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Expanding loco-regional nodes harvesting is expected to increase survival. This improvement may be associated to stage migration (SM). However, the great bulk of harvested lymph nodes observed in large dissections is negative. M&M: 830 patients who received R0 gastrectomy for adenocarcinoma were included. pN+ patients with <26 nodes (n = 209) were included for a simulation to "offer 26 nodes" - SM (proportional and exponential based) was simulated and analysed through machine learning algorithms. Overall Survival (OS), in native and simulated stages, were compared. OS of extended lymphadenectomies (pN+, D ≥ 26, n = 273) was compared with the simulated curves. OS of patients in the following dissection intervals of negative nodes were compared: <16 (n = 233), 16-25 (n = 258), ≥26 (n = 339). RESULTS: After simulation to 26 nodes (pN+, D < 26 patients, n = 209), staging was recomputed. OS of native vs simulated early-stages (I-II) and advanced stages (III) were not different (p > 0.05). OS of patients with lymphadenectomy (≥26) was better than simulated for early and advanced stages (p = 0.008; p = 0.005). OS of patients included in distinct intervals of negative lymph nodes were different (p < 0.001). These intervals were an independent prognostic factor (multivariate analysis). CONCLUSIONS: The influence of Stage Migration was null in this set of simulations and Will Rogers phenomenon was not observed. Extended dissection performed better in OS. But the influence of the number of negative nodes, even in large dissections, was highlighted. By emphasizing the role of negative nodes, we aim to facilitate more informed decision-making in management of gastric cancer patients, ultimately leading to improved treatment outcomes and patient care.
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Adenocarcinoma , Gastrectomía , Escisión del Ganglio Linfático , Ganglios Linfáticos , Estadificación de Neoplasias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Ganglios Linfáticos/patología , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Metástasis Linfática , Tasa de SupervivenciaRESUMEN
TET enzymes (TET1-3) are dioxygenases that oxidize 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and are involved in the DNA demethylation process. In line with the observed 5hmC abundance in the brain, Tet genes are highly transcribed, with Tet3 being the predominant member. We have previously shown that Tet3 conditional deletion in the brain of male mice was associated with anxiety-like behavior and impairment in hippocampal-dependent spatial orientation. In the current study, we addressed the role of Tet3 in female mice and its impact on behavior, using in vivo conditional and inducible deletion from post-mitotic neurons. Our results indicate that conditional and inducible deletion of Tet3 in female mice increases anxiety-like behavior and impairs both spatial orientation and short-term memory. At the molecular level, we identified upregulation of immediate-early genes, particularly Npas4, in both the dorsal and ventral hippocampus and in the prefrontal cortex. This study shows that deletion of Tet3 in female mice differentially affects behavioral dimensions as opposed to Tet3 deletion in males, highlighting the importance of studying both sexes in behavioral studies. Moreover, it contributes to expand the knowledge on the role of epigenetic regulators in brain function and behavioral outcome.
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Disfunción Cognitiva , Dioxigenasas , Animales , Ansiedad/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Conducta Animal , Encéfalo/metabolismo , Disfunción Cognitiva/genética , Metilación de ADN/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Femenino , Masculino , Ratones , Neuronas/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismoRESUMEN
Plasma membrane (PM) transporters of the major facilitator superfamily (MFS) are essential for cell metabolism, growth and response to stress or drugs. In Saccharomyces cerevisiae, Jen1 is a monocarboxylate/H+ symporter that provides a model to dissect the molecular details underlying cellular expression, transport mechanism and turnover of MFS transporters. Here, we present evidence revealing novel roles of the cytosolic N- and C-termini of Jen1 in its biogenesis, PM stability and transport activity, using functional analyses of Jen1 truncations and chimeric constructs with UapA, an endocytosis-insensitive transporter of Aspergillus nidulans. Our results show that both N- and C-termini are critical for Jen1 trafficking to the PM, transport activity and endocytosis. Importantly, we provide evidence that Jen1 N- and C-termini undergo transport-dependent dynamic intramolecular interactions, which affect the transport activity and turnover of Jen1. Our results support an emerging concept where the cytoplasmic termini of PM transporters control transporter cell surface stability and function through flexible intramolecular interactions with each other. These findings might be extended to other MFS members to understand conserved and evolving mechanisms underlying transporter structure-function relationships. This article has an associated First Person interview with the first authors of the paper.
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Proteínas de Saccharomyces cerevisiae , Simportadores , Endocitosis/fisiología , Humanos , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Simportadores/metabolismoRESUMEN
Gitelman syndrome is a rare autosomal recessive inherited disease that affects the thiazidesensitive sodium-chloride cotransport channels and the magnesium channels in the distal convoluted tubule, leading to hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria. There is no cure for this condition and supportive treatment relies on ionic supplementation and symptom management. Literature regarding the anesthetic approach is scarce. This case report presents the anesthetic management of a child with Gitelman syndrome and its difficult electrolyte optimization.
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Alcalosis , Anestésicos , Síndrome de Gitelman , Hipopotasemia , Niño , Síndrome de Gitelman/complicaciones , Humanos , Hipopotasemia/tratamiento farmacológico , MagnesioRESUMEN
Plasma membrane transporters play pivotal roles in the import of nutrients, including sugars, amino acids, nucleobases, carboxylic acids, and metal ions, that surround fungal cells. The selective removal of these transporters by endocytosis is one of the most important regulatory mechanisms that ensures a rapid adaptation of cells to the changing environment (e.g., nutrient fluctuations or different stresses). At the heart of this mechanism lies a network of proteins that includes the arrestin-related trafficking adaptors (ARTs) which link the ubiquitin ligase Rsp5 to nutrient transporters and endocytic factors. Transporter conformational changes, as well as dynamic interactions between its cytosolic termini/loops and with lipids of the plasma membrane, are also critical during the endocytic process. Here, we review the current knowledge and recent findings on the molecular mechanisms involved in nutrient transporter endocytosis, both in the budding yeast Saccharomyces cerevisiae and in some species of the filamentous fungus Aspergillus. We elaborate on the physiological importance of tightly regulated endocytosis for cellular fitness under dynamic conditions found in nature and highlight how further understanding and engineering of this process is essential to maximize titer, rate and yield (TRY)-values of engineered cell factories in industrial biotechnological processes.
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Acute aortic dissection is a rare but lethal cardiac disease involving the aorta and it remains a challenge to diagnose and treat. The range of clinical features is extremely variable. Neurologic symptoms are also present in rare cases but often lead to a misdiagnosis because they mimic stroke. We report a case of a 71-year-old male with aortic dissection presented with acute onset altered mental status and left arm weakness. Aortic dissection presented with neurological symptoms is rare and requires high level of suspicion, especially in cases with unusual presentation. (AU)
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Humanos , Masculino , Anciano , Accidente Cerebrovascular , Disección Aórtica/diagnóstico , Disección Aórtica/terapia , Enfermedades del Sistema Nervioso , Resultado del TratamientoAsunto(s)
Humanos , Masculino , Anciano , Accidente Cerebrovascular , Corteza Motora , Pacientes , Mano/fisiopatologíaRESUMEN
TET3 is a member of the ten-eleven translocation (TET) family of enzymes which oxidize 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Tet3 is highly expressed in the brain, where 5hmC levels are most abundant. In adult mice, we observed that TET3 is present in mature neurons and oligodendrocytes but is absent in astrocytes. To investigate the function of TET3 in adult postmitotic neurons, we crossed Tet3 floxed mice with a neuronal Cre-expressing mouse line, Camk2a-CreERT2, obtaining a Tet3 conditional KO (cKO) mouse line. Ablation of Tet3 in adult mature neurons resulted in increased anxiety-like behavior with concomitant hypercorticalism, and impaired hippocampal-dependent spatial orientation. Transcriptome and gene-specific expression analysis of the hippocampus showed dysregulation of genes involved in glucocorticoid signaling pathway (HPA axis) in the ventral hippocampus, whereas upregulation of immediate early genes was observed in both dorsal and ventral hippocampal areas. In addition, Tet3 cKO mice exhibit increased dendritic spine maturation in the ventral CA1 hippocampal subregion. Based on these observations, we suggest that TET3 is involved in molecular alterations that govern hippocampal-dependent functions. These results reveal a critical role for epigenetic modifications in modulating brain functions, opening new insights into the molecular basis of neurological disorders.
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Ansiedad , Cognición , Dioxigenasas , Neuronas , Animales , Ansiedad/genética , Encéfalo/metabolismo , Metilación de ADN , Proteínas de Unión al ADN/genética , Dioxigenasas/genética , Dioxigenasas/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Ratones , Neuronas/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismoRESUMEN
Successful human colonizers such as Candida pathogens have evolved distinct strategies to survive and proliferate within the human host. These include sophisticated mechanisms to evade immune surveillance and adapt to constantly changing host microenvironments where nutrient limitation, pH fluctuations, oxygen deprivation, changes in temperature, or exposure to oxidative, nitrosative, and cationic stresses may occur. Here, we review the current knowledge and recent findings highlighting the remarkable ability of medically important Candida species to overcome a broad range of host-imposed constraints and how this directly affects their physiology and pathogenicity. We also consider the impact of these adaptation mechanisms on immune recognition, biofilm formation, and antifungal drug resistance, as these pathogens often exploit specific host constraints to establish a successful infection. Recent studies of adaptive responses to physiological niches have improved our understanding of the mechanisms established by fungal pathogens to evade the immune system and colonize the host, which may facilitate the design of innovative diagnostic tests and therapeutic approaches for Candida infections.
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Adaptación Fisiológica/inmunología , Antifúngicos/uso terapéutico , Candida/fisiología , Candidiasis , Farmacorresistencia Fúngica/inmunología , Interacciones Huésped-Parásitos/inmunología , Candidiasis/tratamiento farmacológico , Candidiasis/inmunología , Candidiasis/patología , HumanosRESUMEN
The article Tet3 regulates cellular identity and DNA methylation in neural progenitor cells, written by Miguel R. Branco and C. Joana Marques, was originally published electronically on the publisher's internet portal.
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Correlating data from different microscopy techniques holds the potential to discover new facets of signaling events in cellular biology. Here we report for the first time a hardware set-up capable of achieving simultaneous co-localized imaging of spatially correlated far-field super-resolution fluorescence microscopy and atomic force microscopy, a feat only obtained until now by fluorescence microscopy set-ups with spatial resolution restricted by the Abbe diffraction limit. We detail system integration and demonstrate system performance using sub-resolution fluorescent beads and applied to a test sample consisting of human bone osteosarcoma epithelial cells, with plasma membrane transporter 1 (MCT1) tagged with an enhanced green fluorescent protein (EGFP) at the N-terminal.
RESUMEN
TET enzymes oxidize 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), a process thought to be intermediary in an active DNA demethylation mechanism. Notably, 5hmC is highly abundant in the brain and in neuronal cells. Here, we interrogated the function of Tet3 in neural precursor cells (NPCs), using a stable and inducible knockdown system and an in vitro neural differentiation protocol. We show that Tet3 is upregulated during neural differentiation, whereas Tet1 is downregulated. Surprisingly, Tet3 knockdown led to a de-repression of pluripotency-associated genes such as Oct4, Nanog or Tcl1, with concomitant hypomethylation. Moreover, in Tet3 knockdown NPCs, we observed the appearance of OCT4-positive cells forming cellular aggregates, suggesting de-differentiation of the cells. Notably, Tet3 KD led to a genome-scale loss of DNA methylation and hypermethylation of a smaller number of CpGs that are located at neurogenesis-related genes and at imprinting control regions (ICRs) of Peg10, Zrsr1 and Mcts2 imprinted genes. Overall, our results suggest that TET3 is necessary to maintain silencing of pluripotency genes and consequently neural stem cell identity, possibly through regulation of DNA methylation levels in neural precursor cells.
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Diferenciación Celular/genética , Metilación de ADN/genética , Dioxigenasas/genética , Células-Madre Neurales/metabolismo , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis/genética , Encéfalo/crecimiento & desarrollo , Encéfalo/metabolismo , Proteínas de Unión al ADN/genética , Técnicas de Silenciamiento del Gen , Impresión Genómica/genética , Humanos , Ratones , Células Madre Embrionarias de Ratones/metabolismo , Neurogénesis/genética , Neuronas/metabolismo , Regiones Promotoras Genéticas/genética , Proteínas de Unión al ARN/genéticaRESUMEN
The dynamic nature of epigenetic DNA modifications is crucial for regulating gene expression in an experience-dependent manner and, thus, a potential mediator of neuronal plasticity and behavior. The discovery of the involvement of 5-hydroxymethylcytosine (5hmC) and Ten Eleven Translocation (TET) family of enzymes in the demethylation pathway uncovered a potential link between neuronal TET protein function and cognitive processes. In this review, we provide an overview on how profile of 5hmC and TET enzymes are powerful mechanisms to explain neuronal plasticity and long-term behaviors, such as cognition. More specifically, we discuss how the current knowledge integrates the function of each TET enzyme in neurophysiology and brain function.
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5-Metilcitosina/análogos & derivados , Encéfalo/fisiología , Metilación de ADN/fisiología , Dioxigenasas/fisiología , Epigénesis Genética/fisiología , Oxigenasas de Función Mixta/fisiología , Plasticidad Neuronal/fisiología , 5-Metilcitosina/fisiología , Animales , Encéfalo/enzimología , HumanosRESUMEN
Abstract Ultrasound has increasingly growing applications in anesthesia. This procedure has proven to be a novel, non-invasive and simple technique for the upper airway management, proving to be a useful tool, not only in the operating room but also in the intensive care unit and emergency department. Indeed, over the years mounting evidence has showed an increasing role of ultrasound in airway management. In this review, the authors will discuss the importance of ultrasound in the airway preoperative assessment as a way of detecting signs of difficult intubation or to define the type and/or size of the endotracheal tube as well as to help airway procedures such as endotracheal intubation, cricothyrotomy, percutaneous tracheal intubation, retrograde intubation as well as the criteria for extubation.
Resumo O uso do ultrassom em anestesia tem aumentado consideravelmente. Esse procedimento provou ser uma técnica nova, não invasiva e simples para o manejo das vias aéreas superiores, mostrou ser uma ferramenta útil não apenas em salas de cirurgia, mas também em unidades de terapia intensiva e prontos-socorros. De fato, ao longo dos anos, evidências crescentes mostraram que o papel do ultrassom no manejo das vias aéreas se destacou. Nesta revisão, discutiremos a importância da ultrassonografia na avaliação pré-operatória das vias aéreas, como forma de detectar sinais de intubação difícil ou definir o tipo e/ou tamanho do tubo endotraqueal, bem como auxiliar nos procedimentos de abordagem das vias aéreas, como intubação endotraqueal, cricotireotomia, intubação traqueal percutânea, intubação retrógrada e critérios de extubação.
Asunto(s)
Humanos , Manejo de la Vía Aérea/métodos , Cuidados Preoperatorios/métodos , Ultrasonografía , Intubación IntratraquealRESUMEN
Ultrasound has increasingly growing applications in anesthesia. This procedure has proven to be a novel, non-invasive and simple technique for the upper airway management, proving to be a useful tool, not only in the operating room but also in the intensive care unit and emergency department. Indeed, over the years mounting evidence has showed an increasing role of ultrasound in airway management. In this review, the authors will discuss the importance of ultrasound in the airway preoperative assessment as a way of detecting signs of difficult intubation or to define the type and/or size of the endotracheal tube as well as to help airway procedures such as endotracheal intubation, cricothyrotomy, percutaneous tracheal intubation, retrograde intubation as well as the criteria for extubation.
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Manejo de la Vía Aérea/métodos , Humanos , Intubación Intratraqueal , Cuidados Preoperatorios/métodos , UltrasonografíaRESUMEN
Eukaryotic α-arrestins connect environmental or stress signaling pathways to the endocytosis of plasma membrane transporters or receptors. The Saccharomyces cerevisiae lactate transporter Jen1p has been used as a model cargo for elucidating the mechanisms underlying endocytic turnover in response to carbon sources. Here, we discover a novel pathway of Jen1p endocytosis mediated by the α-arrestin Bul1p in response to the presence of cycloheximide or rapamycin, or prolonged growth in lactate. While cycloheximide or rapamycin modify cells pleiotropically, the major effect of prolonged growth in lactate was shown to be external pH alkalinization. Importantly, employment of specific inactive Jen1p versions showed that Bul1p-dependent endocytosis requires lactate transport, according to the signal imposed. Our results support a model where conformational changes of Jen1p, associated with substrate/H+ symport, are critical for the efficiency of Bul1p-dependent Jen1p turnover.
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Álcalis/farmacología , Arrestina/metabolismo , Endocitosis/fisiología , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Transporte Biológico , Membrana Celular/metabolismo , Endocitosis/efectos de los fármacos , Redes y Vías Metabólicas/efectos de los fármacos , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteínas Quinasas/metabolismo , Proteína Fosfatasa 2/metabolismo , Saccharomyces cerevisiae/crecimiento & desarrollo , Transducción de Señal/efectos de los fármacos , Simportadores/metabolismoRESUMEN
Objetivou-se avaliar qualidade do leite e do queijo Minas frescal produzido do leite de vacas alimentadas com inclusão da casca de banana seca ao sol, com ou sem adição de agentes químicos durante o processo de secagem. Foram utilizadas oito vacas F1 Holandês x Zebu, em dois quadrados latinos 4 x 4, com as seguintes dietas experimentais: dieta convencional com silagem de sorgo sem a inclusão da casca de banana (controle); dieta com inclusão da casca de banana seca ao sol em substituição de 20% da silagem de sorgo; dieta com inclusão da casca de banana seca ao sol com 2% de calcário em substituição de 20% da silagem de sorgo; dieta com inclusão da casca de banana seca ao sol com 2% de óxido de cálcio em substituição de 20% da silagem de sorgo. As amostras de leite de cada vaca foram coletadas e analisadas quanto aos teores de gordura, proteína, lactose, cinzas, sólidos totais e extrato seco desengordurado. Após esta etapa, foi realizada a elaboração de queijo Minas frescal, sendo verificados rendimento, textura, acidez titulável, pH, proteína, teor de umidade, gordura, resíduo mineral fixo, extrato seco total e realizado o teste de aceitação pelo consumidor. A composição química do leite e do queijo não apresentou influência das dietas com casca de banana. Entretanto, o rendimento ajustado para produção de queijo foi estatisticamente inferior com as dietas contendo casca de banana tratada com os aditivos químicos. Quanto à aceitação geral dos queijos pelos consumidores, não houve diferenças entre os tratamentos. Desse modo, a utilização de casca de banana seca ao sol sem aditivos químicos em substituição parcial à silagem de sorgo na dieta de vacas em lactação pode ser uma alternativa viável para produção e processamento do leite, mantendo a qualidade do produto.
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Animales , Control de Calidad , Análisis de los AlimentosRESUMEN
Fresh caught Clibanarius vittatus [SW, 31 salinity (S)] were acclimated to a dilute medium (15 S) for 10 days, employing silver staining to locate gill ion transporting tissue, immunofluorescence to localize the Na+/K+-ATPase α-subunit in the lamellae, and electron microscopy to portray ultrastructural changes in the gill epithelia. Na+/K+-ATPase activity was characterized kinetically in a gill microsomal fraction, including synergistic stimulation by NH4+ plus K+. Silver staining revealed that all 26 phyllobranchiate arthro- and pleurobranchiae participate in ion transport. Na+/K+-ATPase α-subunit staining was weak in SW crabs and distributed exclusively and irregularly within the intralamellar septal cells, particularly at the septal-pillar cell body junctions, and septal cell cytoplasm facing the hemolymph space. In 15 S crabs, α-subunit localization was intense, occupying the entire thickened septum. Pillar cells and flanges did not stain. Mitochondria and membrane foldings increased in the pillar cell flanges and intralamellar septal cells, greatly amplifying surface area. Only a single ATP binding site (VM = 130.8 ± 10.5 nmol min-1 mg protein-1; K0.5 = 55.3 ± 1.7 µmol l-1) obeying Michaelis-Menten kinetics was disclosed. Na+/K+-ATPase activity was modulated by Mg2+, Na+, and NH4+, exhibiting site-site interactions; K+ modulation showed Michaelis-Menten kinetics. K+ plus NH4+ synergistically stimulated activity ≈ 1.7-fold. Ouabain inhibited total ATPase activity by ≈ 70% (KI = 220-300 µmol l-1), revealing phosphohydrolytic activities other than the Na+/K+-ATPase. Despite ample phylogenetic separation, the phyllobranchiate lamellae of the Anomura and Caridea share many ultrastructural features, that is, an intralamellar septum and opposed abutting pillar cells, similar Na+/K+-ATPase distribution, and comparable kinetic characteristics. These findings suggest either convergent evolution at the structural and biochemical levels, or preservation of traits present in a remote common ancestor.
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Anomuros/efectos de los fármacos , Enzimas/metabolismo , Epitelio/ultraestructura , Branquias/efectos de los fármacos , Salinidad , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Animales , Anomuros/fisiología , Células Epiteliales , Branquias/fisiología , Transporte de Proteínas/efectos de los fármacos , Transporte de Proteínas/fisiología , Sodio/química , Sodio/farmacologíaRESUMEN
BACKGROUND: This study aims to evaluate the relationship between IMR (Index of Microcirculatory Resistance) and the echocardiographic evolution of left ventricular (LV) systolic and diastolic performance after ST-elevation acute myocardial infarction (STEMI), undergoing primary angioplasty (P-PCI). METHODS: IMR was evaluated immediately after P-PCI. Echocardiograms were performed within the first 24 hours (Echo1) and at 3 months (Echo2): LV volumes, ejection fraction (LVEF), wall motion score index (WMSI), E/é ratio, global longitudinal strain (GLS), and left atrial volume were measured. RESULTS: Forty STEMI patients were divided in 2 groups according to median IMR: Group 1 (IMR < 26), with less microvascular dysfunction, and Group 2 (IMR > = 26), with more microvascular dysfunction. In Echo1 GLS was significantly better in Group 1 (-14.9 vs. -12.9 in Group 2, P = 0.005). However, there were no significant differences between the two groups in LV systolic volume, LVEF and WMS. Between Echo1 and Echo2, there were significant improvements in LVEF (0.48 ± 0.06 vs. 0.55 ± 0.06, P < 0.0001), GLS (-14.9 ± 1.3 vs. -17.3 ± 7.6, P = 0.001), and E/é ratio (9.3 ± 3.4 vs. 8.2 ± 2.0, P = 0.037) in Group 1, but not in Group 2: LVEF (0.49 ± 0.06 vs. 0.50 ± 0.05, P = 0.47), GLS (-12.9 ± 2.4 vs. -14.4 ± 3.2, P = 0.052), and E/é ratio (8.8 ± 2.4 vs. 10.0 ± 4.7, P = 0.18). WMSI improved significantly more in Group 1 (reduction of -17.1% vs. -6.8% in Group 2, P = 0.015). CONCLUSION: Lower IMR was associated with better myocardial GLS acutely after STEMI, and with a significantly higher recovery of the LVEF, WMSI, E/E' ratio and GLS, suggesting that IMR is an early marker of cardiac recovery, after acute myocardial infarction.
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Ecocardiografía/métodos , Ventrículos Cardíacos/fisiopatología , Microcirculación/fisiología , Infarto del Miocardio/fisiopatología , Función Ventricular Izquierda/fisiología , Adulto , Anciano , Angioplastia/métodos , Biomarcadores , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/cirugía , Estudios ProspectivosRESUMEN
Epigenetic modifications of the genome play important roles in controlling gene transcription thus regulating several molecular and cellular processes. A novel epigenetic modification - 5-hydroxymethylcytosine (5hmC) - has been recently described and attracted a lot of attention due to its possible involvement in the active DNA demethylation mechanism. TET enzymes are dioxygenases capable of oxidizing the methyl group of 5-methylcytosines (5mC) and thus converting 5mC into 5hmC. Although most of the work on TET enzymes and 5hmC has been carried out in embryonic stem (ES) cells, the highest levels of 5hmC occur in the brain and in neurons, pointing to a role for this epigenetic modification in the control of neuronal differentiation, neural plasticity and brain functions. Here we review the most recent advances on the role of TET enzymes and DNA hydroxymethylation in neuronal differentiation and function.