated by inserting atfA encoding WS/DGAT from Acinetobacter baylyi ADP1 into recJ (sll1354), together with the wild type (WT) and the gene-disrupted strain of slr2103 having homology with eukaryotic DGAT2 gene family (Δ2103). Thin-layer chromatography (TLC) of neutral lipids or isolation of the neutral lipid-enriched fraction followed by gas chromatography or liquid chromatography-tandem mass spectrometry was employed for analyses. The ΔrecJ::atfA strain accumulated 0.508 nmol ml-1OD730-1 of TAG after a week of incubation at 100 µmol photons m-2 s-1. The saturated fatty acids C16:0 and C18:0 accounted for about 50% and 20% of the TAG fatty acids, respectively, suggesting that de novo-synthesized fatty acids were preferentially incorporated into TAG molecules. When the neutral lipid profile of the lipid extracts was examined by TLC, a spot located in a slightly lower position compared with the TAG standard was detected in WT but not in the Δ2103 strain. TAG accumulation levels of both strains was only 0.01-0.03 nmol ml-1OD730-1, but the fatty acid composition was substantially different from that of the background. These results suggest that trace amounts of TAG can be produced in Synechocystis cells by enzymes other than Slr2103, and major constituents of the TAG-like spot are unknown lipid species produced by Slr2103.

The 5α-Reductase Inhibitor Finasteride Exerts Neuroprotection Against Ischemic Brain Injury in Aged Male Rats.

Progesterone (P4) exerts potent neuroprotection both in young and aged animal models of stroke. The neuroprotection is likely to be mediated by allopregnanolone (ALLO) metabolized from P4 by 5α-reductase, since the neuroprotection is attenuated by the 5α-reductase inhibitor finasteride, which was done only with young animals though. Thus, we do not know the contribution of ALLO to the P4-induced neuroprotection in aged animals. We examined effects of finasteride on the P4-induced neuroprotection in aged (16-18-month-old) male rats subjected to transient focal cerebral ischemia. Transient focal cerebral ischemia was induced by left middle cerebral artery occlusion (MCAO) and occlusion of the bilateral common carotid arteries. MCAO rats were given an 8 mg/kg P4 6 h after MCAO followed by the same treatment once a day for successive 3 days. Finasteride, a 5α-reductase inhibitor, at 20 mg/kg was intraperitoneally injected 30 min prior to the P4-injections. P4 markedly reduced neuronal damage 72 h after MCAO, and the P4-induced neuroprotection was apparently suppressed by finasteride in the aged animals. However, post-ischemic administration of finasteride alone (20 mg/kg) significantly prevented neuronal damage and the impairment of Rotarod performance after MCAO in aged male rats, but not in young ones. The androgen receptor antagonist flutamide markedly suppressed the neuroprotection of finasteride in the cerebral cortex, but not in the striatum, suggesting the androgen receptor-dependent mechanism of the finasteride-induced neuroprotection in the cerebral cortex. Our findings suggested, for the first time, the potential of finasteride as a therapeutic agent in post-ischemic treatment of strokes in aged population.

Nestorone exerts long-term neuroprotective effects against transient focal cerebral ischemia in adult male rats.

Progesterone (P4) exerts long-term neuroprotective effects in animal models of stroke, and P4 receptors play a crucial role in this neuroprotection. However, it currently remains unclear whether the activation of P4 receptors alone is sufficient to exert long-term neuroprotection because P4 exhibits other steroidogenic and GABAergic activities via several of its metabolites. Nestorone is a potent selective P4 receptor agonist without other steroidogenic and GABAergic activities. Therefore, we examined the effects of nestorone in adult male rats subjected to transient middle cerebral artery occlusion (MCAO). The dose-response relationship of nestorone showed that the 6-h post-ischemic administration of 10 µg/kg nestorone resulted in greater reductions in infarct sizes 48 h after MCAO than the other two doses tested (5 and 80 µg/kg), and this dose of nestorone significantly decreased astrocyte activation in the peri-infarct cortical region. Moreover, 10 µg/kg nestorone significantly prevented functional impairments on the 28th and 29th days and slightly reduced infarct size on the 30th day after MCAO. The present results suggest that the activation of P4 receptors alone is sufficient to exert neuroprotection against transient cerebral ischemia in adult male rats; therefore, nestorone is a promising agent in post-stroke treatment due to its potent progestational effects without other steroid-related activities.

[The relationship between intra- and inter-generational exchange and mental health among young and older adults].

Objective　The purpose of this study was to examine the relationship between intra- and inter-generational exchange and mental health among young adults aged 25-49 years and older adults aged 65-84 years.Methods　In 2016, a community-based, cross-sectional survey was conducted. A total of 3,334 young adults (valid response rate: 24.6%), and 3,116 older adults (valid response rate: 46.0%) completed the survey and were included in the analysis. Their mental health was evaluated using the World Health Organization-Five Well-Being Index (WHO-5), and those who scored under 13 or scored less than one on any item were considered to have poor mental health. To evaluate the intra- or inter-generational exchange, participants were asked about their frequency of interaction with people aged 20-49 years or aged ≥70, excluding family and co-workers. Young adults who interacted with people aged 20-49 years or older adults who interacted with people ≥70 were classified as "having intra-generational exchange," while young adults who interacted with people ≥70 years or older adults who interacted with people aged 20-49 years were classified as "having intergenerational exchange." Therefore, individuals who interacted with both generations were classified as "having multi-generational exchange," and those who did not interact with any generation were categorized as "no exchange." We conducted a logistic regression analysis that included mental health as a dependent variable, intra- and inter-generational exchange as independent variables, and gender, age, educational attainment, marital status, living situation, subjective economic status, social participation, employment, self-rated health, and Instrumental Activity of Daily Living as covariates.Results　Of the 3,334 young adults, 61.5% were mentally healthy, 51.3% had intra-generational exchange, 21.9% had inter-generational exchange, 16.5% had multi-generational exchange, and 42.7% did not have any exchange. Of the 3,116 older adults, 65.8% were mentally healthy, 67.9% had intra-generational exchange, 34.3% had inter-generational exchange, 29.9% had multi-generational exchange, and 21.1% did not have any exchange. A logistic regression analysis revealed that "having intra-generational exchange" and "having intergenerational exchange" were significantly related to better mental health in both young adults (intra-generational; Odds ratios (OR) 1.19, 95% confidence intervals (CI) 1.10-1.30: inter-generational; OR 1.13, 95% CI 1.03-1.25) and older adults (intra-generational; OR 1.15, 95% CI 1.02-1.29: inter-generational; OR 1.46, 95% CI 1.30-1.65). Therefore, "having multi-generational exchange" was more strongly related to better mental health compared with "only having intra-generational exchange."Conclusion　Among young and older adults, intra- and inter-generational exchange were related to better mental health, and multi-generational exchange showed the strongest relationship with better mental health.

Progesterone improves functional outcomes after transient focal cerebral ischemia in both aged male and female rats.

Progesterone hormone (P4) is a promising agent against strokes because post-ischemic administration of P4 exerts neuroprotective effects in several young and aged animal models of stroke. However, in contrast to a majority of the studies using male animals, female animals remain underrepresented. In addition, we do not know whether the same administration way of P4 is effective in both male and female animals because there are gender different responses to steroid hormones and stroke. In this study, we thus evaluated long-term histological and functional outcomes in the same treatment with P4 in both 18-month old male and age-matched female rats subjected to transient middle cerebral artery occlusion (MCAO). MCAO aged male and female rats were given a subcutaneous injection of P4 (4 mg/kg) 6 h after MCAO followed by once daily for successive 7 days. The post-ischemic administration of P4 significantly improved the impairments of spatial working memory and motor coordination 28-29 days after MCAO in both aged male and age-matched female rats. However, the P4 administration slightly but not significantly reduced infarct sizes 30 days after MCAO in aged female rats, in contrast to significant better histological outcome in P4-treated aged males. On the other hand, these histological and behavioral analyses showed no adverse effects of P4 in aged rats of both sexes. Collectively, our study provides preclinical evidence to prompt further preclinical studies for post-stroke treatment with P4 and the translation of its clinical trials in old stroke patients of both sexes.

[Community Child-Rearing Support Scale: Applicability across generations and differences in the supportive behaviors among generations].

Objectives　Using the Community Child-Rearing Support Scale (CCRSS), which was developed for older adults, we examined 1) the reliability and validity of the scale for multiple generations, as well as the generational differences in the 2) degree and content of supportive behaviors for child rearing and 3) correlates of the behavior, in conjunction with gender differences.Methods　A mail survey was conducted with residents aged 25-84 years who were randomly selected from two cities in Tokyo and the surrounding areas, and responses were obtained from 8918 residents (response rate: 33%). The respondents were grouped as follows: old-aged (65-84 years), middle-aged (50-64 years), and young-aged (25-49 years). We performed the following analyses by age group and gender: 1) Cronbach's reliability coefficient and a confirmatory factor analysis of the CCRSS, 2) analysis of variance of the total CCRSS scores and scores of the three subscales ("children's security and sound growth," "instrumental support to parents," and "emotional support to parents"), and 3) a multiple regression analysis of the total scores in which various individual characteristics were introduced as explanatory variables.Results　The reliability coefficient was over 0.85 for each age group, and the factor analysis showed good model fitness. Compared to the middle- and young-aged groups, the old-aged group was more likely to provide support for "children's security and sound growth," and equally (for women) or more likely (for men) to provide "emotional support to parents," thereby resulting in the highest total score among the three generations. The mean score of "instrumental support to parents," such as taking care of a child, was the highest for young women, although the score was low overall. Having a child or grandchild under 13 years old and stronger generativity were positively associated with child-rearing support for all age groups; however, the degree of associations varied across the groups. While having a child was strongly associated with support among the young-aged group, the association between support and generativity was stronger for older groups. Moreover, participation in neighborhood associations or volunteer groups and high school or lower education were associated with more support among all age groups, whereas living in rental apartments was associated with less support among the young-aged group.Conclusion　Our findings suggest that the CCRSS can be used for multiple generations and that old people play an important role in child rearing in the community. We found both differences and similarities between generations with respect to the correlates of child-rearing support.

Direct Synthesis of Prussian Blue Nanoparticles in Liposomes Incorporating Natural Ion Channels for Cs+ Adsorption and Particle Size Control.

Coordination polymer (CP) nanoparticles (NPs) formed by a self-assembly of organic ligands and metal ions are one of the attractive materials for molecular capture and deliver/release in aqueous media. Control of particle size and prevention of aggregation among CP NPs are important factors for improving their adsorption capability in water. We demonstrate here the potential of a liposome incorporating an antibiotic ion channel as a vessel for synthesizing Prussian blue (PB) NPs, being a typical CP. In the formation of PB NPs within liposomes, the influx rate of Fe2+ ions into liposome encapsulated [Fe(CN)6]3- through channels was fundamental for the change of NPs' sizes. The optimized PB NP-liposome composite showed higher adsorption capacity of Cs+ ions than that of aggregated PB NPs that are prepared without liposome in aqueous media.

High-fidelity entanglement swapping and generation of three-qubit GHZ state using asynchronous telecom photon pair sources.

We experimentally demonstrate a high-fidelity entanglement swapping and a generation of the Greenberger-Horne-Zeilinger (GHZ) state using polarization-entangled photon pairs at telecommunication wavelength produced by spontaneous parametric down conversion with continuous-wave pump light. While spatially separated sources asynchronously emit photon pairs, the time-resolved photon detection guarantees the temporal indistinguishability of photons without active timing synchronizations of pump lasers and/or adjustment of optical paths. In the experiment, photons are sufficiently narrowed by fiber-based Bragg gratings with the central wavelengths of 1541 nm & 1580 nm, and detected by superconducting nanowire single-photon detectors with low timing jitters. The observed fidelities of the final states for entanglement swapping and the generated three-qubit state were 0.84 ± 0.04 and 0.70 ± 0.05, respectively.

Location and thickness of delaminated rotator cuff tears: cross-sectional analysis with surgery record review.

BACKGROUND: To facilitate better treatment, we analyzed morphologic features of delamination from the viewpoint of the location of delamination and the thickness of each layer. MATERIALS AND METHODS: Of 270 shoulders that consecutively underwent arthroscopic rotator cuff repair, 210 were included. During the operation, the surgeon assessed the size of the rotator cuff tear, determined the presence and location of delamination, and compared the thickness between superficial and deep layers if delamination was present. Immediately after the operation, the surgeon wrote down the data in the record form. The authors retrospectively referred to these surgical records to investigate those items. RESULTS: Delamination was found in 111 of 210 shoulders. The overall preoperative Constant score did not significantly differ between the 2 groups. In terms of the location, 7.2% cases had delamination in the anterior part, 74.8% in the posterior part, and 18.0% in both parts (Fleiss κ = 0.9). The larger the rotator cuff tear, the more frequently the delamination was limited to the posterior part (trend P = .001). As for layer thickness comparison, 40.0% of the shoulders with small tears, 38.8% with medium tears, 66.0% with large tears, and 80.0% with massive tears had a thicker deep layer than superficial layer (Fleiss κ = 0.9). The larger the size of the rotator cuff tear, the more frequently the deep layer was thicker than the superficial layer (trend P = .001). CONCLUSIONS: The larger the rotator cuff tear, the more carefully shoulder surgeons should observe and treat the posterior and deep part of delamination.

Neuronal PAS domain protein 4 (Npas4) controls neuronal homeostasis in pentylenetetrazole-induced epilepsy through the induction of Homer1a.

Neuronal intrinsic homeostatic scaling-down of excitatory synapse has been implicated in epilepsy pathogenesis to prevent the neuronal circuits from hyperexcitability. Recent findings suggest a role for neuronal PAS domain protein 4 (Npas4), an activity-dependent neuron-specific transcription factor in epileptogenesis, however, the underlying mechanism by which Npas4 regulates epilepsy remains unclear. We herein propose that limbic seizure activity up-regulates Npas4-homer1a signaling in the hippocampus, thereby contributing to epileptogenesis in mice. The expression level of Npas4mRNA was significantly increased after the pentylenetetrazol (PTZ) treatment. Npas4KO mice developed kindling more rapidly than their wild-type littermates. The expression of Homer1a in the hippocampus increased after seizure activity. Npas4 increased Homer1a promoter activity in COS7 cells. The PTZ-stimulated induction of Homer1a was attenuated in the hippocampus of Npas4KO mice. The combination of fluorescence in situ hybridization and immunohistochemical analyses revealed that Homer1amRNA co-localized with the Npas4 protein after the convulsive seizure response. PTZ reduced excitatory synaptic transmission at the associational/commissural fibers-CA3 synapses through the Npas4-mediated down-regulation of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in hippocampal CA3 neurons. The adeno-associated virus (AAV)-mediated expression of Homer1a resulted in lower α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor GluA1 subunit levels in the hippocampal plasma membrane fraction than in that from AAV-EGFP-transfected Npas4KO mice. The development of kindling was more strongly suppressed in AAV-Homer1a-microinjected Npas4KO mice than in AAV-EGFP-microinjected Npas4KO mice. These results indicate that Npas4 functions as a molecular switch to initiate homeostatic scaling and the targeting of Npas4-Homer1a signaling may provide new approaches for the treatment of epilepsy.

High visibility Hong-Ou-Mandel interference via a time-resolved coincidence measurement.

A high visibility Hong-Ou-Mandel (HOM) interference between two independently prepared photons plays an important role in various photonic quantum information processing. In a standard HOM experiment using photons generated by pulse-pumped spontaneous parametric down conversion (SPDC), larger detection time windows than the coherence time of photons have been employed for measuring the HOM visibility and/or drawing the HOM dip. If large amounts of stray photons continuously exist within the detection time windows, employing small detection time windows is favorable for reducing the effect of background noises. Especially, such a setup is helpful for the HOM experiment using continuous wave (cw)-pumped SPDC and the time-resolved coincidence measurement. Here we argue that the method for determining the HOM visibility used in the previous cw experiments tends to suffer from distortion arising from biased contribution of the background noises. We then present a new method with unbiased treatment of the cw backgrounds. By using this method, we experimentally demonstrate a high visibility HOM interference of two heralded telecom photons independently generated by SPDC with employing cw pump light. An observed HOM visibility is 0.87 ± 0.04, which is as high as those observed by using pulse-pumped SPDC photons.