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1.
Proc Natl Acad Sci U S A ; 119(32): e2201578119, 2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35914156

RESUMO

Passive priming of prior knowledge to assimilate ongoing experiences underlies advanced cognitive processing. However, the necessary neural dynamics of memory assimilation remains elusive. Uninstructed brain could also show boosted creativity, particularly after idling states, yet it remains unclear whether the idling brain can spontaneously spark relevant knowledge assimilations. We established a paradigm that links/separates context-dependent memories according to geometrical similarities. Mice exploring one of four contexts 1 d before undergoing contextual fear conditioning in a square context showed a gradual fear transfer to preexposed geometrically relevant contexts the next day, but not after 15 min. Anterior cingulate cortex neurons representing relevant, rather than distinct, memories were significantly coreactivated during postconditioning sleep only, before their selective integration the next day during testing. Disrupting sleep coreactivations prevented assimilation while preserving recent memory consolidation. Thus, assimilating pertinent memories during sleep through coreactivation of their respective engrams represents the neural underpinnings of sleep-triggered implicit cortical learning.


Assuntos
Encéfalo , Aprendizagem , Consolidação da Memória , Sono , Animais , Encéfalo/fisiologia , Medo/fisiologia , Giro do Cíngulo/fisiologia , Memória , Consolidação da Memória/fisiologia , Camundongos
2.
J Obstet Gynaecol Res ; 49(3): 973-979, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36606606

RESUMO

AIM: To determine the impact of aromatase inhibitor (AI) use in oocyte cryopreservation among Japanese adolescent and young adult (AYA) cancer patients for fertility preservation, we evaluated the oocyte cryopreservation outcomes following AI therapy in combination with the follicular phase start (FPS) and random start (RS) protocols. METHODS: This retrospective study included 81 cycles of controlled ovarian stimulation (COS) among 73 AYA patients with cancer who underwent oocyte cryopreservation to maintain fertility. The outcome measures were the total number of matured oocytes that were retrieved and cryopreserved, as well as their maturation rates. The AI (+) and AI (-) groups were compared using the RS and FPS protocols. RESULTS: Our results showed that the combined use of AI and COS decreases serum E2 levels and maintains the number of retrieved and cryopreserved mature oocytes. We also confirmed the efficacy of the RS protocol, which was found to have comparable outcomes to that of the FPS protocol in both AI (+) and AI (-) groups. CONCLUSION: The combined use of AI and COS is beneficial for oocyte cryopreservation in patients with estrogen-sensitive cancer, regardless of the menstrual cycle phase of COS initiation.


Assuntos
Preservação da Fertilidade , Neoplasias , Feminino , Humanos , Inibidores da Aromatase , Recuperação de Oócitos/métodos , Estudos Retrospectivos , Criopreservação , Preservação da Fertilidade/métodos , Oócitos , Indução da Ovulação/métodos
3.
Nutr Health ; : 2601060221138644, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443993

RESUMO

BACKGROUND: Psychological characteristics of eating behaviour may be related to dietary habits. AIM: We investigated the association between eating behaviour characteristics and nutrition and food intake adequacy in Japanese adolescents. METHODS: This cross-sectional survey was conducted among 136 junior high school students (boys: 90, girls: 46) at a junior high school in Tokyo, Japan. Eating behaviour was categorised into three types (emotional, external, and restrained) using scores on the Japanese version of the Dutch Eating Behaviour Questionnaire. Dietary intake was assessed using a validated, brief self-administered diet history questionnaire. Inadequate nutrient intake was determined by counting the number of nutrients not meeting the dietary reference intake (DRI) for the Japanese population. The statistical analyses included Wilcoxon signed-rank tests, Spearman's rank correlation coefficient, and multiple regression analysis using JMP ver.14 (SAS Institute Inc., Cary, NC, USA). All reported p values are two-tailed, and p < 0.05 was regarded as statistically significant. RESULTS: Multiple regression analysis showed that restrained eating score was inversely associated with the number of nutrients not meeting the DRI (ß = - 0.28; p = 0.0027) and with total weight of snack intake (ß = - 0.30; p = 0.0010). Neither emotional nor external eating was significantly associated with the number of nutrients not meeting the DRI and with total weight of snack intake. CONCLUSIONS: These results suggest that adolescents with low restrained eating scores may have less self-control over their eating behaviour and may therefore have inadequate dietary intake.

4.
Exp Cell Res ; 364(2): 184-190, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29425714

RESUMO

Mammalian target of rapamycin (mTOR) signaling controls skeletal muscle cell differentiation, growth, and metabolism by sensing the intracellular energy status and nutrients. Recently, leucyl-tRNA synthetase (Lars) was identified as an intracellular sensor of leucine involved in the activation of mTOR signaling. However, there is still no evidence for the activation of mTOR signaling by Lars and its physiological roles in skeletal muscle cells. In this study, we determined the potential roles of Lars for the activation of mTOR signaling, skeletal muscle cell differentiation, hypertrophy, and metabolism using small interfering (si)-RNA knockdown. siRNA-mediated knockdown of Lars decreased phosphorylated p70 S6 kinase and inhibited the differentiation of C2C12 mouse myoblasts into myotubes, as evidenced by a decreased fusion index and decreased mRNA and protein expression levels of myogenic markers. Importantly, si-Lars decreased the level of Insulin-like growth factor 2 (Igf2) mRNA expression from the early stages of differentiation, indicating the possibility of an association between the mTOR-IGF2 axis and Lars. However, Lars knockdown did not decrease phosphorylated mTOR in differentiated myotubes, nor did it affect the hypertrophy of myotubes as evidenced by measuring their diameters and detecting the mRNA and protein expression of hypertrophy markers. Similarly, an extracellular flux analyzer showed that Lars knockdown did not affect the metabolism (glycolysis and mitochondrial respiration) of myotubes. These results demonstrate that Lars is required for skeletal muscle differentiation through the activation of mTOR signaling, but not for hypertrophy or metabolic alteration of myotubes.


Assuntos
Leucina-tRNA Ligase/metabolismo , Desenvolvimento Muscular , Fibras Musculares Esqueléticas/metabolismo , Mioblastos/citologia , Mioblastos/enzimologia , Animais , Células Cultivadas , Camundongos , Mioblastos/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
5.
Planta ; 247(3): 663-677, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29164368

RESUMO

MAIN CONCLUSION: Based on 3D sections through cells of Botryococcus braunii, the structure of three domains of endoplasmic reticulum, and their spatial and functional relationships to other organelles are clarified. Oil production by photosynthetic microalgae has attracted attention since these oils can be converted into renewable, carbon-neutral fuels. The green alga B. braunii accumulates large amounts of hydrocarbons, 30-50% of cell dry weight, in extracellular spaces rather than its cytoplasm. To advance the knowledge of hydrocarbon biosynthesis and transport pathways in this alga, we utilized transmission EM combined with rapid freezing and image reconstruction. We constructed detailed 3D maps distinguishing three ER domains: rdER with ribosomes on both sides, rsER with ribosomes on one side, and sER without ribosomes. The rsER and sER domains were especially prominent during the oil body formation and oil secretion stages. The ER contacted the chloroplasts, oil bodies, or plasma membrane via the rsER domains, oriented with the ribosome-free surface facing the organelles. We discuss the following transport pathway for hydrocarbons and their precursors in the cytoplasm: chloroplast â†’ endoplasmic reticulum (ER) â†’ oil bodies â†’ ER â†’ plasma membrane â†’ secretion. This study represents the first 3D study of the three-domain classification (rdER, rsER and sER) of the ER network among eukaryotic cells. Finally, we propose the novel features of the ERs in plant cells that are distinct from the latest proposed model for the ERs in mammalian cells.


Assuntos
Clorófitas/ultraestrutura , Retículo Endoplasmático/ultraestrutura , Hidrocarbonetos/metabolismo , Imageamento Tridimensional/métodos , Clorófitas/metabolismo , Retículo Endoplasmático/fisiologia , Microscopia Eletrônica , Microscopia de Fluorescência , Organelas/fisiologia , Organelas/ultraestrutura
6.
PLoS Biol ; 13(2): e1002070, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25723479

RESUMO

During sensory deprivation, the barrel cortex undergoes expansion of a functional column representing spared inputs (spared column), into the neighboring deprived columns (representing deprived inputs) which are in turn shrunk. As a result, the neurons in a deprived column simultaneously increase and decrease their responses to spared and deprived inputs, respectively. Previous studies revealed that dendritic spines are remodeled during this barrel map plasticity. Because cofilin1, a predominant regulator of actin filament turnover, governs both the expansion and shrinkage of the dendritic spine structure in vitro, it hypothetically regulates both responses in barrel map plasticity. However, this hypothesis remains untested. Using lentiviral vectors, we knocked down cofilin1 locally within layer 2/3 neurons in a deprived column. Cofilin1-knocked-down neurons were optogenetically labeled using channelrhodopsin-2, and electrophysiological recordings were targeted to these knocked-down neurons. We showed that cofilin1 knockdown impaired response increases to spared inputs but preserved response decreases to deprived inputs, indicating that cofilin1 dependency is dissociated in these two types of barrel map plasticity. To explore the structural basis of this dissociation, we then analyzed spine densities on deprived column dendritic branches, which were supposed to receive dense horizontal transcolumnar projections from the spared column. We found that spine number increased in a cofilin1-dependent manner selectively in the distal part of the supragranular layer, where most of the transcolumnar projections existed. Our findings suggest that cofilin1-mediated actin dynamics regulate functional map plasticity in an input-specific manner through the dendritic spine remodeling that occurs in the horizontal transcolumnar circuits. These new mechanistic insights into transcolumnar plasticity in adult rats may have a general significance for understanding reorganization of neocortical circuits that have more sophisticated columnar organization than the rodent neocortex, such as the primate neocortex.


Assuntos
Cofilina 1/genética , Espinhas Dendríticas/metabolismo , Neocórtex/metabolismo , Plasticidade Neuronal/fisiologia , Córtex Somatossensorial/metabolismo , Sinapses/metabolismo , Actinas/química , Actinas/genética , Actinas/metabolismo , Potenciais de Ação/fisiologia , Animais , Channelrhodopsins , Cofilina 1/antagonistas & inibidores , Cofilina 1/metabolismo , Espinhas Dendríticas/genética , Espinhas Dendríticas/ultraestrutura , Expressão Gênica , Técnicas de Silenciamento de Genes , Vetores Genéticos , Células HEK293 , Humanos , Lentivirus/genética , Lentivirus/metabolismo , Masculino , Neocórtex/ultraestrutura , Optogenética , Células PC12 , Ratos , Ratos Wistar , Privação Sensorial/fisiologia , Córtex Somatossensorial/ultraestrutura , Sinapses/genética , Sinapses/ultraestrutura
7.
Proc Natl Acad Sci U S A ; 111(10): E914-23, 2014 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-24567380

RESUMO

Radiation dose rates were evaluated in three areas neighboring a restricted area within a 20- to 50-km radius of the Fukushima Daiichi Nuclear Power Plant in August-September 2012 and projected to 2022 and 2062. Study participants wore personal dosimeters measuring external dose equivalents, almost entirely from deposited radionuclides (groundshine). External dose rate equivalents owing to the accident averaged 1.03, 2.75, and 1.66 mSv/y in the village of Kawauchi, the Tamano area of Soma, and the Haramachi area of Minamisoma, respectively. Internal dose rates estimated from dietary intake of radiocesium averaged 0.0058, 0.019, and 0.0088 mSv/y in Kawauchi, Tamano, and Haramachi, respectively. Dose rates from inhalation of resuspended radiocesium were lower than 0.001 mSv/y. In 2012, the average annual doses from radiocesium were close to the average background radiation exposure (2 mSv/y) in Japan. Accounting only for the physical decay of radiocesium, mean annual dose rates in 2022 were estimated as 0.31, 0.87, and 0.53 mSv/y in Kawauchi, Tamano, and Haramachi, respectively. The simple and conservative estimates are comparable with variations in the background dose, and unlikely to exceed the ordinary permissible dose rate (1 mSv/y) for the majority of the Fukushima population. Health risk assessment indicates that post-2012 doses will increase lifetime solid cancer, leukemia, and breast cancer incidences by 1.06%, 0.03% and 0.28% respectively, in Tamano. This assessment was derived from short-term observation with uncertainties and did not evaluate the first-year dose and radioiodine exposure. Nevertheless, this estimate provides perspective on the long-term radiation exposure levels in the three regions.


Assuntos
Radioisótopos de Césio/análise , Exposição Ambiental/análise , Acidente Nuclear de Fukushima , Neoplasias/epidemiologia , Doses de Radiação , Monitoramento de Radiação/estatística & dados numéricos , Previsões , Geografia , Humanos , Japão/epidemiologia , Fatores de Risco
8.
Rinsho Byori ; 64(2): 168-75, 2016 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-27311281

RESUMO

Clinical laboratory tests have been indispensable for medical services in recent years, and such a situation is associated with the offering of accurate test results by clinical laboratory units. A large number of facilities wishing to achieve ISO 15189 Certification follow preparatory procedures with support from consulting companies. However, in our facility, a limited budget did not allow us to use such services. As a solution, we participated in the Future Lab Session in OSAKA (FLS), a support group for the achievement of ISO 15189 Certification, when it was organized. Aiming to extensively cover and fulfill its responsibility for all processes, including clinical interpretations of the results obtained through patient preparation, in order to continuously offer high-quality test results to clinicians, our clinical laboratory unit underwent examination for certification, and consequently realized the necessity of third-party evaluation. The provision of laboratory services, fully complying with these standards, contributes to medical safety, in addition to accuracy improvement. Although the certification and its maintenance are costly, it is sufficiently cost-effective to achieve it, when focusing on improved efficiency and the enhanced quality and safety of medical services after work standardization.


Assuntos
Acreditação/normas , Serviços de Laboratório Clínico/normas , Melhoria de Qualidade , Qualidade da Assistência à Saúde/normas , Acreditação/economia , Serviços de Laboratório Clínico/economia , Análise Custo-Benefício
9.
Nihon Koshu Eisei Zasshi ; 62(2): 66-72, 2015.
Artigo em Japonês | MEDLINE | ID: mdl-25865402

RESUMO

OBJECTIVES: Interventions that promote physical activity to prevent psychological distress and disuse syndromes were carried out in disaster-stricken areas. However, the effect of these interventions to promote physical activity in disaster-stricken areas has not yet been fully clarified. The purpose of this study was to examine the health effects of promoting physical activity in a disaster-stricken area. METHODS: We conducted an exercise intervention as part of a health survey project among residents of Ishinomaki-city, Miyagi, Japan in 2012. To determine if changes in health condition differed between intervention participants and nonparticipants, health condition data from 81 participants were compared with data from 81 nonparticipants selected by propensity score matching. Factors including sex, age, original address (pre-quake), and six outcome variables (psychological distress [K6 score], subjective health status, sleep duration, sleep quality, frequency of outings, and time spent walking) were used for matching. A linear mixed model was used for statistical analysis. RESULTS: There were no significant differences in K6 score between participants and nonparticipants (P=0.913). Significant improvements were observed in subjective health status (P=0.011) and outing frequency (P=0.002), but not in other outcome variables. CONCLUSION: Subjective health status and outing frequency were significantly improved among participants of the exercise intervention. Exercise intervention may be an effective public health strategy in disaster-stricken areas.


Assuntos
Nível de Saúde , Atividade Motora , Adulto , Idoso , Idoso de 80 Anos ou mais , Terremotos , Feminino , Inquéritos Epidemiológicos , Humanos , Japão , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Sono , Estresse Psicológico
10.
Gan To Kagaku Ryoho ; 42(5): 525-8, 2015 May.
Artigo em Japonês | MEDLINE | ID: mdl-25981644

RESUMO

Numerous epidemiological studies, although not all, in Western countries have reported a possible differential impact of BMI on breast cancer risk in women of various lifestages. Among premenopausal women, a number of epidemiological studies in Western populations suggested a weak inverse association between BMI and breast cancer risk. Conversely, there exists substantial evidence for a statistically significant positive association between body weight and breast cancer risk among postmenopausal women. The cumulative exposure to estrogen throughout a woman's life is one of the significant risk factors for breast cancer. After menopause, adipose tissue is a major source of estrogen. Therefore, an increase in body fat after menopause is one of the possible explanations for the positive association of body weight with the development of breast cancer. To evaluate the impact of body weight on the risk of breast cancer, we need to consider the role of adipose tissue in the development and differentiation of normal mammary glands. Special attention should be paid to women in their twenties and/or during their lactation periods when the development of normal mammary glands is significant. Further studies are needed to investigate the association between BMI and breast cancer risk, considering the role of body fat in the development of mammary glands.


Assuntos
Neoplasias da Mama/etiologia , Obesidade/complicações , Magreza/etiologia , Peso Corporal , Feminino , Humanos , Glândulas Mamárias Humanas/crescimento & desenvolvimento , Pós-Menopausa , Pré-Menopausa , Fatores de Risco
11.
Congenit Anom (Kyoto) ; 64(2): 47-60, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38403785

RESUMO

Cranial neural crest cells (NCCs) are critical for craniofacial development. The administration of valproic acid (VPA) to pregnant females causes craniofacial malformations in offspring. However, the in vivo influence of VPA on mammalian cranial NCCs remains unclear. In this study, we aimed to elucidate the developmental stage-specific effect of VPA on cranial NCCs through the administration of a single dose of VPA to pregnant rat females immediately prior to the formation of the cranial neural crest (NC). We performed whole-mount immunohistochemistry or in situ hybridization to examine localization changes of gene transcripts associated with the epithelial-mesenchymal transition of the cranial NC (i.e., cranial NCC formation) and cranial NCC migration. The results showed that Hoxa2 mRNA was abnormally detected and Sox9 mRNA expression was decreased in the midbrain-rhombomere (R) 1/2 NC, which forms cranial NCCs that migrate to the frontonasal mass (FNM) and branchial arch (BA) 1, through VPA administration, thus reducing the formation of SNAI2-positive NCCs. Hoxa2-positive NCCs were detected normally in BA2 and abnormally in FNM and BA1, which are normally Hox-free, implying VPA-induced abnormal cranial NCC migration. In vitro verification experiments using the whole embryo culture system revealed that midbrain-R4 NCC migration was abnormal. These results indicate that VPA reduces the formation/delamination of the midbrain-R1/2 NCCs in a developmental stage-specific manner and subsequently causes the abnormal migration of R4 NCCs, which suggests that the abnormal formation and migration of cranial NCCs contribute to the inhibition of axonal elongation in the trigeminal nerve and a reduction in head size.


Assuntos
Crista Neural , Ácido Valproico , Animais , Ratos , Crista Neural/metabolismo , Ácido Valproico/toxicidade , RNA Mensageiro/metabolismo , RNA Mensageiro/farmacologia , Movimento Celular , Mamíferos
12.
Cancer Res Commun ; 4(2): 349-364, 2024 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-38284882

RESUMO

CD26 is ubiquitously and intensely expressed in osteoclasts in patients with multiple myeloma, whereas its expression in plasma cells of patients with multiple myeloma is heterogeneous because of its cellular diversity, immune escape, and disease progression. Decreased expression levels of CD26 in myeloma cells constitute one of the mechanisms underlying resistance to humanized anti-CD26 mAb therapy in multiple myeloma. In the current study, we show that histone deacetylase inhibition (HDACi) with broad or class-specific inhibitors involves the induction of CD26 expression on CD26neg myeloma cells both transcriptionally and translationally. Furthermore, dipeptidyl peptidase Ⅳ (DPPⅣ) enzymatic activity was concomitantly enhanced in myeloma cells. Combined treatment with HDACi plus CD26mAb synergistically facilitated lysis of CD26neg myeloma cells not only by antibody-dependent cellular cytotoxicity but also by the direct effects of mAb. Of note, its combination readily augmented lysis of CD26neg cell populations, refractory to CD26mAb or HDACi alone. Chromatin immunoprecipitation assay revealed that HDACi increased acetylation of histone 3 lysine 27 at the CD26 promoter of myeloma cells. Moreover, in the absence of HDACi, c-Myc was attached to the CD26 promoter via Sp1 on the proximal G-C box of myeloma cells, whereas, in the presence of HDACi, c-Myc was detached from Sp1 with increased acetylation of c-Myc on the promoter, leading to activation of the CD26 promoter and initiation of transcription in myeloma cells. Collectively, these results confirm that HDACi plays crucial roles not only through its anti-myeloma activity but by sensitizing CD26neg myeloma cells to CD26mAb via c-Myc/Sp1-mediated CD26 induction, thereby augmenting its cytotoxicity. SIGNIFICANCE: There is a desire to induce and sustain CD26 expression on multiple myeloma cells to elicit superior anti-myeloma response by humanized anti-CD26 mAb therapy. HDACi upregulates the expression levels of CD26 on myeloma cells via the increased acetylation of c-MycK323 on the CD26 promoter, leading to initiation of CD26 transcription, thereby synergistically augments the efficacy of CD26mAb against CD26neg myeloma cells.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Inibidores de Histona Desacetilases/farmacologia , Dipeptidil Peptidase 4/genética , Ácidos Hidroxâmicos/farmacologia , Histonas/metabolismo , Histona Desacetilases/genética
13.
Cell Death Discov ; 10(1): 302, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38914566

RESUMO

Despite the advances in the understanding of reproductive physiology, the mechanisms underlying ovarian aging are still not deciphered. Recent research found an association between impaired ATM-mediated DNA double-strand break (DSB) repair mechanisms and oocyte aging. However, direct evidence connecting ATM-mediated pathway function decline and impaired oocyte quality is lacking. The objective of this study was to determine the role of ATM-mediated DNA DSB repair in the maintenance of oocyte quality in a mouse oocyte knockdown model. Gene interference, in vitro culture, parthenogenesis coupled with genotoxicity assay approaches, as well as molecular cytogenetic analyses based upon next-generation sequencing, were used to test the hypothesis that intact ATM function is critical in the maintenance of oocyte quality. We found that ATM knockdown impaired oocyte quality, resulting in poor embryo development. ATM knockdown significantly lowered or blocked the progression of meiosis in vitro, as well as retarding and reducing embryo cleavage after parthenogenesis. After ATM knockdown, all embryos were of poor quality, and none reached the blastocyst stage. ATM knockdown was also associated with an increased aneuploidy rate compared to controls. Finally, ATM knockdown increased the sensitivity of the oocytes to a genotoxic active metabolite of cyclophosphamide, with increased formation of DNA DSBs, reduced survival, and earlier apoptotic death compared to controls. These findings suggest a key role for ATM in maintaining oocyte quality and resistance to genotoxic stress, and that the previously observed age-induced decline in oocyte ATM function may be a prime factor contributing to oocyte aging.

14.
Nat Commun ; 15(1): 4566, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914541

RESUMO

Idling brain activity has been proposed to facilitate inference, insight, and innovative problem-solving. However, it remains unclear how and when the idling brain can create novel ideas. Here, we show that cortical offline activity is both necessary and sufficient for building unlearned inferential knowledge from previously acquired information. In a transitive inference paradigm, male C57BL/6J mice gained the inference 1 day after, but not shortly after, complete training. Inhibiting the neuronal computations in the anterior cingulate cortex (ACC) during post-learning either non-rapid eye movement (NREM) or rapid eye movement (REM) sleep, but not wakefulness, disrupted the inference without affecting the learned knowledge. In vivo Ca2+ imaging suggests that NREM sleep organizes the scattered learned knowledge in a complete hierarchy, while REM sleep computes the inferential information from the organized hierarchy. Furthermore, after insufficient learning, artificial activation of medial entorhinal cortex-ACC dialog during only REM sleep created inferential knowledge. Collectively, our study provides a mechanistic insight on NREM and REM coordination in weaving inferential knowledge, thus highlighting the power of idling brain in cognitive flexibility.


Assuntos
Giro do Cíngulo , Aprendizagem , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal , Sono REM , Animais , Sono REM/fisiologia , Masculino , Córtex Pré-Frontal/fisiologia , Aprendizagem/fisiologia , Camundongos , Giro do Cíngulo/fisiologia , Vigília/fisiologia , Sono de Ondas Lentas/fisiologia , Conhecimento , Córtex Entorrinal/fisiologia , Neurônios/fisiologia
15.
J Neurosci ; 32(30): 10413-22, 2012 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-22836274

RESUMO

Many studies have reported the roles played by regulated proteolysis in synaptic plasticity and memory, but the role of autophagy in neurons remains unclear. In mammalian cells, autophagy functions in the clearance of long-lived proteins and organelles and in adaptation to starvation. In neurons, although autophagy-related proteins (ATGs) are highly expressed, autophagic activity markers, autophagosome (AP) number, and light chain protein 3-II (LC3-II) are low compared with other cell types. In contrast, conditional knock-out of ATG5 or ATG7 in mouse brain causes neurodegeneration and behavioral deficits. Therefore, this study aimed to test whether autophagy is especially regulated in neurons to adapt to brain functions. In cultured rat hippocampal neurons, we found that KCl depolarization transiently increased LC3-II and AP number, which was partially inhibited with APV, an NMDA receptor (NMDAR) inhibitor. Brief low-dose NMDA, a model of chemical long-term depression (chem-LTD), increased LC3-II with a time course coincident with Akt and mammalian target of rapamycin (mTOR) dephosphorylation and degradation of GluR1, an AMPA receptor (AMPAR) subunit. Downstream of NMDAR, the protein phosphatase 1 inhibitor okadaic acid, PTEN inhibitor bpV(HOpic), autophagy inhibitor wortmannin, and short hairpin RNA-mediated knockdown of ATG7 blocked chem-LTD-induced autophagy and partially recovered GluR1 levels. After chem-LTD, GFP-LC3 puncta increased in spines and in dendrites when AP-lysosome fusion was blocked. These results indicate that neuronal stimulation induces NMDAR-dependent autophagy through PI3K-Akt-mTOR pathway inhibition, which may function in AMPAR degradation, thus suggesting autophagy as a contributor to NMDAR-dependent synaptic plasticity and brain functions.


Assuntos
Autofagia/fisiologia , Hipocampo/metabolismo , Depressão Sináptica de Longo Prazo/fisiologia , Neurônios/metabolismo , Receptores de AMPA/metabolismo , Animais , Autofagia/efeitos dos fármacos , Células Cultivadas , Agonistas de Aminoácidos Excitatórios/farmacologia , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Depressão Sináptica de Longo Prazo/efeitos dos fármacos , Camundongos , N-Metilaspartato/farmacologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Serina-Treonina Quinases TOR/metabolismo
16.
Cancer Causes Control ; 24(12): 2117-28, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24091793

RESUMO

BACKGROUND: Epidemiological evidence for the impact of fruit and vegetable intake on breast cancer risk among the Japanese populations is scarce. OBJECTIVE: The purpose of this study was to evaluate the association between fruit and vegetable intake and breast cancer risk among 47,289 Japanese women. DESIGN: The study was conducted under a population-based prospective cohort design. Dietary assessment was performed using a validated food frequency questionnaire. A Cox proportional hazards regression model was used to calculate relative risks (RRs) and their corresponding 95 % confidence intervals (CIs). RESULTS: During an average of 10.2 years of follow-up, 452 cases of breast cancer were newly diagnosed. No association with breast cancer risk was seen for intake of total fruits and vegetables, cruciferous vegetables, green-leaf vegetables, yellow vegetables, or tomato products in overall or postmenopausal women. Cruciferous vegetable intake was associated with a statistically significant decrease in risk of premenopausal breast cancer [multivariable-RRQ4 vs. Q1 = 0.64 (95 % CI = 0.38-1.10; p trend = .046)] and showed a marginally inverse association with ER+ PR+ tumors [RRper 100 g increment = 0.64 (95 % CI = 0.41-1.00)]. In contrast, positive associations were seen between intake of total fruits and citrus fruits and breast cancer risk in overall and premenopausal women. However, these associations for fruit were all attenuated with additional adjustment for vitamin C intake. CONCLUSIONS: Our results suggest an overall null association between total fruit and vegetable intake and breast cancer risk. Intake of cruciferous vegetable showed a statistically significant association with a decreased risk of breast cancer among premenopausal women.


Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/metabolismo , Comportamento Alimentar , Frutas , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Verduras , Adulto , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
17.
Rinsho Byori ; 61(5): 375-81, 2013 May.
Artigo em Japonês | MEDLINE | ID: mdl-23947174

RESUMO

The mortality among patients with heart diseases increases steadily in an aging society like Japan. Among those, the patients with chronic heart failure (CHF) are thought to be increasing rapidly although the official report is missing. It is well-known that BNP or NT-proBNP is useful for a clinical diagnosis of CHF, but a role of the cardiac troponin (cTn) attracts attention as a novel biomarker of their prognosis. However, because the level of cTn in patients with CHF is far lower than that in cases of acute coronary syndrome (ACS), development of the high-sensitive method with precision is desired. In the present study, a new sensitive assay system with an analyzer, ARCHITECT STAT (cTnI hs-ARCH) was basically studied and found more sensitive than other conventional 2 sensitive methods. The performance of cTnI hs-ARCH was evaluated in patients with CHF by comparing it to findings with other 2 methods. When CHF patients are allocated into categories of NYHA classification according to their subjective symptoms, cTnI hs-ARCH was superior to other methods in discriminating subgroups. In addition, multivariable analysis disclosed that cTnI hs-ARCH is influenced by the level of renal function at the minimum among the 3 methods. Therefore, cTnI hs-ARCH may be a useful method for evaluation of prognosis in patients with CHF who often have impaired renal function.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Insuficiência Cardíaca/diagnóstico , Infarto do Miocárdio/diagnóstico , Troponina I/sangue , Biomarcadores/sangue , Doença Crônica , Feminino , Humanos , Masculino , Sensibilidade e Especificidade
18.
AIMS Public Health ; 10(1): 52-62, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37063363

RESUMO

Background: The contents of children's daily activities and the amount of time spent on them has been directly linked to their health and development. Parental health behavior has also been considered a key factor, and the aim of this study was to determine the relationship between parent/guardian health literacy (HL) and their child's time spent at home by behavioral types. The study was conducted in elementary schools in Japan. Method: The target subjects for this study were elementary schoolchildren (all grades, aged 6 to 12 years) and their parents/guardians, and almost 3000 schoolchildren and their parents/guardians in the Northern and Southern districts in Japan participated. The questionnaire for parents/guardians included amount of time spent per day on the seven major behavioral contents of their child's time at home, on weekdays and weekends, respectively, and a shortened five-item health literacy (HL) scale. Parent/guardian HL results were categorized into two groups (low HL group and high HL group), and we analyzed the association between the HL and child's time spent at home by behavioral contents. Results: Children in the high HL parent/guardian group spent significantly less time watching TV and playing games than those in the low HL group, both on weekdays and weekends. Time spent playing outside on weekdays and on hobbies on weekdays and weekends was significantly longer for children in the high HL parent/guardian group than in the low HL group. Results of logistic regression analyses adjusted for confounders showed that higher parental/guardian HL reduced children's spending more than 30 minutes watching TV or playing games and increased children's spending more than 30 minutes on outside playing and doing hobbies. Conclusions: Parental/guardian HL affected the child's time spent at home. The results could suggest that increasing parental/guardian HL has strong potential to improve children's major lifestyle behaviors..

19.
J Electron Microsc (Tokyo) ; 61(5): 309-20, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22802488

RESUMO

This study aimed at elucidating whether estrogen deficiency would affect the synthesis of an osteocyte-derived factor, sclerostin, in the mesial region of alveolar bone. Eight 9-week-old Wistar female rats were ovariectomized (OVX) and eight other rats were Sham-operated (Sham). After 4 weeks, the interradicular septa of mandibular first molar were embedded in paraffin and then histochemically examined. Sclerostin-positive osteocytes were located in the superficial layer of the mesial region of Sham bones, whereas the OVX mesial region showed less sclerostin-reactive osteocytes. There was no significant difference in the distribution of estrogen receptor α and terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling -positive cells in the groups studied. The Sham mesial region featured many osteoclasts, and OVX specimens showed numerous osteoclasts in association with intense immunolabeling of the receptor activator of the nuclear factor kB ligand. Contrary to the observations in Sham specimens, a complex meshwork of cement lines was seen in the OVX mesial region, accompanied by an irregularly distributed osteocytic lacunar-canalicular system. In conclusion, estrogen deficiency appears to inhibit osteocyte-derived sclerostin synthesis in the mesial region of the interradicular septum, in a process that seems to be mediated by accelerated bone remodeling rather than by direct effects on osteocytes.


Assuntos
Proteínas Morfogenéticas Ósseas/biossíntese , Remodelação Óssea/efeitos dos fármacos , Osteoclastos/metabolismo , Osteócitos/efeitos dos fármacos , Osteócitos/metabolismo , Fosfatase Ácida/metabolismo , Animais , Proteínas Morfogenéticas Ósseas/genética , Osso e Ossos/metabolismo , Catepsina K/genética , Catepsina K/metabolismo , Estrogênios/deficiência , Estrogênios/farmacologia , Feminino , Marcadores Genéticos/genética , Marcação In Situ das Extremidades Cortadas , Isoenzimas/metabolismo , Ovariectomia , Ratos , Ratos Wistar , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Fosfatase Ácida Resistente a Tartarato , Receptor ERRalfa Relacionado ao Estrogênio
20.
Rinsho Byori ; 60(5): 407-13, 2012 May.
Artigo em Japonês | MEDLINE | ID: mdl-22774568

RESUMO

In the present study, we evaluated the performance and clinical utility of a high-sensitivity troponin T (hs-cTnT) assay. The within- and between-assay variations (coefficients of variation: CV) in the low and high concentrations of troponin T in serum samples were 0.84% to 3.34%, respectively. Analysis of interferents showed that only hemoglobin negatively influenced the assay results. Blank assay was < 0.001 ng/mL, and a limit of quantification (10% CV) was found at 0.005 ng/mL. The correlation coefficient (r) between hs-cTnT and the conventional assay was 0.997 (p < 0.000). The high-sensitivity assay system could detect cTnT in 88% of samples in which the conventional assay could not detect any immunoreactivity. The 99th percentile in healthy subjects, determined using 559 samples from medical checkups, was 0.011 ng/mL. There was a gender difference (hs-cTnT levels were higher in men than in women), and hs-cTnT levels increased with age. Because hs-cTnT level exceeded 0.011 ng/mL approximately 2 hours after the onset of chest pain in patients with acute myocardial infarction, hs-cTnT can serve as a biomarker for early detection of myocardial infarction. There was a positive correlation (r = 0.491, p < 0.001) between hs-cTnT and NT-proBNP, and hs-cTnT levels increased with the progression of the disease state, as assessed using New York Heart Association (NYHA) classification. These findings indicate that the hs-cTnT assay is sensitive enough to diagnose early-stage acute myocardial infarction and congestive heart failure.


Assuntos
Imunoensaio/métodos , Medições Luminescentes/métodos , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Troponina T/sangue , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
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