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The effects of the 1990s reforms to the electoral system of Japan's House of Representatives have been among the most frequently discussed topics in political science research on the country. These reforms saw the replacement of a hitherto single nontransferable vote (SNTV) system by a mixed-member majoritarian (MMM) system with a strong Single Member District (SMD) and a weaker Proportional Representation (PR) component. Many studies have suggested that the reforms may have had significant impact on the strategies of political parties. Generally, SMD systems have been widely thought to favor larger parties, while PR systems are more beneficial to small and medium-sized parties. On the content side, larger parties seeking control of the government would try to win the support of large numbers of floating voters by campaigning on universal/programmatic policy appeals, as opposed to particularistic interests. In contrast, smaller parties would cater towards their core supporters’ preferences. Previous studies have noted that the old SNTV system in Japan had produced results similar to PR systems (Reed 2003). Japan's electoral reform may have thus changed the strategy of large parties, which would need to win more seats in the SMDs to gain (or hold onto) power, while smaller parties have continued to try and win seats via the PR tier. Therefore, the reform provides valuable research material in so far as we can simultaneously observe different effects by the SMD and the PR systems on parties of different sizes.

Supplementary Figure 1 from Regulation of Estrogen-Dependent Transcription by the LIM Cofactors CLIM and RLIM in Breast Cancer

Supplementary Figure 3 from Regulation of Estrogen-Dependent Transcription by the LIM Cofactors CLIM and RLIM in Breast Cancer

Supplementary Figure 5 from Regulation of Estrogen-Dependent Transcription by the LIM Cofactors CLIM and RLIM in Breast Cancer

Supplementary Table 1 from Regulation of Estrogen-Dependent Transcription by the LIM Cofactors CLIM and RLIM in Breast Cancer

Supplementary Figure 4 from Regulation of Estrogen-Dependent Transcription by the LIM Cofactors CLIM and RLIM in Breast Cancer

Background Persistent creatine kinase (CK) elevation can occur due to various conditions. Identifying the causes of hyperCKemia is crucial for enabling appropriate follow-up and care. Girls with elevated CK levels may be carriers of Duchenne/Becker muscular dystrophy (DMD/BMD), making diagnosis more difficult than that in boys. This study aimed to elucidate the underlying causes of high CK levels in girls. Methods Fourteen girls (seven symptomatic, seven asymptomatic) with persistently elevated CK levels but without a family history of muscle diseases were referred to our hospital between April 2014 and August 2018. Muscle biopsy and/or genetic analysis were conducted for diagnoses. Results Among the symptomatic girls, six (85.7%) had muscular dystrophy (five DMD/BMD carriers, and one sarcoglycanopathy [limb-girdle muscular dystrophy: LGMDR4]), and one had dermatomyositis. Among the asymptomatic girls, four (57.1%) had muscular dystrophy (three DMD/BMD carriers, and one calpainopathy [LGMDR1]), and three were undiagnosed. Conclusion Our results indicate that muscular dystrophy, including DMD/BMD carriers, must be considered in girls with highperCKemia regardless of symptoms presentation, and in symptomatic girls with dermatomyositis. Investigations in girls with hyperCKemia should be performed under proper ethical considerations. Further research is necessary to develop a diagnostic strategy for girls with hyperCKemia.

The COVID-19 pandemic has had a profound impact on societies, with possible consequences for their fundamental values. Modernization theory links societal values to the underlying subjective sense of existential security in a given society (scarcity hypothesis), while also claiming that values remain stable once individuals reach adulthood (socialization hypothesis). An acute existential crisis such as the COVID-19 pandemic offers a rare opportunity to test these assumptions. We analyze data from representative surveys conducted shortly before and after the onset of the pandemic. Remaining survey sample differences are statistically controlled via propensity score weighting and regression adjustment, while post-stratification weights are used to allow conclusions about the Japanese population. In three sets of analyses, we reveal that the pandemic and the experienced psychological distress are negatively associated with emancipative and secular values, entailing a reversal to traditionalism, intolerance, and religiosity. First, we document a substantial decline in both emancipative and secular values in the first months of the pandemic compared to five months earlier and this decline remained stable a year later. Second, we present some evidence that value change was stronger in prefectures more severely affected by the pandemic. Third, individuals who experienced stronger psychological distress emphasized the same values more strongly, as evident in two surveys from May 2020 and April 2021. In contrast to the socialization hypothesis, our study provides evidence that, under extraordinary environmental conditions, values can change even within a negligibly short time period.

Otitis media (OM) is common among young children and is related to hearing loss. We investigated the association between maternal insecticide use, from conception to the first and second/third trimesters, and OM events in children in the first year of age. Data from Japan Environment and Children's Study were used in this prospective cohort study. Characteristics of patients with and without history of OM during the first year of age were compared. The association between history of OM in the first year and insecticide use was evaluated using logistic regression analysis. The study enrolled 98,255 infants. There was no significant difference in the frequency of insecticide use between groups. Insecticide use of more than once a week from conception to the first trimester significantly increased the occurrence of OM in children in the first year (odds ratio [OR] = 1.30, 95% confidence interval [CI] 1.01–1.67). The association between OM in the first year and insecticide use from conception to the first trimester was only significant in the group without daycare attendance (OR 1.76, 95% CI 1.30–2.38). Maternal insecticide use more than once a week from conception to the first trimester significantly increased OM risk in offspring without daycare attendance.

Objective This study aimed to investigate the associations between psychopathological characteristics of children and adolescents with primary headache, as measured by the Strengths and Difficulties Questionnaire (SDQ), and treatment outcomes. Methods A cohort study was conducted on 124 pediatric patients with primary headache. At the first consultation, the SDQ was completed by the parents. The analysis of treatment efficacy was conducted on 90 patients with a follow-up period of at least one year. Treatment responders were defined as those who showed 50% reduction in the headache frequency. First, an analysis of the SDQ total scores and five subscales, among the migraine and tension-type headache groups, was conducted for 124 participants. Second, the association between the SDQ scores and treatment outcomes in the groups with periods of improvement of less than three months and three months or more were analyzed in 90 patients. Results Migraine patients displayed more difficulties than strengths in terms of the total score (p = .004) and in the emotional symptoms subscale (p = .012) compared with tension-type headache patients. Migraine patients who required more than three months to show improvement displayed more peer problems (p = .020), while tension-type headache patients who required more than three months to show improvement displayed fewer conduct problems (p = .007). Conclusion Evaluation of patient characteristics using the SDQ at first consultation can predict the treatment outcome. Moreover, it can help provide appropriate initial treatment and improve outcome of primary headache in children.

This study aimed to clarify the effects of television/digital versatile disc (TV/DVD) viewing time and portable electronic device (PED) usage time on sleep duration and bedtime and the difference between the effects of TV/DVD and PED on sleep. The effect of TV/DVD viewing time or PED usage time on sleep duration and bedtime was analyzed using a multiple logistic regression analysis adjusted for covariates. A total of 74,525 participants were included in the analysis, using data from Japan Environment and Children’s Study. TV/DVD viewing was not associated with short sleep duration, but PED usage was associated with short sleep duration. In addition, the risk of short sleep duration increased as PED usage time increased. We also investigated the effects of sleep habits at age 1 year on sleep at age 3 years. This study showed that late bedtime at age 1 year posed a significant risk of late bedtime at age 3 years. In summary, particular caution should be paid to PED use from a child’s health perspective, and sleep habits should be focused on bedtime from the age of 1 year.

Glycogen storage disease type Ia (GSDIa) is an autosomal recessive disorder caused by glucose-6-phosphatase (G6PC) deficiency. GSDIa causes not only life-threatening hypoglycemia in infancy, but also hepatocellular adenoma as a long-term complication. Hepatocellular adenoma may undergo malignant transformation to hepatocellular carcinoma. New treatment approaches are keenly anticipated for the prevention of hepatic tumors. Gene replacement therapy (GRT) is a promising approach, although early treatment in infancy is essential for its safety and efficiency. Thus, GRT requires screening systems for early disease detection. In this study, we developed a screening system for GSDIa using dried blood spots (DBS) on filter paper, which can detect the most common causative mutation in the East-Asian population, c.648G>T in the G6PC gene. Our system consisted of nested PCR analysis with modified competitive oligonucleotide priming (mCOP)-PCR in the second round and melting curve analysis of the amplified products. Here, we tested 54 DBS samples from 50 c.648G (wild type) controls and four c.648T (mutant) patients. This system, using DBS samples, specifically amplified and clearly detected wild-type and mutant alleles from controls and patients, respectively. In conclusion, our system will be applicable to newborn screening for GSDIa in the real world.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder that results in progressive muscle atrophy and weakness. As new therapies for SMA have been developed, newborn screening for SMA can lead to early diagnosis and treatment. The objective of this study was to gather the general population’s view on screening of SMA in newborns in Japan. A questionnaire survey was conducted on two general population groups in Japan. A total of 269 valid responses were obtained. In the general population, about half of the participants had no knowledge about SMA, and more than 90% did not know about new therapies for SMA. Conversely, more than 95% of the general population agreed with screening newborns for SMA because they believed that early diagnosis was important, and treatments were available. This study revealed that the general population in Japan mostly agreed with screening for SMA in newborns even though they did not know much about SMA. Newborn screening for SMA is promising, but it is in very early stages. Therefore, SMA newborn screening should be performed with sufficient preparation and consideration in order to have a positive impact on SMA patients and their families.

Recently, increasing research attention has been given to the development of an absorber to enhance the coefficient of performance (COP) and the capacity of an adsorption heat pump by improving the sorbent in the sorption chamber or reactor. This study introduces the preparation method for an efficient adsorbent with a high thermal conductivity. Three types of host matrix aluminum composite sorbents were prepared through anodizing and pore widening treatment (PWT). This created an aluminum oxide film that was 92 μm thick with a mean pore diameter of 76 nm on an aluminum plate. To improve the sorption ability, the anodized aluminum was impregnated with calcium chloride. The sorption isotherm of the aluminum composite demonstrated its ability to uptake 7.5 mol-H2O/mol-CaCl2 water at a relative pressure of 0.33 at 30 °C. A numerical method was used to predict water sorption and temperature distribution in the aluminum composite layer via a heat and mass transfer model. The specific cooling power (SCP) was used to indicate the cooling performance of a sorption heat pump that employed the aluminum composite as laminate sorbent fins by varying the spacing between each fin.

Spinal muscular atrophy (SMA), an inherited disease of motor neuron dysfunction, results from insufficient levels of the survival motor neuron (SMN) protein. Movement of the SMN protein as granules within cultured axons suggests that the pathogenesis of SMA may involve defects in neuronal transport, yet the nature of axon transport vesicles remains enigmatic. Here we show that SMN directly binds to the α-subunit of the coat protein I (COPI) vesicle coat protein. The α-COP protein co-immunoprecipitates with SMN, small nuclear ribonucleoprotein-associated assembly factors and β-actin mRNA. Although typically Golgi associated, in neuronal cells α-COP localizes to lamellipodia and growth cones and moves within the axon, with a subset of these granules traveling together with SMN. Depletion of α-COP resulted in mislocalization of SMN and actin at the leading edge at the lamellipodia. We propose that neurons utilize the Golgi-associated COPI vesicle to deliver cargoes necessary for motor neuron integrity and function.

The developmental activity of LIM homeodomain transcription factors (LIM-HDs) is critically controlled by LIM domain-interacting cofactors of LIM-HDs (CLIM, also known as NLI or LDB). CLIM cofactors associate with single-stranded DNA binding proteins (SSDPs, also known as SSBPs) thereby recruiting SSDP1 and/or SSDP2 to LIM-HD/CLIM complexes. Although evidence has been presented that SSDPs are important for the activity of specific LIM-HD/CLIM complexes, the developmental roles of SSDPs are unclear. We show that SSDP1a and SSDP1b mRNAs are widely expressed early during zebrafish development with conspicuous expression of SSDP1b in sensory trigeminal and Rohon–Beard neurons. SSDP1 and CLIM immunoreactivity co-localize in these neuronal cell types and in other structures. Over-expression of the N-terminal portion of SSDP1 (N-SSDP1), which contains the CLIM-interaction domain, increases endogenous CLIM protein levels in vivo and impairs the formation of eyes and midbrain–hindbrain boundary. In addition, manipulation of SSDP1 via N-SSDP1 over-expression or SSDP1b knock down impairs trigeminal and Rohon–Beard sensory axon growth. We show that N-SSDP1 is able to partially rescue the inhibition of axon growth induced by a dominant-negative form of CLIM (DN-CLIM). These results reveal specific functions of SSDP in neural patterning and sensory axon growth, in part due to the stabilization of LIM-HD/CLIM complexes.

Randomized experiments are becoming increasingly common in political science. Despite their well-known advantages over observational studies, randomized experiments are not free from complications. In particular, researchers often cannot force subjects to comply with treatment assignment and to provide the requested information. Furthermore, simple randomization of treatments remains the most commonly used method in the discipline even though more efficient procedures are available. Building on the recent statistical literature, we address these methodological issues by offering general recommendations for designing and analyzing randomized experiments to improve the validity and efficiency of causal inference. We also develop an ew statistical methodology to explore causal heterogeneity. The proposed methods are applied to a survey experiment conducted during Japan’s 2004 Upper House election, where randomly selected voters were encouraged to obtain policy information from political parties’ websites. An R package is publicly available for implementing various methods useful for designing and analyzing randomized experiments.

beta-Catenin is an example of a typical molecule that can be translocated bidirectionally through nuclear pore complexes (NPCs) on its own in a facilitated manner. In this work the nuclear import and export of beta-catenin were examined to compare the sequence requirement of this molecule and to determine whether molecular interactions required for its bidirectional NPC passage are distinct or not. Deletion analysis of beta-catenin revealed that armadillo repeats 10-12 and the C terminus comprise the minimum region necessary for nuclear migration activity. Further dissection of this fragment showed that the C terminus tail plays an essential role in nuclear migration. The region of beta-catenin required for export substantially overlapped the region required for import. Therefore, the NPC translocation of beta-catenin is apparently reversible, which is consistent with findings reported previously. However, different translocating molecules blocked nuclear import and export of beta-catenin differentially. The data herein indicate that beta-catenin shows an overlapping sequence requirement for its import and export but that bidirectional movement through the NPC proceeds through distinct molecular interactions.

目的. がん告知におけるかかりつけ医の重要性について, 段階的告知の観点から検証する. 方法. 1999年2月から2001年10月の間に, 胸部異常陰影の精査目的で大阪医科大学付属病院を受診した患者82名に不安テスト (state-trait anxiety inventory: STAI) を行い, 特性不安, 状態不安, さらにその差を不安増強指数として, 患者の性別, 年齢, 付き添いの有無, 最終診断 (肺癌であったか否か), 紹介元 (検診群{検診結果通知により直接受診} とかかりつけ医群 {かかりつけ医からの紹介受診}) について比較検討した. 結果. 不安増強指数の比較では, 性別, 年齢, 付き添いの有無, 最終診断については, 有意な差はなかったが, 紹介元では, 検診群7.6±8.8, かかりつけ医群3.5±8.6で, 有意差がみられた (p=0.0358). つまり, 病状について, 何の説明も受けずに受診した検診群に比べ, かかりつけ医からなんらかの説明を受けているかかりつけ医群の方が, 不安の増強が少なかった. 結論. かかりつけ医の説明が, がん告知に有効であると言われている段階的告知の一部となり, 患者の不安を軽減したものと思われ, かかりつけ医のがん告知に果たす役割は大きいと考えられる.

In mice, the ubiquitin ligase RLIM/Rnf12 is a critical survival factor for mammary milk-producing alveolar cells, but little is known about how its activity is regulated. It is shown here that RLIM shuttles between the nucleus and cytoplasm in a phosphorylation-dependent manner, and shuttling is important for its alveolar survival function., The X-linked gene Rnf12 encodes the ubiquitin ligase really interesting new gene (RING) finger LIM domain–interacting protein (RLIM)/RING finger protein 12 (Rnf12), which serves as a major sex-specific epigenetic regulator of female mouse nurturing tissues. Early during embryogenesis, RLIM/Rnf12 expressed from the maternal allele is crucial for the development of extraembryonic trophoblast cells. In contrast, in mammary glands of pregnant and lactating adult females RLIM/Rnf12 expressed from the paternal allele functions as a critical survival factor for milk-producing alveolar cells. Although RLIM/Rnf12 is detected mostly in the nucleus, little is known about how and in which cellular compartment(s) RLIM/Rnf12 mediates its biological functions. Here we demonstrate that RLIM/Rnf12 protein shuttles between nucleus and cytoplasm and this is regulated by phosphorylation of serine S214 located within its nuclear localization sequence. We show that shuttling is important for RLIM to exert its biological functions, as alveolar cell survival activity is inhibited in cells expressing shuttling-deficient nuclear or cytoplasmic RLIM/Rnf12. Thus regulated nucleocytoplasmic shuttling of RLIM/Rnf12 coordinates cellular compartments during mammary alveolar cell survival.

This chapter explores the link between electoral reforms and structural changes in the social bases of party support in Italy and Japan. Italy and Japan offer important case studies as they underwent significant electoral reform in the early 1990s as part of a more general process of political change. Both in Italy and Japan, corruption scandals and increasing public dissatisfaction with politicians resulted in demands for electoral reform. Electoral reform was seen as an institutional means of changing the system of political representation to promote alternation of parties in power, increase transparency and efficiency in government, and reduce the opportunities and incentives for corruption (Katz 2001; Reed and Thies 2001a).

To ensure that female mammals do not have an excess of X-chromosome gene products, one of the two X chromosomes present in each cell is silenced. During embryogenesis, the imprinted form of this X-chromosome inactivation (XCI) process selectively silences the paternal X following the detection of Xist RNA expression on the paternal X chromosome (Xp) at about the four-cell stage of embryonic development. Later, an embryonic form of XCI occurs in the developing blastocyst of the embryo proper, inactivating either the paternal or maternal X chromosome at random. Using mouse genetics, Shin et al. show that maternal deposits of Rnf12/RLIM ubiquitin ligase are crucial in the initiation of the initial process, but not in the later random X inactivation. Two forms of X-chromosome inactivation ensure the selective silencing of female sex chromosomes in mouse embryos. Imprinted silencing begins with the detection of Xist RNA expression on the paternal X chromosome at about the four-cell stage of development. Later, a random form of inactivation silences either the paternal or the maternal X chromosome. Here it is shown that maternal deposits of the ubiquitin ligase Rnf12/RLIM are required for the imprinted form of X-chromosome inactivation. Two forms of X-chromosome inactivation (XCI) ensure the selective silencing of female sex chromosomes during mouse embryogenesis. Imprinted XCI begins with the detection of Xist RNA expression on the paternal X chromosome (Xp) at about the four-cell stage of embryonic development. In the embryonic tissues of the inner cell mass, a random form of XCI occurs in blastocysts that inactivates either Xp or the maternal X chromosome (Xm)1,2. Both forms of XCI require the non-coding Xist RNA that coats the inactive X chromosome from which it is expressed. Xist has crucial functions in the silencing of X-linked genes, including Rnf12 (refs 3, 4) encoding the ubiquitin ligase RLIM (RING finger LIM-domain-interacting protein). Here we show, by targeting a conditional knockout of Rnf12 to oocytes where RLIM accumulates to high levels, that the maternal transmission of the mutant X chromosome (Δm) leads to lethality in female embryos as a result of defective imprinted XCI. We provide evidence that in Δm female embryos the initial formation of Xist clouds and Xp silencing are inhibited. In contrast, embryonic stem cells lacking RLIM are able to form Xist clouds and silence at least some X-linked genes during random XCI. These results assign crucial functions to the maternal deposit of Rnf12/RLIM for the initiation of imprinted XCI.

Mammary oncogenesis is profoundly influenced by signaling pathways controlled by estrogen receptor α (ERα). Although it is known that ERα exerts its oncogenic effect by stimulating the proliferation of many human breast cancers through the activation of target genes, our knowledge of the underlying transcriptional mechanisms remains limited. Our published work has shown that the in vivo activity of LIM homeodomain transcription factors (LIM-HD) is critically regulated by cofactors of LIM-HD proteins (CLIM) and the ubiquitin ligase RING finger LIM domain-interacting protein (RLIM). Here, we identify CLIM and RLIM as novel ERα cofactors that colocalize and interact with ERα in primary human breast tumors. We show that both cofactors associate with estrogen-responsive promoters and regulate the expression of endogenous ERα target genes in breast cancer cells. Surprisingly, our results indicate opposing functions of LIM cofactors for ERα and LIM-HDs: whereas CLIM enhances transcriptional activity of LIM-HDs, it inhibits transcriptional activation mediated by ERα on most target genes in vivo. In turn, the ubiquitin ligase RLIM inhibits transcriptional activity of LIM-HDs but enhances transcriptional activation of endogenous ERα target genes. Results from a human breast cancer tissue microarray of 1,335 patients revealed a highly significant correlation of elevated CLIM levels to ER/progesterone receptor positivity and poor differentiation of tumors. Combined, these results indicate that LIM cofactors CLIM and RLIM regulate the biological activity of ERα during the development of human breast cancer. [Cancer Res 2009;69(1):128–36]

Complexes composed of multiple proteins regulate most cellular functions. However, our knowledge about the molecular mechanisms governing the assembly and dynamics of these complexes in cells remains limited. The in vivo activity of LIM homeodomain (LIM-HD) proteins, a class of transcription factors that regulates neuronal development, depends on the high-affinity association of their LIM domains with cofactor of LIM homeodomain proteins (LIM-HDs) (CLIM, also known as Ldb or NLI). CLIM cofactors recruit single-stranded DNA-binding protein 1 (SSDP1, also known as SSBP3), and this interaction is important for the activation of the LIM-HD/CLIM protein complex in vivo . Here, we identify a cascade of specific protein interactions that protect LIM-HD multiprotein complexes from proteasomal degradation. In this cascade, CLIM stabilizes LIM-HDs, and SSDP1 stabilizes CLIM. Furthermore, we show that stabilizing cofactors prevent binding of ubiquitin ligases to multiple protein interaction domains in LIM-HD recruited protein complexes. Together, our results indicate a combinatorial code that selects specific multiprotein complexes via proteasomal degradation in cells with broad implications for the assembly and specificity of multiprotein complexes.

Mongolian gerbil 2-cell embryos were cultured in modified M16. When osmolarity of the medium with 5.0 mmol glucose l(-1) was varied by adjusting the amount of NaCl added, 2-cell embryos at 280, 290, 300 and 310 mOsmol developed to the 8- and 16-cell stages. The incorporation and oxidation of 14C-Methionine were compared between fresh recovered and cultured embryos at the 1-cell to 16-cell stages. Development beyond the 8-cell stage of fresh recovered embryos showed an enhanced rate of total protein synthesis, indicating activation of the transcription process of the embryonic genome. However, we found that the lowest incorporation and oxidation of 14C-Methionine was observed in cultured embryos of the 16-cell stage at 115 h after hCG injection. In the medium without phosphate, glucose promoted development of 2-cell embryos to the 8-cell stage, and low concentrations of glucose were necessary for the development of the 2-cell to 8-cell stages. These results suggest that Mongolian gerbil preimplantation embryos can be cultured in vitro in a chemically defined medium with a low concentration of glucose.