RESUMO
Heterochromatin stability is crucial for progenitor proliferation during early neurogenesis. It relays on the maintenance of local hubs of H3K9me. However, understanding the formation of efficient localized levels of H3K9me remains limited. To address this question, we used neural stem cells to analyze the function of the H3K9me2 demethylase PHF2, which is crucial for progenitor proliferation. Through mass-spectroscopy and genome-wide assays, we show that PHF2 interacts with heterochromatin components and is enriched at pericentromeric heterochromatin (PcH) boundaries where it maintains transcriptional activity. This binding is essential for silencing the satellite repeats, preventing DNA damage and genome instability. PHF2's depletion increases the transcription of heterochromatic repeats, accompanied by a decrease in H3K9me3 levels and alterations in PcH organization. We further show that PHF2's PHD and catalytic domains are crucial for maintaining PcH stability, thereby safeguarding genome integrity. These results highlight the multifaceted nature of PHF2's functions in maintaining heterochromatin stability and regulating gene expression during neural development. Our study unravels the intricate relationship between heterochromatin stability and progenitor proliferation during mammalian neurogenesis.
Assuntos
Proliferação de Células , Heterocromatina , Histonas , Células-Tronco Neurais , Neurogênese , Animais , Humanos , Camundongos , Instabilidade Genômica , Heterocromatina/metabolismo , Heterocromatina/genética , Histona Desmetilases/metabolismo , Histona Desmetilases/genética , Histonas/metabolismo , Metilação , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologiaRESUMO
The Jumonji-C (JmjC) family of lysine demethylases (KDMs) (JMJC-KDMs) plays an essential role in controlling gene expression and chromatin structure. In most cases, their function has been attributed to the demethylase activity. However, accumulating evidence demonstrates that these proteins play roles distinct from histone demethylation. This raises the possibility that they might share domains that contribute to their functional outcome. Here, we show that the JMJC-KDMs contain low-complexity domains and intrinsically disordered regions (IDR), which in some cases reached 70% of the protein. Our data revealed that plant homeodomain finger protein (PHF2), KDM2A, and KDM4B cluster by phase separation. Moreover, our molecular analysis implies that PHF2 IDR contributes to transcription regulation. These data suggest that clustering via phase separation is a common feature that JMJC-KDMs utilize to facilitate their functional responses. Our study uncovers a novel potential function for the JMJC-KDM family that sheds light on the mechanisms to achieve the competent concentration of molecules in time and space within the cell nucleus.
Assuntos
Histona Desmetilases , Histona Desmetilases com o Domínio Jumonji , Núcleo Celular/metabolismo , Desmetilação , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Lisina/metabolismoRESUMO
Modulation of Alzheimer's disease (AD) risk begins early in life. During embryo development and postnatal maturation, the brain receives maternal physiological influences and establishes epigenetic patterns that build its level of resilience to late-life diseases. The soluble epoxide hydrolase inhibitor N-[1-(1-oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy)phenyl] urea (TPPU), reported as ant-inflammatory and neuroprotective against AD pathology in the adult 5XFAD mouse model of AD, was administered to wild-type (WT) female mice mated to heterozygous 5XFAD males during gestation and lactation. Two-month-old 5XFAD male and female offspring of vehicle-treated dams showed memory loss as expected. Remarkably, maternal treatment with TPPU fully prevented memory loss in 5XFAD. TPPU-induced brain epigenetic changes in both WT and 5XFAD mice, modulating global DNA methylation (5-mC) and hydroxymethylation (5-hmC) and reducing the gene expression of some histone deacetylase enzymes (Hdac1 and Hdac2), might be on the basis of the long-term neuroprotection against cognitive impairment and neurodegeneration. In the neuropathological analysis, both WT and 5XFAD offspring of TPPU-treated dams showed lower levels of AD biomarkers of tau hyperphosphorylation and microglia activation (Trem2) than the offspring of vehicle-treated dams. Regarding sex differences, males and females were similarly protected by maternal TPPU, but females showed higher levels of AD risk markers of gliosis and neurodegeneration. Taken together, our results reveal that maternal treatment with TPPU impacts in preventing or delaying memory loss and AD pathology by inducing long-term modifications in the epigenetic machinery and its marks.
Assuntos
Doença de Alzheimer , Animais , Camundongos , Feminino , Masculino , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Epóxido Hidrolases/metabolismo , Encéfalo/metabolismo , Modelos Animais de Doenças , Transtornos da Memória/patologia , Camundongos Transgênicos , Glicoproteínas de Membrana/metabolismo , Receptores Imunológicos/metabolismoRESUMO
The decrease in the cost of sensors during the last years, and the arrival of the 5th generation of mobile technology will greatly benefit Internet of Things (IoT) innovation. Accordingly, the use of IoT in new agronomic practices might be a vital part for improving soil quality, optimising water usage, or improving the environment. Nonetheless, the implementation of IoT systems to foster environmental awareness in educational settings is still unexplored. This work addresses the educational need to train students on how to design complex sensor-based IoT ecosystems. Hence, a Project-Based-Learning approach is followed to explore multidisciplinary learning processes implementing IoT systems that varied in the sensors, actuators, microcontrollers, plants, soils and irrigation system they used. Three different types of planters were implemented, namely, hydroponic system, vertical garden, and rectangular planters. This work presents three key contributions that might help to improve teaching and learning processes. First, a holistic architecture describing how IoT ecosystems can be implemented in higher education settings is presented. Second, the results of an evaluation exploring teamwork performance in multidisciplinary groups is reported. Third, alternative initiatives to promote environmental awareness in educational contexts (based on the lessons learned) are suggested. The results of the evaluation show that multidisciplinary work including students from different expertise areas is highly beneficial for learning as well as on the perception of quality of the work obtained by the whole group. These conclusions rekindle the need to encourage work in multidisciplinary teams to train engineers for Industry 4.0 in Higher Education.
Assuntos
Ecossistema , Internet , Internet das CoisasRESUMO
Parasites release extracellular vesicles (EVs) which, in some cases, modulate the host's immune response contributing to the establishment of the infection. In this work we have isolated and characterized the EVs released by trophozoites of the human protozoan parasite Entamoeba histolytica, the causal agent of amoebiasis, when alone or in coculture with human neutrophils, and determined their effect on neutrophil NETs and ROS production. Nanoparticle tracking analysis showed that amoebic EVs are variable in size, ranging from less than 50 nm to nearly 600 nm in diameter (average of 167 nm), whereas neutrophil EVs are more uniform in size, with an average of 136 nm. In cocultures amoeba:neutrophil (1:100) most EVs are 98 nm in size, which is the typical size of exosomes. EVs from amoebae and neutrophils showed almost equal levels of ROS, which were considerably increased in EVs from cocultures. Uptake of amoebic EVs by neutrophils was demonstrated by fluorescence and resulted in a significant reduction in the oxidative burst and NET release triggered by PMA, ionophore A23187, or the amoebae itself used as stimuli. Interestingly, uptake of EVs from cocultures did not affect ROS production, but instead caused a greater delay in the onset of NETs release and in their quantity. A comparative proteomic analysis between the EVs of amoebae and neutrophils separately vs the cocultures showed a similar distribution of protein categories in the GO analysis, but differences in the expression and abundance of proteins such as the N-acetyl-D-galactosamine (GalNAc) inhibitable surface lectin and calreticulin in amoeba EVs, and various antimicrobial molecules in neutrophil EVs, such as lactoferrin and myeloperoxidase. These results highlight the importance of EVs in the immunomodulatory effects exerted by amoeba on human neutrophils.
Assuntos
Entamoeba histolytica , Vesículas Extracelulares , Animais , Humanos , Entamoeba histolytica/metabolismo , Neutrófilos , Explosão Respiratória , Trofozoítos , Espécies Reativas de Oxigênio/metabolismo , Proteômica , Vesículas Extracelulares/metabolismo , ImunidadeRESUMO
Monomeric C-reactive protein (mCRP), the activated isoform of CRP, induces tissue damage in a range of inflammatory pathologies. Its detection in infarcted human brain tissue and its experimentally proven ability to promote dementia with Alzheimer's disease (AD) traits at 4 weeks after intrahippocampal injection in mice have suggested that it may contribute to the development of AD after cerebrovascular injury. Here, we showed that a single hippocampal administration of mCRP in mice induced memory loss, lasting at least 6 months, along with neurodegenerative changes detected by increased levels of hyperphosphorylated tau protein and a decrease of the neuroplasticity marker Egr1. Furthermore, co-treatment with the monoclonal antibody 8C10 specific for mCRP showed that long-term memory loss and tau pathology were entirely avoided by early blockade of mCRP. Notably, 8C10 mitigated Egr1 decrease in the mouse hippocampus. 8C10 also protected against mCRP-induced inflammatory pathways in a microglial cell line, as shown by the prevention of increased generation of nitric oxide. Additional in vivo and in vitro neuroprotective testing with the anti-inflammatory agent TPPU, an inhibitor of the soluble epoxide hydrolase enzyme, confirmed the predominant involvement of neuroinflammatory processes in the dementia induced by mCRP. Therefore, locally deposited mCRP in the infarcted brain may be a novel biomarker for AD prognosis, and its antibody blockade opens up therapeutic opportunities for reducing post-stroke AD risk.
RESUMO
Blackfordia virginica is an important hydromedusae in the zooplankton of coastal lagoons at Mexico. In order to contribute to their study, morphological variations of these species were analyzed in the system of coastal lagoons of Chiapas, Mexico. A total of 503 jellyfish were studied their sizes varied from 6.1 to 9.9 mm of umbrelar diameter. The number of marginal tentacles varied from 86 to 125. A 67.7% females and 30.2% males were recognized. Only 31 jellyfish (26 females and five males) presented morphological variations of ten different types and affected the number and form of the handles, radial channels and gonads. The size of the jellyfish and the number of tentacles reflected a correlation of 0.74.
Assuntos
Hidrozoários/anatomia & histologia , Animais , Feminino , Água Doce , Hidrozoários/classificação , Masculino , MéxicoRESUMO
Observations on microplankton in the autumn of 1996 revealed the existence of high densities of Pseudo-nitzschia spp. A similar phenomenon was found in November 1998 and November 1999 and a month later it shifted to the southern Mazatlán Bay while in California, USA, incidents of the poisoning of sea mammals were being recorded; this also happened on the Mexican Pacific coasts from January to March. Water samples collected at surface (<0.5 m deep) and subsurface (10 m deep) monthly, from November 1998 to January 1999 and every week from February 1999 to May 2000, were analyzed by the Utermöhl technique at 400 enlargements. Phytoplankton quantification showed winter and summer pulses; the 1998-1999 period was higher than the 1999-2000 period. Five species of Pseudo-nitzschia were identified by electron microscopy (TEM and SEM); a new study has revealed other species. High values of Pseudo-nitzschia were observed: 730 P-n/ml (Dec. 1999), 610 P-n/ml (Dec. 1998), 335 P-n/ml (Jul. 1999), 198 P-n/ml (Feb. 1999), 170 P-n/ml (Nov. 1998), 123 P-n/ml (Mar. 1999), 108 P-n/ml (Aug. 1999). The blooms of other species of diatoms (Thalassiosira spp., Asterionellopsis glacialis, Chaetoceros spp., Skeletonema costatum), dinoflagellates (Prorocentrum spp., Scripsiella trochoidea) and ciliates (Myrionecta rubra) were also observed.
Assuntos
Diatomáceas/ultraestrutura , Monitoramento Ambiental , Eutrofização/fisiologia , Fitoplâncton/ultraestrutura , Água do Mar , Animais , Diatomáceas/classificação , Dinoflagellida/classificação , Dinoflagellida/ultraestrutura , México , Fitoplâncton/classificação , Densidade Demográfica , Estações do AnoRESUMO
Blackfordia virginica is an important hydromedusae in the zooplankton of coastal lagoons at Mexico. In order to contribute to their study, morphological variations of these species were analyzed in the system of coastal lagoons of Chiapas, Mexico. A total of 503 jellyfish were studied their sizes varied from 6.1 to 9.9 mm of umbrelar diameter. The number of marginal tentacles varied from 86 to 125. A 67.7% females and 30.2% males were recognized. Only 31 jellyfish (26 females and five males) presented morphological variations of ten different types and affected the number and form of the handles, radial channels and gonads. The size of the jellyfish and the number of tentacles reflected a correlation of 0.74.
Assuntos
Animais , Masculino , Feminino , Hidrozoários , Água Doce , Hidrozoários , MéxicoRESUMO
Observaciones previas sobre el microplancton de la Bahía de Mazatlán, en el otoño de 1996, revelaron la existencia de altas densidades de Pseudo-nitzschia spp. Este mismo fenómeno se encontró en noviembre 1998 y un mes después se había desplazado al sur de la Bahía de Mazatlán, mientras que por esas mismas fechas, en California, EUA, se registraban accidentes de envenenamiento de mamíferos marinos, accidentes que en el noroeste de México se aprecian entre enero y marzo. Mensualmente se recolectaron muestras de agua superficial (< 0.5 m) y subsuperficial (10 m), de noviembre 1998 a enero 1999 y cada semana, entre febrero 1999 y mayo 2000; las muestras fueron analizadas por la técnica de Utermöhl a 400X. La cuantificación del microplancton presentó un amplio pulso invernal y otro menor en verano de cada ciclo anual. Con el empleo de microscopio electrónico (MEB y MET), se reconocieron cuatro especies de Pseudo-nitzschia y una más en estudio reciente. Las densidades de Pseudo-nitzschia fueron, en orden de importancia: 760 céls ml-1 (7 dic.1999), 610 (6 dic.1998), 335 (12 jul.1999), 198 (1º. feb. 1999), 170 (6 nov.1998), 123 (17 mar.1999), 108 (11 ago.1999). Otras especies de diatomeas (Thalassiosira spp., Asterionellopsis glacialis, Chaetoceros spp., Skeletonema costatum), dinoflagelados (Prorocentrum spp., Scripsiella trochoideda) y ciliados (Myrionecta rubra), manifestaron proliferaciones altas durante el período de este estudio
Observations on microplankton in the autumn of 1996 revealed the existence of high densities of Pseudo-nitzschia spp. A similar phenomenon was found in November 1998 and November 1999 and a month later it shifted to the southern Mazatlán Bay while in California, USA, incidents of the poisoning of sea mammals were being recorded; this also happened on the Mexican Pacific coasts from January to March. Water samples collected at surface (<0.5 m deep) and subsurface (10 m deep) monthly, from November 1998 to January 1999 and every week from February 1999 to May 2000, were analyzed by the Utermöhl technique at 400 enlargements. Phytoplankton quantification showed winter and summer pulses; the 1998-1999 period was higher than the 1999-2000 period. Five species of Pseudo-nitzschia were identified by electron microscopy (TEM and SEM); a new study has revealed other species. High values of Pseudo-nitzschia were observed: 730 P-n/ml (Dec. 1999), 610 P-n/ml (Dec. 1998), 335 P-n/ml (Jul. 1999), 198 P-n/ml (Feb. 1999), 170 P-n/ml (Nov. 1998), 123 P-n/ml (Mar. 1999), 108 P-n/ml (Aug. 1999). The blooms of other species of diatoms (Thalassiosira spp., Asterionellopsis glacialis, Chaetoceros spp., Skeletonema costatum), dinoflagellates (Prorocentrum spp., Scripsiella trochoidea) and ciliates (Myrionecta rubra) were also observed
Assuntos
Animais , Diatomáceas/ultraestrutura , Monitoramento Ambiental , Eutrofização/fisiologia , Fitoplâncton/ultraestrutura , Água do Mar/química , Diatomáceas/classificação , Dinoflagellida/classificação , Dinoflagellida/ultraestrutura , México , Densidade Demográfica , Fitoplâncton/classificação , Estações do AnoRESUMO
Introducción. Las consecuencias del embarazo en adolescentes abarcan aspectos maternos y fetales físicos, además de psicosociales que interfieren en la madurez y aceptación sociofamiliar de la madre y en la salud del producto. En este estudio se presentan las características sociales, la actitud materna y la morbilidad materno-infantil de un grupo de madres menores de 18 años. Material y métodos. Se aplicó una encuesta descriptiva a 499 madres adolescentes de 12 a 18 años de edad, en relación con los factores psicosociales que condicionan el embarazo y la morbilidad materno-infantil. Esta encuesta fue diseñada por un grupo multidisciplinario en la atención integral del adolescente y constó de: ficha de identificación, 10 reactivos sobre características sociofamiliares y 9 sobre el seguimiento médico de la madre y el producto. Aplicándose en el último trimestre del embarazo y durante el puerperio inmediato. Los reactivos sobre salud materno-fetal fueron llenados por el obstetra y el pediatra que atendieron a la madre y al recién nacido. Resultados. Entre los hallazgos encontrados se mencionan: madres solteras 29 por ciento, en unión libre 48 por ciento y con matrimonio civil 27 por ciento. Fracaso escolar antes del embarazo en 74 por ciento de ellas, con ingresos económicos menores al salario mínimo en 77 por ciento. Un 25 por ciento de las embarazadas tuvieron control médico prenatal insuficiente, que se correlacionó con 25 por ciento de morbilidad materna relacionada con el embarazo y 19 por ciento de patología de feto y del recién nacido. Las enfermedades maternas más frecuentes fueron las infecciones cervicovaginales, caries dentales e infecciones de vías urinarias. En el recién nacido las enfermedades más comunes fueron: hipoxia perinatal, prematurez y desnutrición en útero. Conclusión. El embarazo en adolescentes y acciones educativas y previativas para disminuir la frecuencia de relaciones coitales desprotegidas, que dan como resultado embarazos no deseados y enfermedades de transmisión sexual