RESUMEN
Histone deacetylase 6 (HDAC6) is known to deacetylate amino acid lysine in alpha-tubulin. However, the functional role of HDAC6 in the progression of cardiac disease remains uncertain. The functional role of HDAC6 in the hearts was examined using transgenic (TG) mice expressing either human wild-type HDAC6, deacetylase inactive HDAC6 (HDAC6H216A, H611A), and human HDAC6 replaced all serine or threonine residues with aspartic acid at N-terminal 1- 43 amino acids (HDAC6NT-allD) specifically in the hearts. Overexpression of wild-type HDAC6 significantly reduced acetylated tubulin levels, and overexpression of HDAC6H216A, H611A significantly increased it in the mouse hearts. Detectable acetylated tubulin disappeared in HDAC6NT-allD TG mouse hearts. Neither histological alteration nor alteration of cardiac function was observed in the HDAC6 TG mouse hearts. To analyze the role of HDAC6 and acetylated tubulin in disease conditions, we examined HDAC6 in isoprenaline-induced hypertrophy or pressure-overload hypertrophy (TAC). No obvious alteration in the heart weight/body weight ratio or gene expressions of hypertrophic markers between NTG and HDAC6NT-allD mice was observed following treatment with isoprenaline. In contrast, a marked reduction in the shortening fraction and dilated chamber dilatation was detected in the HDAC6NT-allD TG mouse hearts 2 weeks after TAC. A sustained low level of acetylated tubulin and acetylated cortactin was observed in the TAC HDAC6NT-allD TG mouse hearts. Cardiac HDAC6 activity that can regulate acetylated levels of tubulin and cortactin may be critical factors involved in cardiac disease such as pressure-overload hypertrophy.
Asunto(s)
Cardiopatías , Histona Desacetilasa 6/metabolismo , Tubulina (Proteína) , Acetilación , Animales , Ácido Aspártico/metabolismo , Cortactina/metabolismo , Histona Desacetilasa 6/genética , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Humanos , Hipertrofia , Isoproterenol , Lisina/metabolismo , Ratones , Ratones Transgénicos , Serina/metabolismo , Treonina/metabolismo , Tubulina (Proteína)/metabolismoRESUMEN
BACKGROUND: School teachers have a possibility toward at-risk Internet addiction (IA) due to increased opportunities to use the Internet, along with the spread of the Internet in recent years. Burnout syndrome (BOS) is found to be one of the symptoms related to unhealthy mental health, especially among teachers. This study aims to research the relationship between at-risk IA and the Internet usage or BOS by conducting a nationwide cross-sectional survey and examining the factors associated with IA. METHOD: This study was a cross-sectional survey by anonymous questionnaire. This survey was a random sampling survey of junior high schools across Japan in 2016. The participants were 1696 teachers at 73 schools (response rate in teachers 51.0%). We asked participants for details of their backgrounds, Internet usage, the Internet Addiction Test (IAT) by Young, and the Japanese Burnout Scale (JBS). We divided the participants into either the at-risk IA group (IAT score ⧠40, n = 96) or the non-IA group (IAT score < 40, n = 1600). To compare the difference between at-risk IA and non-IA, we used nonparametric tests and t test according to variables. To analyze the relationship between the IAT score and the scores of three factors of the JBS (emotional exhaustion, depersonalization, and personal accomplishment), we used both ANOVA and ANCOVA, adjusted by relevant confounding factors. To clarify the contribution of each independent variable to IAT scores, we used multiple logistic regression analysis. RESULTS: In our study, at-risk IA was associated with using the internet many hours privately, being on the Internet both on weekdays and weekends, playing games, and surfing the Internet. In the relationship between IAT score and BOS factor score, a higher score for "depersonalization" had a positive relationship with at-risk IA, and the highest quartile for "decline of personal accomplishment" had a lower odds ratio with at-risk IA by multiple logistic regression analysis. CONCLUSION: We clarified there is a significant relationship between at-risk IA and BOS among junior high school teachers in a nationwide survey. Our results suggest that finding depersonalization at the early stage may lead to the prevention of at-risk IA among teachers. Those who are at-risk of IA may feel personal accomplishment through use of the Internet.
Asunto(s)
Conducta Adictiva/psicología , Agotamiento Psicológico/psicología , Internet , Satisfacción Personal , Maestros/psicología , Adulto , Análisis de Varianza , Estudios Transversales , Humanos , Japón , Masculino , Persona de Mediana Edad , Factores de Riesgo , Instituciones Académicas , Encuestas y CuestionariosRESUMEN
Bcl-2-associated athanogene 3 (BAG3) is strongly expressed in both cardiac and skeletal muscle. A recent study showed that BAG3 may play a protective role in muscles. Little is known, however, regarding the detailed role of BAG3 in cardiac muscle. To better understand the functional role of cardiac BAG3 in the heart, we generated transgenic (TG) mice that overexpress BAG3. A decrease in fractional shortening, and the induction of cardiac atrial natriuretic peptide, were observed in BAG3 TG mice. Moreover, a marked reduction in the protein level of small HSPs was detected in BAG3 TG mouse hearts. We analyzed the cardiac small HSP levels when either the ubiquitin-proteasome system (UPS) or the autophagy system (AS) was inhibited in BAG3 TG mice. The protein turnovers of small HSPs by the AS were activated in BAG3 TG mouse hearts. Thus, BAG3 is critical for the protein turnover of small HSPs via activation of autophagy in the heart.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Autofagia/fisiología , Proteínas de Choque Térmico Pequeñas/metabolismo , Miocardio/citología , Miocardio/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Proteínas Reguladoras de la Apoptosis/genética , Masculino , Tasa de Depuración Metabólica , Ratones , Ratones Endogámicos C57BL , Ratones TransgénicosRESUMEN
BACKGROUND: The prevalence of Internet addiction (IA) among employed adults has not been reported using a large sample. To clarify the actual status of addictive Internet use among employed adults, this study aimed to evaluate the prevalence and the risk factors of IA and at-risk IA among employed adults in Japan. METHODS: This cross-sectional study surveyed all junior and senior high school personnel in Shimane Prefecture, a rural area in Japan. Eligible participants included 3,211 junior and senior high school personnel (1,259 men and 1,952 women). Participants completed a questionnaire on their activities and factors related to Internet use. RESULTS: The prevalence of IA and at-risk IA was 0.03% and 4.82%, respectively. Furthermore, game playing was shown to be the Internet activity most closely associated with at-risk IA. CONCLUSIONS: This study showed that around 5% of school personnel in a rural area in Japan are at risk for developing addiction to the Internet and that using the Internet for game playing is related to at-risk IA. Our results suggest that employed adults should be instructed to use the Internet properly.
Asunto(s)
Conducta Adictiva/epidemiología , Empleo/estadística & datos numéricos , Internet , Adulto , Estudios Transversales , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Población Rural/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
In an embryonic developmental stage of the peripheral nervous system (PNS), Schwann cell precursors migrate along neuronal axons to their final destinations. After birth, they eventually wrap around individual axons to form myelin sheaths, which insulate axons to increase the nerve conduction velocity. Some growth factors and adhesion molecules are known to control these developmental stages from in the fish to in the mammal. Neuregulin-1 (NRG1), which is composed of many alternative splicing variants, is such a growth factor. Among these variants, the type III isoform of NRG1, interacting with ErbB2 and ErbB3 receptors on Schwann cells, plays an essential role in myelination in the fish and the mammal. NRG1 type III is also known to promote migration of fish Schwann cell precursors; however, it still remains to be clarified whether mammalian type III isoform does it. We have therefore generated type III isoform-specific knockout mice in inbred strain. The mice result in delayed migration of the precursors from the dorsal to ventral root via a peripheral ganglion, comparing littermate controls. Similar results are observed in an in vitro migration assay using reaggregated Schwann cell precursors. Furthermore, the knockout mice exhibit reduced myelin thickness, consistent with the established role of NRG1 type III in myelination. These results indicate that in mice, NRG1 type III plays a key role not only in myelination but also in migration.
Asunto(s)
Vaina de Mielina/genética , Neurregulina-1/metabolismo , Receptor ErbB-2/metabolismo , Receptor ErbB-3/metabolismo , Células de Schwann/metabolismo , Médula Espinal/metabolismo , Animales , Diferenciación Celular , Movimiento Celular , Expresión Génica , Ratones , Ratones Noqueados , Vaina de Mielina/metabolismo , Vaina de Mielina/patología , Neurregulina-1/genética , Ratas , Ratas Sprague-Dawley , Receptor ErbB-2/genética , Receptor ErbB-3/genética , Células de Schwann/patología , Transducción de Señal , Médula Espinal/patologíaRESUMEN
During development of the peripheral nervous system (PNS), Schwann cells wrap neuronal axons, becoming the myelin sheaths that help axonal functions. While the intercellular signals controlling the myelination process between Schwann cells and peripheral neurons are well studied, the transduction of these signals in Schwann cells still remains elusive. Here, we show that Arf6, an Arf protein of the small GTPase family, is involved in promoting the myelination process. Knockdown of Arf6 with the small-interfering (si)RNA in primary Schwann cells markedly decreases dibutyl-cyclic AMP-induced myelin marker protein expression, indicating that Arf6 plays a role in differentiation-like phenotypic changes. To obtain in vivo evidence, we generated small-hairpin (sh)RNA transgenic mice targeting Arf6 for Schwann cells. Transgenic mice exhibited reduced myelin thickness compared to littermate controls, consistent with the defective myelin formation observed in the transgenic mouse-derived Schwann cell and neuronal culture system. Transgenic mice also exhibited decreased phosphorylation of myelination-related signaling molecules such as Akt kinase cascade proteins as well as downregulation of myelin marker proteins. These results suggest that signaling through Arf6 is required for Schwann cell myelination, adding Arf6 to the list of intracellular signaling molecules involved in the myelination process.
Asunto(s)
Factores de Ribosilacion-ADP/metabolismo , Diferenciación Celular/fisiología , Vaina de Mielina/fisiología , Neurogénesis/fisiología , Células de Schwann/citología , Células de Schwann/metabolismo , Factor 6 de Ribosilación del ADP , Animales , Células Cultivadas , Femenino , Técnicas de Silenciamiento del Gen , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Ratas , Ratas Sprague-Dawley , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Sensori-perceptual processing of emotional stimuli under attentive conditions effectively prevents response disinhibition. This is observed saliently in low-impulsive people, because of their high sensitivity to warning signals, such as emotional faces. Results from human neurophysiological studies have been used to develop a dual detector model for early sensori-perceptual processing. A transient detector mechanism is related to automatic neurophysiological arousal in response to warning signals, which is reflected by early frontal event-related potential effects. The memory-based detector mechanism is associated with subsequent mismatch negativity (MMN), which reflects a short-term memory trace of signals. Based on previous findings, we predicted that impulsivity affects functional associations among the dual detector mechanisms, and modulates early frontal and/or MMN activities. In the present study, we recorded electroencephalograms for twenty-one healthy adults using a visual oddball paradigm with neutral faces as frequent stimuli, and angry and happy faces as infrequent stimuli. We measured the impulsivity traits by a self-report scale (the Barratt Impulsiveness Scale, 11th version). RESULTS: Main findings were that only happy faces increased early frontal negativity and subsequent occipital visual MMN (vMMN) for emotional change, and these neurophysiological effects positively correlated with each other in a temporally causal manner. However, an impulsivity sub-trait positively correlated selectively with vMMN for the happy faces. CONCLUSION: These findings demonstrate that higher impulsivity is associated with attenuated vMMN for emotional change detection in healthy populations, potentially because of weakened fronto-occipital functional connection that is responsible for the dual detector mechanism.
Asunto(s)
Encéfalo/fisiología , Reconocimiento Facial/fisiología , Conducta Impulsiva/fisiología , Personalidad/fisiología , Adulto , Electroencefalografía , Emociones , Potenciales Evocados , Expresión Facial , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Pruebas de Personalidad , Tiempo de Reacción , AutoinformeRESUMEN
A K141N missense mutation in heat shock protein (HSP) B8, which belongs to the small HSP family, causes distal hereditary motor neuropathy, which is characterized by the formation of inclusion bodies in cells. Although the HSPB8 gene causes hereditary motor neuropathy, obvious expression of HSPB8 is also observed in other tissues, such as the heart. The effects of a single mutation in HSPB8 upon the heart were analyzed using rat neonatal cardiomyocytes. Expression of HSPB8 K141N by adenoviral infection resulted in increased HSPB8-positive aggregates around nuclei, whereas no aggregates were observed in myocytes expressing wild-type HSPB8. HSPB8-positive aggresomes contained amyloid oligomer intermediates that were detected by a specific anti-oligomer antibody (A11). Expression of HSPB8 K141N induced slight cellular toxicity. Recombinant HSPB8 K141N protein showed reactivity against the anti-oligomer antibody, and reactivity of the mutant HSPB8 protein was much higher than that of wild-type HSPB8 protein. To extend our in vitro study, cardiac-specific HSPB8 K141N transgenic (TG) mice were generated. Echocardiography revealed that the HSPB8 K141N TG mice exhibited mild hypertrophy and apical fibrosis as well as slightly reduced cardiac function, although no phenotype was detected in wild-type HSPB8 TG mice. A single point mutation of HSPB8, such as K141N, can cause cardiac disease.
Asunto(s)
Cardiomiopatías/metabolismo , Proteínas del Choque Térmico HSP20/genética , Proteínas del Choque Térmico HSP20/fisiología , Proteínas de Choque Térmico/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/fisiología , Animales , Cardiomiopatías/genética , Citosol/metabolismo , ADN Complementario/metabolismo , Fibrosis/patología , Inmunohistoquímica/métodos , Ratones , Ratones Transgénicos , Mitocondrias/metabolismo , Chaperonas Moleculares , Mutación , Mutación Missense , Fenotipo , Mutación Puntual , Ratas , Proteínas Recombinantes/metabolismoRESUMEN
The myelin sheath insulates neuronal axons and markedly increases the nerve conduction velocity. In the peripheral nervous system (PNS), Schwann cell precursors migrate along embryonic neuronal axons to their final destinations, where they eventually wrap around individual axons to form the myelin sheath after birth. ErbB2 and ErbB3 tyrosine kinase receptors form a heterodimer and are extensively expressed in Schwann lineage cells. ErbB2/3 is thought to be one of the primary regulators controlling the entire Schwann cell development. ErbB3 is the bona fide Schwann cell receptor for the neuronal ligand neuregulin-1. Although ErbB2/3 is well known to regulate both Schwann cell precursor migration and myelination by Schwann cells in fishes, it still remains unclear whether in mammals, ErbB2/3 actually regulates Schwann cell precursor migration. Here, we show that knockdown of ErbB3 using a Schwann cell-specific promoter in mice causes delayed migration of Schwann cell precursors. In contrast, littermate control mice display normal migration. Similar results are seen in an in vitro migration assay using reaggregated Schwann cell precursors. Also, ErbB3 knockdown in mice reduces myelin thickness in sciatic nerves, consistent with the established role of ErbB3 in myelination. Thus, ErbB3 plays a key role in migration, as well as in myelination, in mouse Schwann lineage cells, presenting a genetically conservative role of ErbB3 in Schwann cell precursor migration.
Asunto(s)
Movimiento Celular/genética , Regulación del Desarrollo de la Expresión Génica , Neurogénesis/genética , Receptor ErbB-3/genética , Células de Schwann/metabolismo , Animales , Axones/metabolismo , Axones/ultraestructura , Diferenciación Celular , Embrión de Mamíferos , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Vaina de Mielina/metabolismo , Vaina de Mielina/ultraestructura , Neurregulina-1/genética , Neurregulina-1/metabolismo , Regiones Promotoras Genéticas , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-3/antagonistas & inhibidores , Receptor ErbB-3/metabolismo , Células de Schwann/ultraestructura , Nervio Ciático/crecimiento & desarrollo , Nervio Ciático/metabolismo , Nervio Ciático/ultraestructura , Transducción de SeñalRESUMEN
CD4(+) T cell activation is controlled by signaling through the T cell receptor in addition to various co-receptors, and is also affected by their interactions with effector and regulatory T cells in the microenvironment. Inflammatory bowel diseases (IBD) are caused by the persistent activation and expansion of auto-aggressive CD4(+) T cells that attack intestinal epithelial cells. However, the molecular basis for the persistent activation of CD4(+) T cells in IBD remains unclear. In this study, we investigated how the CD98 heavy chain (CD98hc, Slc3a2) affected the development of colitis in an experimental animal model. Transferring CD98hc-deficient CD4(+)CD25(-) T cells into Rag2(-/-) mice did not cause colitis accompanied by increasing Foxp3(+) inducible regulatory T cells. By comparison, CD98hc-deficient naturally occurring regulatory T cells (nTregs) had a decreased capability to suppress colitis induced by CD4(+)CD25(-) T cells, although CD98hc-deficient mice did not have a defect in the development of nTregs. Blocking CD98hc with an anti-CD98 blocking antibody prevented the development of colitis. Our results indicate that CD98hc regulates the expansion of autoimmune CD4(+) T cells in addition to controlling nTregs functions, which suggests the CD98hc as an important target molecule for establishing strategies for treating colitis.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Colitis/inmunología , Colitis/patología , Colon/patología , Cadena Pesada de la Proteína-1 Reguladora de Fusión/inmunología , Animales , Enfermedades Autoinmunes/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/patología , Colitis/genética , Colon/inmunología , Colon/metabolismo , Proteínas de Unión al ADN/genética , Cadena Pesada de la Proteína-1 Reguladora de Fusión/genética , Eliminación de Gen , Subunidad alfa del Receptor de Interleucina-2/genética , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BLRESUMEN
In CBA/J and C3H/HeJ mice, retinitis pigmentosa is inherited as an autosomal-recessive trait due to a mutation in Pde6b, which encodes cGMP phosphodiesterase subunit b. In these strains, the Y347X mutation in Pde6b leads to the upregulation of cGMP levels, increased Ca2+ influx induces rod death, and the outer segment and rod cells entirely disappeared by 35 days after birth. In the present study, we utilized the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) 9-mediated gene editing to repair the Y347X mutation in CBA/J and C3H/HeJ mice. Evaluation of the established CBA/J-Pde6bY347Y/Y347X and C3H/HeJ-Pde6bY347Y/Y347X mice, which were confirmed to have normal retinal layers by live fundoscopic imaging and histopathological analysis, revealed improved visual acuity based on the visual cliff and light/dark latency tests. Furthermore, our analyses revealed that the visible platform test was a more effective tool for testing visual behavior in these mice. The results suggest that the established strains can serve as control groups for CBA/J and C3H/HeJ in ophthalmology studies involving retinitis pigmentosa.
Asunto(s)
Fosfodiesterasas de Nucleótidos Cíclicos Tipo 6 , Ratones Endogámicos C3H , Ratones Endogámicos CBA , Animales , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 6/genética , Retinitis Pigmentosa/genética , Ratones , Edición Génica , Mutación , Modelos Animales de Enfermedad , Agudeza Visual/fisiología , Sistemas CRISPR-Cas , Retina/metabolismoRESUMEN
Rapid eating has been demonstrated to be associated with obesity and overweight. However, few studies have characterized the separate relationships of eating speed with visceral and subcutaneous fat mass or circulating adiponectin concentration. We hypothesized that rapid eating is associated with the larger visceral fat tissue (VFT) area and lower adiponectin concentration, but not with the subcutaneous fat tissue (SFT) area in men and women. We performed a cross-sectional study of 712 adults aged 20-86 years (528 men and 184 women; mean ± SD age 59.36 ± 13.61 years). The participants completed a self-reported questionnaire, and underwent anthropometric and laboratory measurements and computed tomographic imaging of the abdomen as a part of annual medical check-ups. Multivariate linear regression analyses revealed that rapid eating was associated with larger visceral (B = 24.74; 95% CI 8.87-40.61, p = 0.002) and subcutaneous fat areas (B = 31.31; 95% CI 12.23-50.38, p = 0.001), lower adiponectin concentration (B = - 2.92; 95% CI - 4.39- - 1.46, p < 0.001), higher body mass index (BMI) (B = 2.13; 95% CI 1.02-3.25, p < 0.001), and larger waist circumference (B = 5.23; 95% CI 2.16-8.30, p < 0.001) in men, which is partially consistent with the hypothesis. In contrast, rapid eating was found to be associated only with BMI, and not with abdominal adipose area or adiponectin concentration in women, which is a result that is not consistent with the hypothesis. These results suggest that there is no difference in the association of rapid eating with VFT and SFT areas.
Asunto(s)
Adiponectina , Obesidad , Adulto , Masculino , Humanos , Femenino , Estudios Transversales , Índice de Masa Corporal , Grasa Subcutánea/diagnóstico por imagen , Grasa Intraabdominal/diagnóstico por imagenRESUMEN
BACKGROUND: Internet addiction (IA) has been drawing attention to mental health. However, few reports have been found on the related factors of at-risk IA among regular workers by a nationwide survey. The study aimed to evaluate the characteristics of at-risk IA and identify related factors among senior high school teachers in Japan. METHODS: This survey was a cross-sectional survey of high schools across Japan in 2017. There were 3189 teachers (2088 males and 1098 female) who participated in this survey. The questionnaire asked about their devices, both the time and the activities of using their internet, and sociodemographic factors. IA was measured by the internet addiction test (IAT) by which 40-79 points were classified as at-risk IA, and more as IA. We compared the related factors of at-risk IA and non-IA using descriptive analysis and multivariable regression analysis. RESULTS: The rates of IA and at-risk IA were 0.09% (n = 3) and 6.91% (n = 220), respectively. At-risk IA was positively associated with activities on the internet for gaming, entertainment, net-surfing, and younger ages. In addition, the at-risk IA group had a longer time spent on the internet than the non-IA group. CONCLUSIONS: Around 7% of high school teachers are at-risk IA in this survey, though they have regular work. Our results suggest that at-risk IA may be reinforced not only by the active internet use such as gaming, but also by purposeless behaviors, such as net-surfing. Managing time on the internet may support preventing at-risk IA among senior high school teachers.
Asunto(s)
Conducta Adictiva , Maestros , Masculino , Humanos , Femenino , Japón/epidemiología , Estudios Transversales , Trastorno de Adicción a Internet , Conducta Adictiva/epidemiología , Prevalencia , Encuestas y CuestionariosRESUMEN
In development of the peripheral nervous system, Schwann cells proliferate, migrate, and ultimately differentiate to form myelin sheath. In all of the myelination stages, Schwann cells continuously undergo morphological changes; however, little is known about their underlying molecular mechanisms. We previously cloned the dock7 gene encoding the atypical Rho family guanine-nucleotide exchange factor (GEF) and reported the positive role of Dock7, the target Rho GTPases Rac/Cdc42, and the downstream c-Jun N-terminal kinase in Schwann cell migration (Yamauchi et al., 2008). We investigated the role of Dock7 in Schwann cell differentiation and myelination. Knockdown of Dock7 by the specific small interfering (si)RNA in primary Schwann cells promotes dibutyryl cAMP-induced morphological differentiation, indicating the negative role of Dock7 in Schwann cell differentiation. It also results in a shorter duration of activation of Rac/Cdc42 and JNK, which is the negative regulator of myelination, and the earlier activation of Rho and Rho-kinase, which is the positive regulator of myelination. To obtain the in vivo evidence, we generated Dock7 short hairpin (sh)RNA transgenic mice. They exhibited a decreased expression of Dock7 in the sciatic nerves and enhanced myelin thickness, consistent with in vitro observation. The effects of the in vivo knockdown on the signals to Rho GTPases are similar to those of the in vitro knockdown. Collectively, the signaling through Dock7 negatively regulates Schwann cell differentiation and the onset of myelination, demonstrating the unexpected role of Dock7 in the interplay between Schwann cell migration and myelination.
Asunto(s)
Diferenciación Celular/fisiología , Regulación del Desarrollo de la Expresión Génica/fisiología , Factores de Intercambio de Guanina Nucleótido/metabolismo , Vaina de Mielina/metabolismo , Células de Schwann/fisiología , Animales , Animales Recién Nacidos , Bucladesina/farmacología , Diferenciación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Células Cultivadas , Embrión de Mamíferos , Femenino , Proteínas Activadoras de GTPasa , Ganglios Espinales/citología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/genética , Factores de Intercambio de Guanina Nucleótido/genética , Inmunoprecipitación/métodos , Indoles , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Microscopía Electrónica de Transmisión , Vaina de Mielina/ultraestructura , Neurregulina-1/farmacología , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Ratas , Ratas Sprague-Dawley , Células de Schwann/efectos de los fármacos , Células de Schwann/ultraestructura , Nervio Ciático/citología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Transfección , Proteína de Unión al GTP rac1/metabolismo , Proteínas de Unión al GTP rho/metabolismoRESUMEN
CD98hc is a type II transmembrane protein that covalently links to one of several L-type amino acid transporters. CD98hc was first identified as a lymphocyte activation marker. In this study, we examined the role that CD98hc plays in the functions of macrophages using tissue specific knock-out miceCD98hc (CD98hc(flox/-)LysM-cre mice). When isolated peritoneal macrophages were incubated for 48 h, the macrophages obtained from the knock-out mice showed round-shaped morphologies, while almost all of the cells obtained from the control mice were spindle-shaped. The macrophage functions such as the antigen-presenting, phagocytic, and fusion activities, have been reported to decrease in CD98hc-deficient peritoneal macrophages. In addition, when the CD98hc deficient macrophages were stimulated with either IFN-γ/LPS or IL-4, the production of NO(2) or arginase-I decreased in comparison to that observed in the control macrophages. These findings show that the CD98hc molecules play an important role in the activation and functions of macrophages.
Asunto(s)
Cadena Pesada de la Proteína-1 Reguladora de Fusión/inmunología , Macrófagos Peritoneales/inmunología , Animales , Células Cultivadas , Cadena Pesada de la Proteína-1 Reguladora de Fusión/genética , Ratones , Ratones Noqueados , FagocitosisRESUMEN
Cortisol induces attentional bias toward a negative stimulus and impaired attentional function. Depressed individuals have high levels of cortisol, and exhibit an attentional bias toward a depression-related stimulus and impaired processing speed and executive attention, which are components of attentional function. Therefore, the study tested the hypotheses that an acute increase in cortisol in response to a stressor is associated with attentional bias toward a depression-related stimulus and impaired processing speed and executive attention. Thirty-six participants were administered the dot-probe task for the measurement of attentional bias toward a depression-related stimulus and the Trail Making Test A and B for the measurement of processing speed and executive attention before and after a mental arithmetic task. It was revealed that attentional bias toward a depression-related stimulus following the stressor was observed only among the responders (i.e., participants with cortisol elevation in response to a stressor). On the other hand, no differences in the performance of processing speed and executive attention were noted between the responders and non-responders. The results indicate that acutely elevated cortisol is related to attentional bias, but is not related to processing speed and executive attention. The results have an implication for the etiology of depression.
Asunto(s)
Atención/fisiología , Depresión/fisiopatología , Función Ejecutiva/fisiología , Hidrocortisona/biosíntesis , Estrés Psicológico/fisiopatología , Adulto , Depresión/psicología , Femenino , Humanos , Hidrocortisona/metabolismo , Masculino , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Saliva/metabolismo , Estrés Psicológico/psicología , Adulto JovenRESUMEN
Studies have demonstrated that addiction leads to blunted responses of cortisol and sympathetic nervous system (SNS) to acute stressors; however, limited studies have examined the neuroendocrine and SNS stress responses in Internet addiction (IA). To examine acute stress responses in IA, the current study recruited a total of 76 Japanese university students and staff members (51 females and 25 males, mean age = 22.4 years, SD = 4.7), and measured the salivary cortisol, salivary alpha-amylase (sAA), and blood pressure (BP) responses to an acute stressor under stress or a nonstress placebo conditions in IA and non-IA groups. The results revealed that patients with IA showed a blunted cortisol response to a stressor. In contrast, no differences were found in the sAA and BP responses between the IA and non-IA groups. These results suggest that IA may be characterized by blunted cortisol responses in acute stress settings.
RESUMEN
We have already reported the nucleotide sequences of the NP, P/V, M, F and HN genes of human parainfluenza virus type 4A (hPIV-4A) and type 4B (hPIV-4B). Here, we have determined the sequences of the L protein genes as well as the gene start, intergenic and end sequences, thereby completing the full-length genome sequence of hPIV-4A and 4B. hPIV-4A and 4B have 17,052 and 17,304 nucleotides, respectively. The end sequence of hPIV-4, especially 4B, was extraordinarily long. In a comparison with members of the genus Rubulavirus, the hPIV-4 L proteins were closely related to those of mumps virus (MUV) and hPIV-2, less closely related to those of Menangle virus and Tioman virus, and more distantly related to those of Mapuera virus and porcine rubulavirus.
Asunto(s)
Codón de Terminación/genética , ADN Intergénico/genética , Virus de la Parainfluenza 4 Humana/clasificación , Virus de la Parainfluenza 4 Humana/genética , ARN Viral/genética , Sitio de Iniciación de la Transcripción , Animales , Secuencia de Bases , Células Cultivadas , Riñón/citología , Datos de Secuencia MolecularRESUMEN
BACKGROUND: Ne-Zake is the drinking of alcohol before sleeping for helping to fall asleep and sleep well, and Mukae-Zake is the drinking of alcohol in the morning for "calming down" or "curing hangovers". OBJECTIVE: We sought to examine the relationship of insomnia with Ne-Zake and Mukae-Zake among healthy middle-aged Japanese farmers. METHODS: In a cross-sectional study of 746 participants (mean age, 59.5 years; women, 25.9%), Ne-Zake and Mukae-Zake were defined based on a self-administered questionnaire. Insomnia was defined as the Athens Insomnia Scale Japanese version ≥6 or usage of sleeping pills in the previous year. Logistic regression was used to calculate odds ratio (OR) of insomnia related to Ne-Zake and Mukae-Zake adjusting for sex, age, presence of sleep-related disorders, frequency of alcohol consumption, and quantity of alcohol consumed per one occasion. RESULTS: We observed insomnia, Ne-Zake, and Mukae-Zake in 174 (23.3%), 140 (18.8%), and 37 (5.0%) participants, respectively. After adjustment for demographic and confounding factors, participants with Ne-Zake had a significantly higher prevalence of insomnia (OR 2.00 [95% confidence interval, 1.27-3.16]), compared to those without Ne-Zake. Mukae-Zake was also independently associated with a higher prevalence of insomnia among men (OR 3.26 [1.55-6.87]). Participants with both Ne-Zake and Mukae-Zake had a highly significant association with insomnia (OR 4.77 [2.01-11.3]) than those with neither Ne-Zake nor Mukae-Zake. Additionally, for insomnia, the association of Mukae-Zake was more pronounced than that of Ne-Zake (OR 4.09, 95% CI 1.14-14.7, p = 0.031; and OR 1.81, 95% CI 1.08-3.06, p = 0.026, respectively). CONCLUSION: Ne-Zake and Mukae-Zake were associated with insomnia independent of the quantity and frequency of alcohol consumption among Japanese farmers. This finding can be used for stratifying individuals with insomnia not only to improve sleep hygiene but also to prevent alcohol dependence by informing the general population that alcohol has a negative effect on sleep, contrary to popular beliefs.
Asunto(s)
Trastornos del Inicio y del Mantenimiento del Sueño , Consumo de Bebidas Alcohólicas/epidemiología , Estudios Transversales , Agricultores , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Sueño , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Problematic internet use (PIU) has been suggested in relation to psychological symptoms among schoolteachers, but the relationship with physical symptoms remains unclear. We examined whether PIU or longer Internet usage time is associated with neck pain in schoolteachers. METHODS: We conducted a cross-sectional study among 2582 teachers aged 20 years or older (35.6% women) in Shimane and Tottori, Japan in 2018. Neck pain was defined as ≥5 points on the Neck Disability Index. The Compulsive Internet Use Scale (CIUS) was used to assess PIU. Internet usage time on weekdays and weekends was divided into five groups: 0, 1-29, 30-59, 60-119, and ≥120 min/day. Logistic regression analysis was conducted to examine the association of the CIUS score and Internet usage time on weekdays or weekends with neck pain, adjusting for sex, age, position at school, insomnia, and psychological distress. RESULTS: We observed 800 (31.0%) teachers with neck pain. The median (interquartile range) of their CIUS scores was 7 (2, 14). A higher CIUS score was independently associated with a higher prevalence of neck pain (odds ratio of 4th vs. 1st quartiles, 1.41; 95% confidence interval, 1.06-1.87; trend P = .006). Compared with non-Internet users, Internet users on weekdays had almost double the odds of neck pain although the difference did not reach the customary level for designating statistical significance. CONCLUSIONS: In conclusion, teachers with higher scores in CIUS were associated with a higher prevalence of neck pain in Japan, suggesting adults with PIU being at risk of physical disorders.