Rpd3/CoRest-mediated activity-dependent transcription regulates the flexibility in memory updating in Drosophila

Consolidated memory can be preserved or updated depending on the environmental change. Although such conflicting regulation may happen during memory updating, the flexibility of memory updating may have already been determined in the initial memory consolidation process. Here, we explored the gating mechanism for activity-dependent transcription in memory consolidation, which is unexpectedly linked to the later memory updating in Drosophila. Through proteomic analysis, we discovered that the compositional change in the transcriptional repressor, which contains the histone deacetylase Rpd3 and CoRest, acts as the gating mechanism that opens and closes the time window for activity-dependent transcription. Opening the gate through the compositional change in Rpd3/CoRest is required for memory consolidation, but closing the gate through Rpd3/CoRest is significant to limit future memory updating. Our data indicate that the flexibility of memory updating is determined through the initial activity-dependent transcription, providing a mechanism involved in defining memory state

The Socioeconomic Factors Affecting the Mental Health Status of Family Caregivers of Type 2 Diabetic Patients

As Japan’s ‘super aged society’ develops, more and more aged caregivers are obliged to take care of patients with chronic diseases. In this study, the family caregivers of type 2 diabetic patients were targeted to identify the socioeconomic conditions that affect their mental health status. The results indicated that when the caregivers were overly concerned about the patients’ care, they had higher GHQ （General Health Questionnaire） scores（ r=.685, p<0.05）. On the other hand, the more caregivers spoke frankly about their feelings to the patients, the lower their GHQ Likert Scores were（ r=.-718, p<0.05）. Suggestions for medical staff were made to establish a support system not only for type 2 diabetic patients, but also for the family caregivers of these patients

A Second Look or, Not to Mention the Occasional Capsizing of a Windsurfer

Of all of the epithelial ovarian cancers (EOC), clear cell adenocarcinoma (CCA) has the worst clinical prognosis. Furthermore, the conventional EOC biomarker CA125 is more often negative in CCA than in other subtypes of EOC. This study sought to discover a new diagnostic biomarker that would allow more reliable detection of CCA. Using mass spectrometry, we compared proteins in conditioned media from cell lines derived from CCA and other types of EOC. We identified 30 extracellular or released proteins specifically present in CCA-derived cell lines. Bioinformatics analyses identified a serine protease inhibitor, tissue factor pathway inhibitor 2 (TFPI2), as a potential biomarker for CCA. Real time RT-PCR and Western blot analyses revealed that TFPI2 was exclusively expressed in CCA-derived cell lines and tissues. For clinical validation, we measured levels of TFPI2 and CA125 in a set of sera from 30 healthy women, 30 patients with endometriosis, and 50 patients with CCA, using an automated enzyme-linked immunosorbent assay systems. Serum levels of TFPI2 were significantly elevated in CCA patients, even those with normal CA125 levels. In terms of area under the receiver operating characteristic curve (AUC), TFPI2 was superior to CA125 in discriminating CCA patients from healthy women (AUC 0.97 for TFPI2 versus AUC 0.80 for CA125), or from patients with endometriosis (AUC 0.93 for TFPI2 versus 0.80 for CA125). This is the first evidence for TFPI2 as a serum biomarker of CCA. We propose that this biomarker may be useful for detection of CCA and for monitoring the transformation from endometriosis into CCA

Interaction Rating Scale (IRS) as an Evidence-Based Practical Index of Children’s Social Skills and Parenting

Background: The purpose of this paper is to describe the features of the Interaction Rating Scale (IRS) as an evidence-based practical index of children’s social skills and parenting.Methods: The participants in our study, which was conducted as part of a Japan Science and Technology Agency (JST) project, were 370 dyads of children (aged 18, 30, and 42 month) and 81 dyads of 7-year-old children with their caregivers. The participants completed the five minute interaction session and were observed using the IRS.Results: The results indicated that the IRS can measure children’s social skill development and parenting with high validity. Along with the discriminate validity for pervasive development disorder (PDD), attention-deficit/hyperactivity disorder (ADHD), abuse and maltreatment, a high correlation with the SDQ (Strength and Difficulties Questionnaire), and high reliability, the IRS is effective in describing features of social skill development.Conclusions: The IRS provides further evidence of the fact that in order to study children’s social skill development, it is important to evaluate various features of the caregiver-child interaction as a predictor of social skills

The relationship between the development of social competence and sleep in infants: a longitudinal study

BackgroundMany reports argue that sleep is important for children’s health, learning, and academic performance. The purpose of this longitudinal study was to examine the association between sleep and the development of social competence in infants.MethodsThis study was conducted as part of a Japan Science and Technology Agency (JST) project. Caregivers responded to the Japan Children’s Study Sleep Questionnaire when children were 18 months old. The interactions of caregivers and children were observed when children were 18, 30, and 42 months old, and rated with the Interaction Rating Scale, which is a measure of social competence.ResultsNocturnal sleep duration of more than 10 h and an earlier bed time than 22:00 were significantly correlated with two trajectory groups (low point and high point transition groups) of children’s social competence at 18, 30, and 42 months. Further, total sleep duration of more than 12.25 h and an earlier bed time than 22:00 were significantly correlated with the trajectory of children’s social competence at 18, 30, and 42 months.ConclusionsSleep duration and sleep onset time are important factors in children’s development of social competence

Colocalization of 14-3-3 Proteins with SOD1 in Lewy Body-Like Hyaline Inclusions in Familial Amyotrophic Lateral Sclerosis Cases and the Animal Model

Background and Purpose: Cu/Zn superoxide dismutase (SOD1) is a major component of Lewy body-like hyaline inclusion (LBHI) found in the postmortem tissue of SOD1-linked familial amyotrophic lateral sclerosis (FALS) patients. In our recent studies, 14-3-3 proteins have been found in the ubiquitinated inclusions inside the anterior horn cells of spinal cords with sporadic amyotrophic lateral sclerosis (ALS). To further investigate the role of 14-3-3 proteins in ALS, we performed immunohistochemical analysis of 14-3-3 proteins and compared their distributions with those of SOD1 in FALS patients and SOD1-overexpressing mice. Methods: We examined the postmortem brains and the spinal cords of three FALS cases (A4V SOD1 mutant). Transgenic mice expressing the G93A mutant human SOD1 (mutant SOD1-Tg mice), transgenic mice expressing the wild-type human SOD1 (wild-type SOD1-Tg mice), and non-Tg wild-type mice were also subjected to the immunohistochemical analysis. Results: In all the FALS patients, LBHIs were observed in the cytoplasm of the anterior horn cells, and these inclusions were immunopositive intensely for pan 14-3-3, 14-3-3$\beta$, and 14-3-3$\gamma$. In the mutant SOD1-Tg mice, a high degree of immunoreactivity for misfolded SOD1 (C4F6) was observed in the cytoplasm, with an even greater degree of immunoreactivity present in the cytoplasmic aggregates of the anterior horn cells in the lumbar spinal cord. Furthermore, we have found increased 14-3-3$\beta$ and 14-3-3$\gamma$ immunoreactivities in the mutant SOD1-Tg mice. Double immunofluorescent staining showed that C4F6 and 14-3-3 proteins were partially co-localized in the spinal cord with FALS and the mutant SOD1-Tg mice. In comparison, the wild-type SOD1-Tg and non-Tg wild-type mice showed no or faint immunoreactivity for C4F6 and 14-3-3 proteins (pan 14-3-3, 14-3-3$\beta$, and 14-3-3$\gamma$) in any neuronal compartments. Discussion: These results suggest that 14-3-3 proteins may be associated with the formation of SOD1-containing inclusions, in FALS patients and the mutant SOD1-Tg mice.Mathematic

LGI1–ADAM22–MAGUK configures transsynaptic nanoalignment for synaptic transmission and epilepsy prevention

Physiological functioning and homeostasis of the brain rely on finely tuned synaptic transmission, which involves nanoscale alignment between presynaptic neurotransmitter-release machinery and postsynaptic receptors. However, the molecular identity and physiological significance of transsynaptic nanoalignment remain incompletely understood. Here, we report that epilepsy gene products, a secreted protein LGI1 and its receptor ADAM22, govern transsynaptic nanoalignment to prevent epilepsy. We found that LGI1–ADAM22 instructs PSD-95 family membrane-associated guanylate kinases (MAGUKs) to organize transsynaptic protein networks, including NMDA/AMPA receptors, Kv1 channels, and LRRTM4–Neurexin adhesion molecules. Adam22ΔC5/ΔC5 knock-in mice devoid of the ADAM22–MAGUK interaction display lethal epilepsy of hippocampal origin, representing the mouse model for ADAM22-related epileptic encephalopathy. This model shows less-condensed PSD-95 nanodomains, disordered transsynaptic nanoalignment, and decreased excitatory synaptic transmission in the hippocampus. Strikingly, without ADAM22 binding, PSD-95 cannot potentiate AMPA receptor-mediated synaptic transmission. Furthermore, forced coexpression of ADAM22 and PSD-95 reconstitutes nano-condensates in nonneuronal cells. Collectively, this study reveals LGI1–ADAM22–MAGUK as an essential component of transsynaptic nanoarchitecture for precise synaptic transmission and epilepsy prevention