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1.
Ying Yong Sheng Tai Xue Bao ; 35(2): 371-380, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38523094

RESUMEN

To elucidate the spatial patterns of understory species in fragmented forests adjacent to human settlements, we examined the spatial distribution and intraspecific correlations of three dominant species Mallotus philippensis, Dasymashalon trichophorum, and Psychotria rubra by employing point pattern analysis, which were the top three in terms of importance value in the shrub layer of Fengshui forest in Leizhou Peninsula, Guangdong. The results showed that all the three species were mainly aggregated at the scale of 0-25 m, especially for young trees. The degree of aggregation gradually diminished with increasing age class. The spatial distribution patterns of three species were predominantly influenced by habitat heterogeneity, negative density dependence, and dispersal limitation. They showed positive association among different age classes, especially between young trees and middle age trees and between young trees and adult trees. Therefore, in the ecological restoration process of Leizhou Peninsula, M. philippensis, D. trichophorum, and P. rubra should be planted in clusters at a small scale within the range of 0-25 m, with the degree of clusters depending on plant morphology. For larger scales, a dispersed cultivation approach was advocated.


Asunto(s)
Bosques , Árboles , Humanos , Ecosistema , China , Plantas
2.
Biol Psychiatry ; 94(5): 367-377, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-36906500

RESUMEN

BACKGROUND: The ability of neurons to respond to external stimuli involves adaptations of gene expression. Induction of the transcription factor ΔFOSB in the nucleus accumbens, a key brain reward region, is important for the development of drug addiction. However, a comprehensive map of ΔFOSB's gene targets has not yet been generated. METHODS: We used CUT&RUN (cleavage under targets and release using nuclease) to map the genome-wide changes in ΔFOSB binding in the 2 main types of nucleus accumbens neurons-D1 or D2 medium spiny neurons-after chronic cocaine exposure. To annotate genomic regions of ΔFOSB binding sites, we also examined the distributions of several histone modifications. Resulting datasets were leveraged for multiple bioinformatic analyses. RESULTS: The majority of ΔFOSB peaks occur outside promoter regions, including intergenic regions, and are surrounded by epigenetic marks indicative of active enhancers. BRG1, the core subunit of the SWI/SNF chromatin remodeling complex, overlaps with ΔFOSB peaks, a finding consistent with earlier studies of ΔFOSB's interacting proteins. Chronic cocaine use induces broad changes in ΔFOSB binding in both D1 and D2 nucleus accumbens medium spiny neurons of male and female mice. In addition, in silico analyses predict that ΔFOSB cooperatively regulates gene expression with homeobox and T-box transcription factors. CONCLUSIONS: These novel findings uncover key elements of ΔFOSB's molecular mechanisms in transcriptional regulation at baseline and in response to chronic cocaine exposure. Further characterization of ΔFOSB's collaborative transcriptional and chromatin partners specifically in D1 and D2 medium spiny neurons will reveal a broader picture of the function of ΔFOSB and the molecular basis of drug addiction.


Asunto(s)
Trastornos Relacionados con Cocaína , Cocaína , Ratones , Masculino , Femenino , Animales , Cocaína/farmacología , Cocaína/metabolismo , Ratones Transgénicos , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Núcleo Accumbens/metabolismo , Ratones Endogámicos C57BL
4.
Mar Pollut Bull ; 186: 114425, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36462424

RESUMEN

A 1-year field monitoring program was carried out to observe seasonal variation in N2O fluxes at two typical mangrove wetlands in a subtropical estuary. The soils in the island-type mangrove wetland had a higher level of heavy metal(loid) contamination and a lower level of salinity compared to the small bay-type mangrove wetland. While there was a high level of similarity in the seasonal variation pattern of N2O fluxes between the two investigated sites with both being significantly higher in summer than in other seasons, the average of N2O fluxes in the island-type mangrove wetland was 7.19 µg·m-2·h-1, which tended to be lower compared to the small bay-type mangrove wetland (15.63 µg·m-2·h-1). Overall, N2O flux was closely related to soil-borne heavy metal(loid)s, showing a trend to decrease with increasing concentration of these heavy metal(loid)s. The N2O fluxes increased with decreasing abundance of either denitrifiers or nitrifiers. But the opposite was observed for the anammox bacteria present in the soils. The anammox bacteria were more sensitive to heavy metal(loid) stress but more tolerated high salinity encountered in the investigated soils compared to the denitrifiers or nitrifiers. It appears that anammox reactions mediated by anammox bacteria played a key role in affecting the spatial variation in N2O fluxes from the mangrove soils in the study area. And an increased level of ammonium in soils tended to promote the activity of anammox bacteria and consequently enhanced N2O emission from the mangrove soils.


Asunto(s)
Estuarios , Metales Pesados , Humedales , Contaminación Ambiental , Suelo , Óxido Nitroso/análisis
5.
Environ Sci Pollut Res Int ; 29(19): 28933-28945, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34988785

RESUMEN

It is important to investigate the airborne bacterial air quality in urban forest parks as tree bacteriostasis practices are being increasingly advocated as measures to improve the air quality and public health in urban green spaces around the world. The aim of the study was to quantitatively investigate airborne culturable bacteria (ACB) concentration levels based on field measurements in every season in five selected forest communities and the uncovered space in an urban forest park, as well as the effects of several factors on the culturability of airborne bacteria. Results suggested that the airborne bacterial levels of all the forest communities reached the clean air quality standard with regard to the airborne bacteria content, with the highest concentration of ACB showing in the uncovered space (1658 ± 1298 CFU/m3) and the lowest showing in the mixed community (907 ± 567 CFU/m3). The temporal distribution analysis showed that the airborne bacteria were mostly concentrated in summer, as well as in the morning and afternoon. The bacteriostatic rates of the mixed community were significantly different with seasonal variation (p < 0.05). Spearman's correlations revealed that the concentration of ACB was significantly positively correlated with the season, wind speed (WS), temperature (T), ultraviolet light (UV), negative air ion (NAI), and total suspended particles (TSP) (p<0.05) but significantly negatively correlated with the forest community type (p < 0.05). Overall, the selection of tree species plays a key role in shaping the forest structure and improving air quality, and the urban forest highlights key priorities for future efforts toward a cleaner, healthier, and more diverse regional forest environment.


Asunto(s)
Microbiología del Aire , Parques Recreativos , Bacterias , China , Monitoreo del Ambiente/métodos , Bosques , Estaciones del Año , Árboles
6.
J Environ Manage ; 304: 114225, 2022 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-34871870

RESUMEN

Estimating the recreational value of a coastal wetland park is useful in understanding wetland ecosystem and nurturing a balanced relationship between wetland tourism exploration and natural conservation. This study aims to apply appropriate methodologies to accurately estimate the recreational value of a coastal wetland park. The Nansha Wetland in China was used as the study site, and its recreational value was divided into non-use value (estimated using the choice experiment method (CEM)) and use value (estimated using travel cost interval analysis (TCIA)). The data were collected via questionnaires consisting of different choice experiment scenarios and travel cost investigations. The results showed that the per capita and total non-use values were 116.97 CNY/17.80 USD and 24.56 million CNY/3.74 million USD, respectively, and the per capita and total use values were 313.95 CNY/47.79 USD and 65.93 million CNY/10.04 million USD. Therefore, the per capita and total recreational values were 430.92 CNY/65.59 USD and 90.49 million CNY/13.77 million USD. CEM was used to identify tourists' trade-offs and preferences among the selected wetland attributes. As a result, tourists were found to have the largest marginal willingness to pay (MWTP) for "mangrove coverage," followed by "species of rare birds" and "water visibility." TCIA was used to solve the under-dispersion problem of the number of trips. Based on these findings, several managerial implications were identified, including adjusting ticket price based on the non-use value, regulating tourists' behaviors, enhancing the protection of mangroves, improving the water quality and the living habitats of migrant birds, and promoting science education and popularization.


Asunto(s)
Ecosistema , Humedales , Conservación de los Recursos Naturales , Costos y Análisis de Costo , Parques Recreativos , Viaje
7.
Neuron ; 109(18): 2943-2966.e8, 2021 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-34480866

RESUMEN

Neuronal alternative splicing is a key gene regulatory mechanism in the brain. However, the spliceosome machinery is insufficient to fully specify splicing complexity. In considering the role of the epigenome in activity-dependent alternative splicing, we and others find the histone modification H3K36me3 to be a putative splicing regulator. In this study, we found that mouse cocaine self-administration caused widespread differential alternative splicing, concomitant with the enrichment of H3K36me3 at differentially spliced junctions. Importantly, only targeted epigenetic editing can distinguish between a direct role of H3K36me3 in splicing and an indirect role via regulation of splice factor expression elsewhere on the genome. We targeted Srsf11, which was both alternatively spliced and H3K36me3 enriched in the brain following cocaine self-administration. Epigenetic editing of H3K36me3 at Srsf11 was sufficient to drive its alternative splicing and enhanced cocaine self-administration, establishing the direct causal relevance of H3K36me3 to alternative splicing of Srsf11 and to reward behavior.


Asunto(s)
Empalme Alternativo/fisiología , Conducta Adictiva/metabolismo , Cromatina/metabolismo , Cocaína/administración & dosificación , Inhibidores de Captación de Dopamina/administración & dosificación , Recompensa , Empalme Alternativo/efectos de los fármacos , Animales , Conducta Adictiva/genética , Conducta Adictiva/psicología , Cromatina/genética , Epigénesis Genética/efectos de los fármacos , Epigénesis Genética/fisiología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Autoadministración
8.
Chemosphere ; 269: 128735, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33127108

RESUMEN

Mangrove plays an important role in modulating global warming through substantial blue carbon storage relative to their greenhouse gas emission potential. The presence of heavy metals in mangrove wetlands can influence soil microbial communities with implications for decomposition of soil organic matter and emission of greenhouse gases. In this study, field monitoring and a microcosm experiment were conducted to examine the impacts of heavy metal pollution on soil microbial communities and greenhouse gas fluxes. The results show that heavy metal pollution decreased the richness and diversity of the overall soil microbial functional groups (heterotrophs and lithotrophs); however, it did not inhibit the activities of the methanogenic communities, possibly due to their stronger tolerance to heavy metal toxicity compared to the broader soil microbial communities. Consequently, the presence of heavy metals in the mangrove soils significantly increased the emission of CH4 while the emission of CO2 as a proxy of soil microbial respiration was decreased. The soil organic carbon content could also buffer the effect of heavy metal pollution and influence CO2 emissions due to reduced toxicity to microbes. The findings have implications for understanding the complication of greenhouse gas emissions by heavy metal pollution in mangrove wetlands.


Asunto(s)
Metales Pesados , Humedales , Carbono , Dióxido de Carbono/análisis , Monitoreo del Ambiente , Metales Pesados/toxicidad , Metano/análisis , Óxido Nitroso/análisis , Suelo , Microbiología del Suelo
9.
Huan Jing Ke Xue ; 41(5): 2496-2504, 2020 May 08.
Artículo en Chino | MEDLINE | ID: mdl-32608869

RESUMEN

Wetlands play an important role in maintaining ecosystem functions. Wetlands in China have suffered intensive human disturbance, especially before 2000, resulting in great losses and degradation. Therefore, two national wetland resource surveys were carried out by the Chinese government during 1998-2003 and 2008-2013 to determine the status of wetlands, understand their dynamics, and provide substantial data that can aid scientific wetland conservation. Based on the survey data, the spatial pattern and spatial autocorrelation were explored using the standard deviation ellipse as well as global and local spatial autocorrelation statistics. GIS mapping was employed to display the results via the visualization of the spatial patterns and relationships. Results indicate that:① Changes in the wetlands of China are significant and exhibit obvious regional differences. The center of the ellipse of the total wetlands has moved to the west, and the degree of spatial differentiation between natural wetlands and artificial wetlands is increasing. There is no significant spatial autocorrelation for changes in artificial wetlands. ② The changes in natural wetlands are significantly spatially autocorrelated and clustered, which are identified by global Moran's I and local Moran's I. The hotspots of natural wetland change are concentrated primarily in Qinghai, Tibet, and Sichuan. The individual hotspot is in Inner Mongolia and the cold spot is in Henan. The difference in spatial autocorrelation between natural and artificial wetland changes indicates that natural wetland changes have shown spatial continuity, while artificial wetland changes have shown strong spatial randomness. ③ Some useful spatial associations are used to delineate wetland conservation effects. Then, three major or five minor effective protection management regions are identified. Wetland conservation efforts should be continuously strengthened and improved, especially in the middle-lower Yangtze River region of central China. The use of Moran statistics helps to reveal spatial autocorrelation and identify the conservation effects in wetland changes, which can provide a basis for decision-making in regional wetland conservation and management systems.


Asunto(s)
Ecosistema , Humedales , China , Conservación de los Recursos Naturales , Humanos , Tibet
10.
Biol Psychiatry ; 88(7): 566-575, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32600739

RESUMEN

BACKGROUND: Stress exacerbates symptoms of schizophrenia and attention-deficit/hyperactivity disorder, which are characterized by impairments in sustained attention. Yet how stress regulates attention remains largely unexplored. We investigated whether a 6-day variable stressor altered sustained attention and the cholinergic attention system in male and female rats. METHODS: Sustained attention was tested with the sustained attention task. Successful performance on the sustained attention task relies on the release of acetylcholine (ACh) into the cortex from cholinergic neurons in the nucleus basalis of Meynert (NBM). Thus, we evaluated whether variable stress (VS) altered the morphology of these neurons with a novel approach using a Cre-dependent virus in genetically modified ChAT::Cre rats, a species used for this manipulation only. Next, electrochemical recordings measured cortical ACh following VS. Finally, we used RNA sequencing to identify VS-induced transcriptional changes in the NBM. RESULTS: VS impaired attentional performance in the sustained attention task and increased the dendritic complexity of NBM cholinergic neurons in both sexes. NBM cholinergic neurons are mainly under inhibitory control, so this morphological change could increase inhibition on these neurons, reducing downstream ACh release to impair attention. Indeed, VS decreased ACh release in the prefrontal cortex of male rats. Quantification of global transcriptional changes revealed that although VS induced many sex-specific changes in gene expression, it increased several signaling molecules in both sexes. CONCLUSIONS: These studies suggest that VS impairs attention by inducing molecular and morphological changes in the NBM. Identifying mechanisms by which stress regulates attention may guide the development of novel treatments for psychiatric disorders with attention deficits.


Asunto(s)
Núcleo Basal de Meynert , Colina O-Acetiltransferasa , Acetilcolina , Animales , Núcleo Basal de Meynert/metabolismo , Colina O-Acetiltransferasa/metabolismo , Colinérgicos , Neuronas Colinérgicas , Femenino , Masculino , Ratas
11.
Curr Opin Neurobiol ; 59: 26-33, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31015104

RESUMEN

A wealth of studies in the mammalian nervous system indicate the role of epigenetic gene regulation in both basic neurobiological function and disease. However, the relationship between epigenetic regulation and neuropathology is largely correlational due to the presence of mixed cell populations within brain regions and the genome-wide effects of classical approaches to manipulate the epigenome. Locus-specific epigenetic editing allows direct epigenetic regulation of specific genes to elucidate the direct causal relationship between epigenetic modifications and transcription. This review discusses some of the latest innovations in the efficacy and flexibility in this approach that hold promise for neurobiological application.


Asunto(s)
Edición Génica , Enfermedades del Sistema Nervioso , Animales , Epigénesis Genética , Regulación de la Expresión Génica , Genoma
12.
J Neurosci ; 38(19): 4569-4583, 2018 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-29654189

RESUMEN

Cognitive decline is a debilitating hallmark during preclinical stages of Alzheimer's disease (AD), yet the causes remain unclear. Because histone acetylation homeostasis is critical for mediating epigenetic gene control throughout neuronal development, we postulated that its misregulation contributes to cognitive impairment preceding AD pathology. Here, we show that disruption of Tip60 histone acetlytransferase (HAT)/histone deacetylase 2 (HDAC2) homeostasis occurs early in the brain of an AD-associated amyloid precursor protein (APP) Drosophila model and triggers epigenetic repression of neuroplasticity genes well before Aß plaques form in male and female larvae. Repressed genes display enhanced HDAC2 binding and reduced Tip60 and histone acetylation enrichment. Increasing Tip60 in the AD-associated APP brain restores Tip60 HAT/HDAC2 balance by decreasing HDAC2 levels, reverses neuroepigenetic alterations to activate synaptic plasticity genes, and reinstates brain morphology and cognition. Such Drosophila neuroplasticity gene epigenetic signatures are conserved in male and female mouse hippocampus and their expression and Tip60 function is compromised in hippocampus from AD patients. We suggest that Tip60 HAT/HDAC2-mediated epigenetic gene disruption is a critical initial step in AD that is reversed by restoring Tip60 in the brain.SIGNIFICANCE STATEMENT Mild cognitive impairment is a debilitating hallmark during preclinical stages of Alzheimer's disease (AD), yet its causes remain unclear. Although recent findings support elevated histone deacetylase 2 (HDAC2) as a cause for epigenetic repression of synaptic genes that contribute to cognitive deficits, whether alterations in histone acetlytransferase (HAT) levels that counterbalance HDAC2 repressor action occur and the identity of these HATs remain unknown. We demonstrate that disruption of Tip60 HAT/HDAC2 homeostasis occurs early in the AD Drosophila brain and triggers epigenetic repression of neuroplasticity genes before Aß plaques form. Increasing Tip60 in the AD brain restores Tip60 HAT/HDAC2 balance, reverses neuroepigenetic alterations to activate synaptic genes, and reinstates brain morphology and cognition. Our data suggest that disruption of the Tip60 HAT/HDAC2 balance is a critical initial step in AD.


Asunto(s)
Trastornos del Conocimiento/genética , Trastornos del Conocimiento/terapia , Represión Epigenética/genética , Histona Desacetilasa 2/genética , Lisina Acetiltransferasa 5/genética , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/terapia , Anciano de 80 o más Años , Animales , Drosophila melanogaster , Femenino , Homeostasis/genética , Homeostasis/fisiología , Humanos , Aprendizaje/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Plasticidad Neuronal/genética , Placa Amiloide/genética , Placa Amiloide/prevención & control , Olfato
13.
J Neurochem ; 143(3): 320-333, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28628228

RESUMEN

Schizophrenia (SCZ) is characterized not only by psychosis, but also by working memory and executive functioning deficiencies, processes that rely on the prefrontal cortex (PFC). Because these cognitive impairments emerge prior to psychosis onset, we investigated synaptic function during development in the neurodevelopmental methylazoxymethanol (MAM) model for SCZ. Specifically, we hypothesize that N-methyl-D-aspartate receptor (NMDAR) hypofunction is attributable to reductions in the NR2B subunit through aberrant epigenetic regulation of gene expression, resulting in deficient synaptic physiology and PFC-dependent cognitive dysfunction, a hallmark of SCZ. Using western blot and whole-cell patch-clamp electrophysiology, we found that the levels of synaptic NR2B protein are significantly decreased in juvenile MAM animals, and the function of NMDARs is substantially compromised. Both NMDA-mEPSCs and synaptic NMDA-eEPSCs are significantly reduced in prelimbic PFC (plPFC). This protein loss during the juvenile period is correlated with an aberrant increase in enrichment of the epigenetic transcriptional repressor RE1-silencing transcription factor (REST) and the repressive histone marker H3K27me3 at the Grin2b promoter, as assayed by ChIP-quantitative polymerase chain reaction. Glutamate hypofunction has been a prominent hypothesis in the understanding of SCZ pathology; however, little attention has been given to the NMDAR system in the developing PFC in models for SCZ. Our work is the first to confirm that NMDAR hypofunction is a feature of early postnatal development, with epigenetic hyper-repression of the Grin2b promoter being a contributing factor. The selective loss of NR2B protein and subsequent synaptic dysfunction weakens plPFC function during development and may underlie early cognitive impairments in SCZ models and patients. Read the Editorial Highlight for this article on page 264.


Asunto(s)
Epigénesis Genética/fisiología , Corteza Prefrontal/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Esquizofrenia/patología , Animales , Animales Recién Nacidos , Trastornos del Conocimiento/etiología , Modelos Animales de Enfermedad , Epigénesis Genética/efectos de los fármacos , Agonistas de Aminoácidos Excitadores/farmacología , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Postsinápticos Excitadores/fisiología , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/fisiología , Técnicas In Vitro , Masculino , Acetato de Metilazoximetanol/análogos & derivados , Acetato de Metilazoximetanol/toxicidad , N-Metilaspartato/farmacología , Neuronas/efectos de los fármacos , Neuronas/fisiología , Técnicas de Placa-Clamp , Corteza Prefrontal/citología , Corteza Prefrontal/efectos de los fármacos , Embarazo , Ratas , Receptores de N-Metil-D-Aspartato/genética , Esquizofrenia/inducido químicamente , Esquizofrenia/complicaciones , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/farmacología
14.
PLoS One ; 11(7): e0159623, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27454757

RESUMEN

Environmental enrichment (EE) conditions have beneficial effects for reinstating cognitive ability in neuropathological disorders like Alzheimer's disease (AD). While EE benefits involve epigenetic gene control mechanisms that comprise histone acetylation, the histone acetyltransferases (HATs) involved remain largely unknown. Here, we examine a role for Tip60 HAT action in mediating activity- dependent beneficial neuroadaptations to EE using the Drosophila CNS mushroom body (MB) as a well-characterized cognition model. We show that flies raised under EE conditions display enhanced MB axonal outgrowth, synaptic marker protein production, histone acetylation induction and transcriptional activation of cognition linked genes when compared to their genotypically identical siblings raised under isolated conditions. Further, these beneficial changes are impaired in both Tip60 HAT mutant flies and APP neurodegenerative flies. While EE conditions provide some beneficial neuroadaptive changes in the APP neurodegenerative fly MB, such positive changes are significantly enhanced by increasing MB Tip60 HAT levels. Our results implicate Tip60 as a critical mediator of EE-induced benefits, and provide broad insights into synergistic behavioral and epigenetic based therapeutic approaches for treatment of cognitive disorder.


Asunto(s)
Cognición , Proteínas de Drosophila/genética , Ambiente , Histona Acetiltransferasas/genética , Cuerpos Pedunculados/fisiología , Acetilación , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Biomarcadores , Núcleo Celular/metabolismo , Drosophila , Proteínas de Drosophila/metabolismo , Regulación de la Expresión Génica , Histona Acetiltransferasas/metabolismo , Histonas/metabolismo , Sistemas de Lectura Abierta , Regiones Promotoras Genéticas , Transporte de Proteínas , Células Piramidales/metabolismo , Ratas , Sinapsis/metabolismo , Transcripción Genética
15.
Fly (Austin) ; 9(1): 22-8, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26327426

RESUMEN

Disruption of epigenetic gene control mechanisms involving histone acetylation in the brain causes cognitive impairment, a debilitating hallmark of most neurodegenerative disorders. Histone acetylation regulates cognitive gene expression via chromatin packaging control in neurons. Unfortunately, the histone acetyltransferases (HATs) that generate such neural epigenetic signatures and their mechanisms of action remain unclear. Our recent findings provide insight into this question by demonstrating that Tip60 HAT action is critical for morphology and function of the mushroom body (MB), the learning and memory center in the Drosophila brain. We show that Tip60 is robustly produced in MB Kenyon cells and extending axonal lobes and that targeted MB Tip60 HAT loss results in axonal outgrowth disruption. Functional consequences of loss and gain of Tip60 HAT levels in the MB are evidenced by defects in memory. Tip60 ChIP-Seq analysis reveals enrichment for genes that function in cognitive processes and accordingly, key genes representing these pathways are misregulated in the Tip60 HAT mutant fly brain. Remarkably, increasing levels of Tip60 in the MB rescues learning and memory deficits resulting from Alzheimer's disease associated amyloid precursor protein (APP) induced neurodegeneration. Our studies highlight the potential of HAT activators as a therapeutic option for cognitive disorders.


Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Epigénesis Genética , Histona Acetiltransferasas/metabolismo , Memoria/fisiología , Cuerpos Pedunculados/fisiología , Animales
16.
Mar Pollut Bull ; 100(1): 562-566, 2015 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-26323860

RESUMEN

A baseline investigation into heavy metal status in the mangrove sediments was conducted in Shenzhen, China where rapid urban development has caused severe environmental contamination. It is found that heavy metal contamination in this mangrove wetland is characterized by the dominant presence of tungsten and cobalt, which is markedly different from the neighboring Hong Kong and other parts of the world. The vertical variation pattern of these two metals along the sediment profile differed from other heavy metals, suggesting an increasing influx of tungsten and cobalt into the investigated mangrove habitat, as a result of uncontrolled discharge of industrial wastewater from factories that produce or use chemical compounds or alloys containing these two heavy metals. Laboratory simulation experiment indicated that seawater had a stronger capacity to mobilize sediment-borne tungsten and cobalt, as compared to deionized water, diluted acetic, sulfuric and nitric acids.


Asunto(s)
Cobalto/análisis , Sedimentos Geológicos/análisis , Tungsteno/análisis , Contaminantes Químicos del Agua/análisis , China , Cobalto/química , Ecosistema , Monitoreo del Ambiente/métodos , Sedimentos Geológicos/química , Hong Kong , Metales Pesados/análisis , Agua de Mar/química , Tungsteno/química , Urbanización , Contaminantes Químicos del Agua/química , Humedales
17.
Genetics ; 198(4): 1571-86, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25326235

RESUMEN

Disruption of epigenetic gene control mechanisms in the brain causes significant cognitive impairment that is a debilitating hallmark of most neurodegenerative disorders, including Alzheimer's disease (AD). Histone acetylation is one of the best characterized of these epigenetic mechanisms that is critical for regulating learning- and memory- associated gene expression profiles, yet the specific histone acetyltransferases (HATs) that mediate these effects have yet to be fully characterized. Here, we investigate an epigenetic role for the HAT Tip60 in learning and memory formation using the Drosophila CNS mushroom body (MB) as a well-characterized cognition model. We show that Tip60 is endogenously expressed in the Kenyon cells, the intrinsic neurons of the MB, and in the MB axonal lobes. Targeted loss of Tip60 HAT activity in the MB causes thinner and shorter axonal lobes while increasing Tip60 HAT levels cause no morphological defects. Functional consequences of both loss and gain of Tip60 HAT levels in the MB are evidenced by defects in immediate-recall memory. Our ChIP-Seq analysis reveals that Tip60 target genes are enriched for functions in cognitive processes, and, accordingly, key genes representing these pathways are misregulated in the Tip60 HAT mutant fly brain. Remarkably, we find that both learning and immediate-recall memory deficits that occur under AD-associated, amyloid precursor protein (APP)-induced neurodegenerative conditions can be effectively rescued by increasing Tip60 HAT levels specifically in the MB. Together, our findings uncover an epigenetic transcriptional regulatory role for Tip60 in cognitive function and highlight the potential of HAT activators as a therapeutic option for neurodegenerative disorders.


Asunto(s)
Proteínas de Drosophila/genética , Drosophila/fisiología , Epigénesis Genética , Histona Acetiltransferasas/genética , Aprendizaje , Memoria , Animales , Encéfalo/embriología , Encéfalo/metabolismo , Línea Celular , Modelos Animales de Enfermedad , Proteínas de Drosophila/metabolismo , Activación Enzimática , Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Histona Acetiltransferasas/metabolismo , Cuerpos Pedunculados/embriología , Cuerpos Pedunculados/metabolismo , Enfermedades Neurodegenerativas/inducido químicamente , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/metabolismo , Neuronas/metabolismo
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