RESUMEN
The bHLH transcription factors SHARP1 and SHARP2 are partially redundant modulators of the circadian system. SHARP1/DEC2 has been shown to control sleep length in humans and sleep architecture is also altered in double mutant mice (S1/2(-/-)). Because of the importance of sleep for memory consolidation, we investigated the role of SHARP1 and SHARP2 in cognitive processing. S1/2(-/-) mice show enhanced cortex (Cx)-dependent remote fear memory formation as well as improved reversal learning, but do not display alterations in hippocampus (Hi)-dependent recent fear memory formation. SHARP1 and SHARP2 single null mutants do not display any cognitive phenotype supporting functional redundancy of both factors. Molecular and biochemical analyses revealed elevated insulin-related growth factor 2 (IGF2) signaling and increased phosphorylation of MAPK and S6 in the Cx but not the Hi of S1/2(-/-) mice. No changes were detected in single mutants. Moreover, adeno-associated virus type 2-mediated IGF2 overexpression in the anterior cingulate cortex enhanced remote fear memory formation and the analysis of forebrain-specific double null mutants of the Insulin and IGF1 receptors revealed their essential function for memory formation. Impaired fear memory formation in aged S1/2(-/-) mice indicates that elevated IGF2 signaling in the long term, however, has a negative impact on cognitive processing. In summary, we conclude that the bHLH transcription factors SHARP1 and SHARP2 are involved in cognitive processing by controlling Igf2 expression and associated signaling cascades. Our analyses provide evidence that the control of sleep and memory consolidation may share common molecular mechanisms.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Corteza Cerebral/metabolismo , Proteínas de Homeodominio/metabolismo , Factor II del Crecimiento Similar a la Insulina/metabolismo , Memoria a Largo Plazo , Transducción de Señal , Factores de Transcripción/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Western Blotting , Expresión Génica , Proteínas de Homeodominio/genética , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fosforilación , Interferencia de ARN , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Factores de Transcripción/genéticaRESUMEN
In this research, the feasibility study of revamping of simulated moving bed for paraxylene separation in ELUXYL process to produce meta-xylene using industrial Ba-faujasite exchanged adsorbent by changing operating condition (temperature and pressure) were examined experimentally and theoretically. Two different mixed-xylene feed cases (with and without presence of para-xylene) were considered. Different sets of temperature and pressure were evaluated with the help of equilibrium and dynamic experiments to obtain optimum operating condition in a favor of separation of meta-xylene. Results confirm that in the presence of para-xylene in a feed, selectivity of the adsorbent could not change towards meta-xylene. But, in the absence of para in some pressure and temperature meta-xylene was more selective than ortho and ethylbenzene. Finally, by the means of statistical experimental design method the results of all experiments were compered and an optimum temperature and pressure were found. Breakthrough experiment in optimum condition showed MX/OX and MX/EB selectivity as 1.83 and 1.15, respectively. Furthermore, the design and simulation of the real industrial SMB plant was performed in Aspen Chromatography and HYSYS software to evaluate the real performance of MX separation. Simulation results showed the final purification in SMB plant can be reached to 83.91%. At the end, for the aim of promoting purity by considering extra distillation towers the purity of meta-xylene was achieved by 96%. The economical investigation showed that by considering 700$/ton for feed supplied, the process can be satisfactory from economical point of view.
RESUMEN
Ulmus carpinifolia and Fraxinus excelsior tree leaves, which are in great supply in Iran, were evaluated for removal of Pb(II), Cd(II) and Cu(II) from aqueous solution. Maximum biosorption capacities for U. carpinifolia and F. excelsior were measured as 201.1, 172.0 mg/g for Pb(II), 80.0, 67.2 mg/g for Cd(II) and 69.5, 33.1 mg/g for Cu(II), respectively. For both sorbents the most effective pH range was found to be 2-5 for Pb(II), 3-5 for Cd(II) and 4-5 for Cu(II). Metal ion biosorption increased as the ratio of metal solution to the biomass quantity decreased. Conversely, biosorption/g biosorbent decreased as the quantity of biomass increased. The biosorption of metal ions increased as the initial metal concentration increased. Biosorption capacities of metal ions were in the following order: Pb(II)>Cd(II)>Cu(II). The equilibrium data for Pb(II) and Cu(II) best fit the Langmuir adsorption isotherm model. Kinetic studies showed that the biosorption rates could be described by a second-order expression. Both the sorbents could be regenerated using 0.2 M HCl during repeated biosorption-desorption cycles with no loss in the efficiency of the Cu(II) removal observed. Biosorption of Pb(II), Cd(II) and Cu(II) was investigated in the presence of Na, K, Mg and Ca ions. The results from these studies show a novel way of using U. carpinifolia and F. excelsior tree leaves to remove Pb(II), Cd(II) and Cu(II) from metal-polluted waters.
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Fraxinus/química , Metales Pesados/aislamiento & purificación , Hojas de la Planta/química , Ulmus/química , Adsorción , Biomasa , Concentración de Iones de Hidrógeno , Cinética , Soluciones , Espectroscopía Infrarroja por Transformada de Fourier , AguaRESUMEN
Sulforhodamine 101 (SR101) is widely used for astrocyte identification, though the labeling mechanism remains unknown and the efficacy of labeling in different brain regions is heterogeneous. By combining region-specific isolation of astrocytes followed by transcriptome analysis, two-photon excitation microscopy, and mouse genetics, we identified the thyroid hormone transporter OATP1C1 as the SR101-uptake transporter in hippocampus and cortex.
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Astrocitos/metabolismo , Colorantes , Hipocampo/citología , Proteínas de Transporte de Catión Orgánico/metabolismo , Rodaminas , Animales , Animales Recién Nacidos , Corteza Cerebral/citología , Biología Computacional , Electrólitos/líquido cefalorraquídeo , Femenino , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Técnicas In Vitro , Masculino , Ratones , Ratones Transgénicos , Optogenética , Proteínas de Transporte de Catión Orgánico/genéticaRESUMEN
Increasing evidence suggests that clock genes may be implicated in a spectrum of psychiatric diseases, including sleep and mood related disorders as well as schizophrenia. The bHLH transcription factors SHARP1/DEC2/BHLHE41 and SHARP2/DEC1/BHLHE40 are modulators of the circadian system and SHARP1/DEC2/BHLHE40 has been shown to regulate homeostatic sleep drive in humans. In this study, we characterized Sharp1 and Sharp2 double mutant mice (S1/2-/-) using online EEG recordings in living animals, behavioral assays and global gene expression profiling. EEG recordings revealed attenuated sleep/wake amplitudes and alterations of theta oscillations. Increased sleep in the dark phase is paralleled by reduced voluntary activity and cortical gene expression signatures reveal associations with psychiatric diseases. S1/2-/- mice display alterations in novelty induced activity, anxiety and curiosity. Moreover, mutant mice exhibit impaired working memory and deficits in prepulse inhibition resembling symptoms of psychiatric diseases. Network modeling indicates a connection between neural plasticity and clock genes, particularly for SHARP1 and PER1. Our findings support the hypothesis that abnormal sleep and certain (endo)phenotypes of psychiatric diseases may be caused by common mechanisms involving components of the molecular clock including SHARP1 and SHARP2.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/deficiencia , Ritmo Circadiano/fisiología , Endofenotipos/metabolismo , Trastornos Mentales/fisiopatología , Proteínas Represoras/deficiencia , Sueño/fisiología , Factores de Transcripción/deficiencia , Animales , Ansiedad/complicaciones , Ansiedad/fisiopatología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Ritmo Circadiano/efectos de los fármacos , Clozapina/farmacología , Clozapina/uso terapéutico , Conducta Exploratoria/efectos de los fármacos , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Redes Reguladoras de Genes , Masculino , Trastornos Mentales/complicaciones , Ratones Endogámicos C57BL , Inhibición Prepulso/efectos de los fármacos , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Sueño/efectos de los fármacos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Vigilia/efectos de los fármacos , Vigilia/genéticaRESUMEN
In mammals, 24-h rhythms are controlled by a hierarchical system of endogenous clocks, with a circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus that synchronizes peripheral oscillators throughout the body. The molecular clock machinery is regulated by interlocked transcriptional translational feedback loops (TTLs). The core TTL includes the transcriptional modulators PER (1-3) and CRY (1/2) that feed back on their own expression by interaction with CLOCK/BMAL1. An accessory loop involving the transcription factors DEC1 and DEC2 has been described that also impinges on CLOCK/BMAL1-mediated transactivation. In Drosophila, the DEC ortholog CWO shows synergistic activity to PER. This prompted the authors to analyze PER1-DEC interaction in the mammalian SCN. They generated Per1/Dec double and triple mutant mice to monitor activity rhythms under entrained and free-running conditions. Furthermore, they analyzed expression of the clock genes Per2, Rev-Erbα, and Bmal1 in wild-type and Per1/Dec mutant SCN by in situ hybridization. The experiments reveal a critical role for Per1-Dec interaction in regulating activity phase under entrained conditions. In constant darkness, a synergistic function for Per1 and Dec1/2 in period regulation was found, correlating with disrupted clock gene mRNA levels in the SCN. Luciferase reporter gene assays indicate an activatory function of DECs on Bmal1 expression. Together, the results suggest a partially redundant and bidirectional regulatory function for the 2 Dec genes in the TTL and a conservation of Per-Dec (Cwo) synergism between vertebrate and invertebrate clocks.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Relojes Biológicos/fisiología , Ritmo Circadiano/fisiología , Proteínas de Drosophila/genética , Proteínas de Homeodominio/genética , Actividad Motora/fisiología , Proteínas Circadianas Period/genética , Factores de Transcripción/genética , Factores de Transcripción ARNTL/genética , Factores de Transcripción ARNTL/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Proteínas de Drosophila/metabolismo , Genes Reporteros , Proteínas de Homeodominio/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Circadianas Period/metabolismo , Núcleo Supraquiasmático/citología , Núcleo Supraquiasmático/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Platanus tree leaves were successfully used as a novel sorbent for removing of methylene blue (MB) dye from aqueous solutions. A 2(3) full factorial design was performed for screening of the main factors. The pH, initial concentration of dye (C(d)) and amount of sorbent (m) were considered to be the three main factors at two different levels. It was found that all these factors and their interactions were significant at a certain confidence level (p < 0.05). Doehlert response surface design was applied (13 runs) for a further inspection of the main factors effect, which led to an empirical model. An analysis of the variances (ANOVA) and relevant tests, such as lack-of-fit and residual probability plot, confirmed the validity of the suggested model. A desirability function was used for the simultaneous optimization of both the removal efficiency (R%) and the maximum capacity of the sorbent (q). Plots of the response surface, through visualization of the suggested model, clearly showed the interactions between the main variables and their effects on the response.
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Azul de Metileno/metabolismo , Árboles/metabolismo , Absorción , Algoritmos , Análisis de Varianza , Concentración de Iones de Hidrógeno , Cinética , Azul de Metileno/química , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Estándares de Referencia , Análisis de Regresión , Programas Informáticos , Árboles/químicaRESUMEN
The present study introduces Robinia tree leaves as a novel and efficient biosorbent for removing Pb(II) from aqueous solutions. In order to reduce the large number of experiments and find the highest removal efficiency of Pb(II), a set of full 2(3) factorial design with two blocks were performed in duplicate (16 experiments). In all experiments, the contact time was fixed at 25 min. The main interaction effects of the three factors including sorbent mass, pH and initial concentration of metal-ion were considered. By using Student's t-test and analysis of variances (ANOVA), the main factors, which had the highest effect on the removal process, were identified. Twenty-six experiments were designed according to Doehlert response surface design to obtain a mathematical model describing functional relationship between response and main independent variables. The most suitable regression model, that fitted the experimental data extremely well, was chosen according to the lack-of-fit-test and adjusted R(2) value. Finally, after checking for possible outliers, the optimum conditions for maximum removal of Pb(II) from aqueous solution were obtained. The best conditions were calculated to be as: initial concentration of Pb(II)=40 mg L(-1), pH 4.6 and concentration of sorbet equal to 27.3 g L(-1).