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Given its central role in utilizing light energy, photoinduced electron transfer (PET) from an excited molecule has been widely studied1-6. However, even though microscopic photocurrent measurement methods7-11 have made it possible to correlate the efficiency of the process with local features, spatial resolution has been insufficient to resolve it at the molecular level. Recent work has, however, shown that single molecules can be efficiently excited and probed when combining a scanning tunnelling microscope (STM) with localized plasmon fields driven by a tunable laser12,13. Here we use that approach to directly visualize with atomic-scale resolution the photocurrent channels through the molecular orbitals of a single free-base phthalocyanine (FBPc) molecule, by detecting electrons from its first excited state tunnelling through the STM tip. We find that the direction and the spatial distribution of the photocurrent depend sensitively on the bias voltage, and detect counter-flowing photocurrent channels even at a voltage where the averaged photocurrent is near zero. Moreover, we see evidence of competition between PET and photoluminescence12, and find that we can control whether the excited molecule primarily relaxes through PET or photoluminescence by positioning the STM tip with three-dimensional, atomic precision. These observations suggest that specific photocurrent channels can be promoted or suppressed by tuning the coupling to excited-state molecular orbitals, and thus provide new perspectives for improving energy-conversion efficiencies by atomic-scale electronic and geometric engineering of molecular interfaces.
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The formation of excitons in organic molecules by charge injection is an essential process in organic light-emitting diodes (OLEDs)1-7. According to a simple model based on spin statistics, the injected charges form spin-singlet (S1) excitons and spin-triplet (T1) excitons in a 1:3 ratio2-4. After the first report of a highly efficient OLED2 based on phosphorescence, which is produced by the decay of T1 excitons, more effective use of these excitons has been the primary strategy for increasing the energy efficiency of OLEDs. Another route to improving OLED energy efficiency is reduction of the operating voltage2-6. Because T1 excitons have lower energy than S1 excitons (owing to the exchange interaction), use of the energy difference could-in principle-enable exclusive production of T1 excitons at low OLED operating voltages. However, a way to achieve such selective and direct formation of these excitons has not yet been established. Here we report a single-molecule investigation of electroluminescence using a scanning tunnelling microscope8-20 and demonstrate a simple method of selective formation of T1 excitons that utilizes a charged molecule. A 3,4,9,10-perylenetetracarboxylicdianhydride (PTCDA) molecule21-25 adsorbed on a three-monolayer NaCl film atop Ag(111) shows both phosphorescence and fluorescence signals at high applied voltage. In contrast, only phosphorescence occurs at low applied voltage, indicating selective formation of T1 excitons without creating their S1 counterparts. The bias voltage dependence of the phosphorescence, combined with differential conductance measurements, reveals that spin-selective electron removal from a negatively charged PTCDA molecule is the dominant formation mechanism of T1 excitons in this system, which can be explained by considering the exchange interaction in the charged molecule. Our findings show that the electron transport process accompanying exciton formation can be controlled by manipulating an electron spin inside a molecule. We anticipate that designing a device taking into account the exchange interaction could realize an OLED with a lower operating voltage.
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We present an alternative method to determine leaf CO2 assimilation rate (An ), eliminating the need for gas exchange measurements in proximal and remote sensing. This method combines the Farquhar-von Caemmerer-Berry photosynthesis model with mechanistic light reaction (MLR) theory and leaf energy balance (EB) analysis. The MLR theory estimates the actual electron transport rate (J) by leveraging chlorophyll fluorescence via pulse amplitude-modulated fluorometry for proximal sensing or sun-induced chlorophyll fluorescence measurements for remote sensing, along with spectral reflectance. The EB equation is used to directly estimate stomatal conductance from leaf temperature. In wheat and soybean, the MLR-EB model successfully estimated An variations, including midday depression, under various environmental and phenological conditions. Sensitivity analysis revealed that the leaf boundary layer conductance (gb ) played an equal, if not more, crucial role compared to the variables for J. This was primarily caused by the indirect influence of gb through the EB equation rather than its direct impact on convective CO2 exchange on the leaf. Although the MLR-EB model requires an accurate estimation of gb , it can potentially reduce uncertainties and enhance applicability in photosynthesis assessment when gas exchange measurements are unavailable.
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Dióxido de Carbono , Clorofila , Modelos Biológicos , Fotosíntesis , Hojas de la PlantaRESUMEN
Given its central role in photosynthesis and artificial energy-harvesting devices, energy transfer has been widely studied using optical spectroscopy to monitor excitation dynamics and probe the molecular-level control of energy transfer between coupled molecules. However, the spatial resolution of conventional optical spectroscopy is limited to a few hundred nanometres and thus cannot reveal the nanoscale spatial features associated with such processes. In contrast, scanning tunnelling luminescence spectroscopy has revealed the energy dynamics associated with phenomena ranging from single-molecule electroluminescence, absorption of localized plasmons and quantum interference effects to energy delocalization and intervalley electron scattering with submolecular spatial resolution in real space. Here we apply this technique to individual molecular dimers that comprise a magnesium phthalocyanine and a free-base phthalocyanine (MgPc and H2Pc) and find that locally exciting MgPc with the tunnelling current of the scanning tunnelling microscope generates a luminescence signal from a nearby H2Pc molecule as a result of resonance energy transfer from the former to the latter. A reciprocating resonance energy transfer is observed when exciting the second singlet state (S2) of H2Pc, which results in energy transfer to the first singlet state (S1) of MgPc and final funnelling to the S1 state of H2Pc. We also show that tautomerization of H2Pc changes the energy transfer characteristics within the dimer system, which essentially makes H2Pc a single-molecule energy transfer valve device that manifests itself by blinking resonance energy transfer behaviour.
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BACKGROUND AND AIMS: Most perennial plants memorize cold stress for a certain period and retrieve the memories for cold acclimation and deacclimation, which leads to seasonal changes in cold-hardiness. Therefore, a model for evaluating cold stress memories is required for predicting cold-hardiness and for future frost risk assessments under warming climates. In this study we develop a new dynamic model of cold-hardiness by introducing a function imitating past temperature memory in the processes of cold acclimation and deacclimation. METHODS: We formulated the past temperature memory for plants using thermal time weighted by a forgetting function, and thereby proposed a dynamic model of cold-hardiness. We used the buds of tea plants (Camellia sinensis) from two cultivars, 'Yabukita' and 'Yutakamidori', to calibrate and validate this model based on 10 years of observed cold-hardiness data. KEY RESULTS: The model captured more than 90 % of the observed variation in cold-hardiness and predicted accurate values for both cultivars, with root mean square errors of ~1.0 °C. The optimized forgetting function indicated that the tea buds memorized both short-term (recent days) and long-term (previous months) temperatures. The memories can drive short-term processes such as increasing/decreasing the content of carbohydrates, proteins and antioxidants in the buds, as well as long-term processes such as determining the bud phenological stage, both of which vary with cold-hardiness. CONCLUSIONS: The use of a forgetting function is an effective means of understanding temperature memories in plants and will aid in developing reliable predictions of cold-hardiness for various plant species under global climate warming.
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Frío , Respuesta al Choque por Frío , Aclimatación , Estaciones del Año , Té , TemperaturaRESUMEN
Electron transport and optical properties of a single molecule in contact with conductive materials have attracted considerable attention because of their scientific importance and potential applications. With the recent progress in experimental techniques, especially by virtue of scanning tunneling microscope (STM)-induced light emission, where the tunneling current of the STM is used as an atomic-scale source for induction of light emission from a single molecule, it has become possible to investigate single-molecule properties at subnanometer spatial resolution. Despite extensive experimental studies, the microscopic mechanism of electronic excitation of a single molecule in STM-induced light emission has yet to be clarified. Here we present a formulation of single-molecule electroluminescence driven by electron transfer between a molecule and metal electrodes based on a many-body state representation of the molecule. The effects of intramolecular Coulomb interaction on conductance and luminescence spectra are investigated using the nonequilibrium Hubbard Green's function technique combined with first-principles calculations. We compare simulation results with experimental data and find that the intramolecular Coulomb interaction is crucial for reproducing recent experiments for a single phthalocyanine molecule. The developed theory provides a unified description of the electron transport and optical properties of a single molecule in contact with metal electrodes driven out of equilibrium, and thereby, it contributes to a microscopic understanding of optoelectronic conversion in single molecules on solid surfaces and in nanometer-scale junctions.
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We report a patient with hypertrophic pachymeningitis and symptomatic stenosis of the superior sagittal sinus. A 71-year-old man presented with right hemiparesis, sensory-dominant aphasia, and right hemispatial neglect that had been worsening over 2 weeks. Computed tomography showed isodense crescent-shaped lesions deforming the surface of the left cerebral hemisphere, mimicking a subdural hematoma with atypical perifocal edema in the left parietal lobe. Magnetic resonance imaging showed diffuse thickening of the dura mater with contrast enhancement of his left cerebral hemisphere. Histopathological examination of the dural specimen obtained by burr-hole surgery revealed mononuclear inflammatory cell infiltration, and he was diagnosed with hypertrophic pachymeningitis. Dynamic cerebral angiography showed superior sagittal sinus stenosis with reduced venous flow through the left parietal lobe. Administration of high-dose steroid therapy led to neurological improvement. In the case of a subdural mass with atypical parenchymal edema such as a chronic subdural hematoma, other etiology should be taken into consideration.
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Hiperemia/cirugía , Meningitis/cirugía , Anciano , Humanos , Hiperemia/complicaciones , Hiperemia/diagnóstico por imagen , Hipertrofia/diagnóstico por imagen , Hipertrofia/etiología , Hipertrofia/cirugía , Imagen por Resonancia Magnética , Masculino , Meningitis/diagnóstico por imagen , Meningitis/etiología , Imagen Multimodal , Nariz , Tomografía Computarizada por Rayos XRESUMEN
We investigate the near-field interaction between an isolated free-base phthalocyanine molecule and a plasmon localized in the gap between an NaCl-covered Ag(111) surface and the tip apex of a scanning tunneling microscope. When the tip is located in the close proximity of the molecule, asymmetric dips emerge in the broad luminescence spectrum of the plasmon generated by the tunneling current. The origin of the dips is explained by energy transfer between the plasmon and molecular excitons and a quantum mechanical interference effect, where molecular vibrations provide additional degrees of freedom in the dynamic process.
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The heart is electrically and mechanically controlled as a syncytium by the autonomic nervous system. The cardiac nervous system comprises the sympathetic, parasympathetic, and sensory nervous systems that together regulate heart function on demand. Sympathetic electric activation was initially considered the main regulator of cardiac function; however, modern molecular biotechnological approaches have provided a new dimension to our understanding of the mechanisms controlling the cardiac nervous system. The heart is extensively innervated, although the innervation density is not uniform within the heart, being high in the subepicardium and the special conduction system. We and others showed previously that the balance between neural chemoattractants and chemorepellents determine cardiac nervous development, with both factors expressed in heart. Nerve growth factor is a potent chemoattractant synthesized by cardiomyocytes, whereas Sema3a is a neural chemorepellent expressed specifically in the subendocardium. Disruption of this well-organized molecular balance and innervation density can induce sudden cardiac death due to lethal arrhythmias. In diseased hearts, various causes and mechanisms underlie cardiac sympathetic abnormalities, although their detailed pathology and significance remain contentious. We reported that cardiac sympathetic rejuvenation occurs in cardiac hypertrophy and, moreover, interleukin-6 cytokines secreted from the failing myocardium induce cholinergic transdifferentiation of the cardiac sympathetic system via a gp130 signaling pathway, affecting cardiac performance and prognosis. In this review, we summarize the molecular mechanisms involved in sympathetic development, maturation, and transdifferentiation, and propose their investigation as new therapeutic targets for heart disease.
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Transdiferenciación Celular , Cardiopatías/metabolismo , Corazón/inervación , Factores de Crecimiento Nervioso/metabolismo , Neurogénesis , Sistema Nervioso Simpático/metabolismo , Animales , Cardiopatías/fisiopatología , Cardiopatías/terapia , Humanos , Regeneración Nerviosa , Transducción de Señal , Sistema Nervioso Simpático/embriología , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
Sympathetic innervation is critical for effective cardiac function. However, the developmental and regulatory mechanisms determining the density and patterning of cardiac sympathetic innervation remain unclear, as does the role of this innervation in arrhythmogenesis. Here we show that a neural chemorepellent, Sema3a, establishes cardiac sympathetic innervation patterning. Sema3a is abundantly expressed in the trabecular layer in early-stage embryos but is restricted to Purkinje fibers after birth, forming an epicardial-to-endocardial transmural sympathetic innervation patterning. Sema3a(-/-) mice lacked a cardiac sympathetic innervation gradient and exhibited stellate ganglia malformation, which led to marked sinus bradycardia due to sympathetic dysfunction. Cardiac-specific overexpression of Sema3a in transgenic mice (SemaTG) was associated with reduced sympathetic innervation and attenuation of the epicardial-to-endocardial innervation gradient. SemaTG mice demonstrated sudden death and susceptibility to ventricular tachycardia, due to catecholamine supersensitivity and prolongation of the action potential duration. We conclude that appropriate cardiac Sema3a expression is needed for sympathetic innervation patterning and is critical for heart rate control.
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Sistema de Conducción Cardíaco/fisiología , Corazón/fisiología , Semaforina-3A/fisiología , Acetilcolinesterasa/metabolismo , Envejecimiento , Animales , Regulación de la Expresión Génica , Corazón/crecimiento & desarrollo , Ratones , Ratones Noqueados , Ratones Transgénicos , Semaforina-3A/deficiencia , Semaforina-3A/genética , Sistema Nervioso Simpático/fisiología , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
The nucleus accumbens (NAc) serves as a key neural substrate that controls acute and adaptive behavioral responses to cocaine administration. In this circuit, inputs from the NAc are transmitted through two parallel pathways, named the direct and indirect pathways, and converge at the substantia nigra pars reticulata (SNr). Our previous study using reversible neurotransmission blocking (RNB) of each pathway revealed that the dual stimulation of the SNr by both pathways is necessary for the acute response, but that the direct pathway predominantly controls the adaptive response to repeated cocaine administration. This study aimed at exploring the pathway-specific mechanism of cocaine actions at the convergent SNr. We examined a genome-wide expression profile of the SNr of three types of experimental mice: the direct pathway-blocked D-RNB mice, the indirect pathway-blocked I-RNB mice, and wild-type mice. We identified the up-regulation of ephrinA5, EphA4, and EphA5 specific to D-RNB mice during both acute and adaptive responses to cocaine administration. The activation by EphA4 and EphA5 in the SNr of wild-type mice by use of the immunoadhesin technique suppressed the adaptive response to repeated cocaine administration. Furthermore, cocaine exposure stimulated the phosphorylation of Erk1/2 in ephrinA5-expressing SNr cells in a direct pathway-dependent manner. The results have demonstrated that the ephrinA5-EphA4/EphA5 system plays an important role in the direct pathway-dependent regulation of the SNr in both acute and adaptive cocaine responses and would provide valuable therapeutic targets of cocaine addiction.
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Cocaína/farmacología , Efrina-A5/genética , Receptor EphA4/genética , Receptor EphA5/genética , Sustancia Negra/efectos de los fármacos , Anestésicos Locales/administración & dosificación , Anestésicos Locales/farmacología , Animales , Cocaína/administración & dosificación , Efrina-A5/metabolismo , Perfilación de la Expresión Génica , Inmunohistoquímica , Ratones , Ratones Transgénicos , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Actividad Motora/efectos de los fármacos , Vías Nerviosas/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosforilación/efectos de los fármacos , Receptor EphA4/metabolismo , Receptor EphA5/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sustancia Negra/metabolismo , Toxina Tetánica/genética , Toxina Tetánica/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Cypher long (CypherL) and short (CypherS) isoforms are distinguished from each other by the presence and absence of three C-terminal LIM domains, respectively. Cypher isoforms are developmentally regulated, and mutations affecting both long and short isoforms are linked to muscle disease in humans. Given these data, we hypothesized that various Cypher isoforms play overlapping and unique roles in striated muscle. To determine the specific role of Cypher isoforms in striated muscle, we generated two mouse lines in which either CypherS or CypherL isoforms were specifically deleted. Mice specifically, deficient in CypherS isoforms had no detectable muscle phenotype. In contrast, selective loss of CypherL isoforms resulted in partial neonatal lethality. Surviving mutants exhibited growth retardation and late-onset dilated cardiomyopathy, which was associated with cardiac fibrosis and calcification, leading to premature adult mortality. At a young age, preceding development of cardiomyopathy, hearts from these mutants exhibited defects in both Z-line ultrastructure and specific aberrations in calcineurin-NFAT and protein kinase C pathways. Earlier onset of cardiac dilation relative to control wild-type mice was observed in young CypherL isoform knockout mice consequent to pressure overload, suggesting a greater susceptibility to the disease. In summary, we have identified unique roles for CypherL isoforms in maintaining Z-line ultrastructure and signaling that are distinct from the roles of CypherS isoforms, while highlighting the contribution of mutations in the long isoforms to the development of dilated cardiomyopathy.
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Cardiomiopatía Dilatada/genética , Proteínas Portadoras/genética , Eliminación de Gen , Proteínas de Homeodominio/genética , Proteínas Adaptadoras Transductoras de Señales , Animales , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/patología , Proteínas Portadoras/metabolismo , Modelos Animales de Enfermedad , Femenino , Proteínas de Homeodominio/metabolismo , Humanos , Proteínas con Dominio LIM , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Músculo Estriado/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismoRESUMEN
The avascularity of cardiac valves is abrogated in several valvular heart diseases (VHDs). This study investigated the molecular mechanisms underlying valvular avascularity and its correlation with VHD. Chondromodulin-I, an antiangiogenic factor isolated from cartilage, is abundantly expressed in cardiac valves. Gene targeting of chondromodulin-I resulted in enhanced Vegf-A expression, angiogenesis, lipid deposition and calcification in the cardiac valves of aged mice. Echocardiography showed aortic valve thickening, calcification and turbulent flow, indicative of early changes in aortic stenosis. Conditioned medium obtained from cultured valvular interstitial cells strongly inhibited tube formation and mobilization of endothelial cells and induced their apoptosis; these effects were partially inhibited by chondromodulin-I small interfering RNA. In human VHD, including cases associated with infective endocarditis, rheumatic heart disease and atherosclerosis, VEGF-A expression, neovascularization and calcification were observed in areas of chondromodulin-I downregulation. These findings provide evidence that chondromodulin-I has a pivotal role in maintaining valvular normal function by preventing angiogenesis that may lead to VHD.
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Aorta/patología , Enfermedades de las Válvulas Cardíacas/patología , Péptidos y Proteínas de Señalización Intercelular/fisiología , Proteínas de la Membrana/fisiología , Válvula Mitral/patología , Neovascularización Patológica , Anciano , Inhibidores de la Angiogénesis/farmacología , Animales , Aorta/metabolismo , Medios de Cultivo Condicionados/metabolismo , Ecocardiografía , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos ICR , Ratones Transgénicos , Persona de Mediana Edad , Válvula Mitral/metabolismo , Ratas , Ratas WistarRESUMEN
CO2 enrichment is an essential environmental control technology due to its significantly enhancing effect on crop production capacity. Despite being a key energy consumer in protected agriculture (i.e. greenhouse systems), CO2 enrichment remains at a low energy use efficiency level, highlighting the need for developing more energy-efficiency strategies for CO2 enrichment. Therefore, this study employed the computational fluid dynamics (CFD) simulation method to replicate the CO2 diffusion process resulting from CO2 enrichment in three commercial strawberry greenhouses with varying geometric characteristics. Based on the CFD-simulated CO2 concentration distributions, the leaf photosynthetic rate was calculated using a mathematical model group. The CO2 enrichment efficiency was then analysed by calculating the ratio of increased photosynthesis across the cultivation area to the amount of energy (in CO2 equivalent) used. The efficiency peaked when the average CO2 concentration was approximately 500 µmol mol-1, thereby providing guidance for determining the target concentration of CO2 enrichment in production. Although this study is limited as the CFD simulation only considered a typical short-period CO2 enrichment event, future research will provide a broader analysis by considering changes throughout the day.
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Dióxido de Carbono , Fotosíntesis , Hojas de la Planta , Agricultura , Producción de CultivosRESUMEN
The efficient induction of cardiomyocyte differentiation from embryonic stem (ES) cells is crucial for cardiac regenerative medicine. Although Wnts play important roles in cardiac development, complex questions remain as to when, how and what types of Wnts are involved in cardiogenesis. We found that Wnt2 was strongly up-regulated during cardiomyocyte differentiation from ES cells. Therefore, we investigated when and how Wnt2 acts in cardiogenesis during ES cell differentiation. Wnt2 was strongly expressed in the early developing murine heart. We applied this embryonic Wnt2 expression pattern to ES cell differentiation, to elucidate Wnt2 function in cardiomyocyte differentiation. Wnt2 knockdown revealed that intrinsic Wnt2 was essential for efficient cardiomyocyte differentiation from ES cells. Moreover, exogenous Wnt2 increased cardiomyocyte differentiation from ES cells. Interestingly, the effects on cardiogenesis of intrinsic Wnt2 knockdown and exogenous Wnt2 addition were temporally restricted. During cardiomyocyte differentiation from ES cells, Wnt2 didn't activate canonical Wnt pathway but utilizes JNK/AP-1 pathway which is required for cardiomyocyte differentiation from ES cells. Therefore we conclude that Wnt2 plays strong positive stage-specific role in cardiogenesis through non-canonical Wnt pathway in murine ES cells.
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Diferenciación Celular , Células Madre Embrionarias/citología , Mesodermo/citología , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Transducción de Señal , Proteína wnt2/metabolismo , Animales , Diferenciación Celular/genética , Línea Celular , Células Cultivadas , Chlorocebus aethiops , Células Madre Embrionarias/metabolismo , Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Silenciador del Gen , Corazón/embriología , Humanos , Sistema de Señalización de MAP Quinasas , Mesodermo/metabolismo , Ratones , Ratones Endogámicos ICR , Ratones Transgénicos , Factores de Tiempo , Factor de Transcripción AP-1/metabolismo , Proteína wnt2/genéticaRESUMEN
RATIONALE: The Z-line, alternatively termed the Z-band or Z-disc, is a highly ordered structure at the border between 2 sarcomeres. Enigma subfamily proteins (Enigma, Enigma homolog protein, and Cypher) of the PDZ-LIM domain protein family are Z-line proteins. Among the Enigma subfamily, Cypher has been demonstrated to play a pivotal role in the structure and function of striated muscle, whereas the role of Enigma homolog protein (ENH) in muscle remains largely unknown. OBJECTIVE: We studied the role of Enigma homolog protein in the heart using global and cardiac-specific ENH knockout mouse models. METHODS AND RESULTS: We identified new exons and splice isoforms for ENH in the mouse heart. Impaired cardiac contraction and dilated cardiomyopathy were observed in ENH null mice. Mice with cardiac specific ENH deletion developed a similar dilated cardiomyopathy. Like Cypher, ENH interacted with Calsarcin-1, another Z-line protein. Moreover, biochemical studies showed that ENH, Cypher short isoform and Calsarcin-1 are within the same protein complex at the Z-line. Cypher short isoform and Calsarcin-1 proteins are specifically downregulated in ENH null hearts. CONCLUSIONS: We have identified an ENH-CypherS-Calsarcin protein complex at the Z-line. Ablation of ENH leads to destabilization of this protein complex and dilated cardiomyopathy.
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Proteínas Adaptadoras Transductoras de Señales/deficiencia , Cardiomiopatía Dilatada/genética , Proteínas de Microfilamentos/deficiencia , Proteínas Adaptadoras Transductoras de Señales/genética , Empalme Alternativo , Animales , Cardiomiopatía Dilatada/fisiopatología , Proteínas Portadoras/genética , Proteínas Portadoras/fisiología , Exones , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/fisiología , Proteínas con Dominio LIM , Ratones , Ratones Noqueados , Proteínas de Microfilamentos/genética , Proteínas Musculares/genética , Contracción Miocárdica/genética , Plásmidos , Reacción en Cadena de la Polimerasa , Isoformas de Proteínas/genética , Sístole/genéticaRESUMEN
OBJECTIVE: We recently demonstrated that primitive neural crest-derived (NC) cells migrate from the cardiac neural crest during embryonic development and remain in the heart as dormant stem cells, with the capacity to differentiate into various cell types, including cardiomyocytes. Here, we examined the migration and differentiation potential of these cells on myocardial infarction (MI). METHODS AND RESULTS: We obtained double-transgenic mice by crossing protein-0 promoter-Cre mice with Floxed-enhanced green fluorescent protein mice, in which the NC cells express enhanced green fluorescent protein. In the neonatal heart, NC stem cells (NCSCs) were localized predominantly in the outflow tract, but they were also distributed in a gradient from base to apex throughout the ventricular myocardium. Time-lapse video analysis revealed that the NCSCs were migratory. Some NCSCs persisted in the adult heart. On MI, NCSCs accumulated at the ischemic border zone area (BZA), which expresses monocyte chemoattractant protein-1 (MCP-1). Ex vivo cell migration assays demonstrated that MCP-1 induced NCSC migration and that this chemotactic effect was significantly depressed by an anti-MCP-1 antibody. Small NC cardiomyocytes first appeared in the BZA 2 weeks post-MI and gradually increased in number thereafter. CONCLUSIONS: These results suggested that NCSCs migrate into the BZA via MCP-1/CCR2 signaling and contribute to the provision of cardiomyocytes for cardiac regeneration after MI.
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Diferenciación Celular , Linaje de la Célula , Movimiento Celular , Infarto del Miocardio/patología , Miocitos Cardíacos/patología , Cresta Neural/embriología , Células Madre/patología , Animales , Proliferación Celular , Células Cultivadas , Quimiocina CCL2/metabolismo , Modelos Animales de Enfermedad , Proteínas Fluorescentes Verdes/genética , Integrasas/genética , Ratones , Ratones Transgénicos , Proteína P0 de la Mielina/genética , Infarto del Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Activadores Plasminogénicos/genética , Regiones Promotoras Genéticas , Interferencia de ARN , Receptores CCR2/genética , Receptores CCR2/metabolismo , Regeneración , Transducción de Señal , Células Madre/metabolismo , Factores de Tiempo , Grabación en Video , Proteína Wnt1/genéticaRESUMEN
Although the association between cardiac dysfunction and subarachnoid hemorrhage (SAH) has been recognized, its precise underlying mechanism remains unknown. Furthermore, no suitable animal models are available to study this association. Here, we established an appropriate animal model of SAH-induced cardiac dysfunction and elucidated its mechanism. In this rat model, contrast-enhanced computed tomography of the brain confirmed successful induction of SAH. Electrocardiography detected abnormalities in 55% of the experimental animals, while echocardiography indicated cardiac dysfunction in 30% of them. Further evaluation of left ventriculography confirmed cardiac dysfunction, which was transient and recovered over time. Additionally, in this SAH model, the expression of the acute phase reaction protein, proto-oncogene c-Fos increased in the paraventricular hypothalamic nucleus (PVN), the sympathetic nerve center of the brain. Polymerase chain reaction analysis revealed that the SAH model with cardiac dysfunction had higher levels of the macrophage-associated chemokine (C-X-C motif) ligand 1 (CXCL-1) and chemokine (C-C motif) ligand 2 (CCL-2) than the SAH model without cardiac dysfunction. Our results suggested that SAH caused inflammation and macrophage activation in the PVN, leading to sympathetic hyperexcitability that might cause cardiac dysfunction directly and indirectly. This animal model may represent a powerful tool to investigate the mechanisms of the brain-heart pathway.
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Substantial emotional or physical stress may lead to an imbalance in the brain, resulting in stress cardiomyopathy (SC) and transient left ventricular (LV) apical ballooning. Even though these conditions are severe, their precise underlying mechanisms remain unclear. Appropriate animal models are needed to elucidate the precise mechanisms. In this study, we established a new animal model of epilepsy-induced SC. The SC model showed an increased expression of the acute phase reaction protein, c-Fos, in the paraventricular hypothalamic nucleus (PVN), which is the sympathetic nerve center of the brain. Furthermore, we observed a significant upregulation of neuropeptide Y (NPY) expression in the left stellate ganglion (SG) and cardiac sympathetic nerves. NPY showed neither positive nor negative inotropic and chronotropic effects. On the contrary, NPY could interrupt ß-adrenergic signaling in cardiomyocytes when exposure to NPY precedes exposure to noradrenaline. Moreover, its elimination in the left SG via siRNA treatment tended to reduce the incidence of SC. Thus, our results indicated that upstream sympathetic activation induced significant upregulation of NPY in the left SG and cardiac sympathetic nerves, resulting in cardiac dysfunctions like SC.
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Ways to characterize and control excited states at the single-molecule and atomic levels are needed to exploit excitation-triggered energy-conversion processes. Here, we present a single-molecule spectroscopic method with micro-electron volt energy and submolecular-spatial resolution using laser driving of nanocavity plasmons to induce molecular luminescence in scanning tunneling microscopy. This tunable and monochromatic nanoprobe allows state-selective characterization of the energy levels and linewidths of individual electronic and vibrational quantum states of a single molecule. Moreover, we demonstrate that the energy levels of the states can be finely tuned by using the Stark effect and plasmon-exciton coupling in the tunneling junction. Our technique and findings open a route to the creation of designed energy-converting functions by using tuned energy levels of molecular systems.