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1.
Br J Clin Psychol ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38715445

RESUMEN

BACKGROUND: Post-traumatic stress disorder (PTSD) poses a global public health challenge. Evidence-based psychotherapies (EBPs) for PTSD reduce symptoms and improve functioning (Forbes et al., Guilford Press, 2020, 3). However, a number of barriers to access and engagement with these interventions prevail. As a result, the use of EBPs in community settings remains disappointingly low (Charney et al., Psychological Trauma: Theory, Research, Practice, and Policy, 11, 2019, 793; Richards et al., Community Mental Health Journal, 53, 2017, 215), and not all patients who receive an EBP for PTSD benefit optimally (Asmundson et al., Cognitive Behaviour Therapy, 48, 2019, 1). Advancements in artificial intelligence (AI) have introduced new possibilities for increasinfg access to and quality of mental health interventions. AIMS: The present paper reviews key barriers to accessing and engaging in EBPs for PTSD, discusses current applications of AI in PTSD treatment and provides recommendations for future AI integrations aimed at reducing barriers to access and engagement. DISCUSSION: We propose that AI may be utilized to (1) assess treatment fidelity; (2) elucidate novel predictors of treatment dropout and outcomes; and (3) facilitate patient engagement with the tasks of therapy, including therapy practice. Potential avenues for technological advancements are also considered.

2.
IEEE J Biomed Health Inform ; 27(1): 457-468, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36279347

RESUMEN

Deep learning approaches for medical image analysis are limited by small data set size due to factors such as patient privacy and difficulties in obtaining expert labelling for each image. In medical imaging system development pipelines, phases for system development and classification algorithms often overlap with data collection, creating small disjoint data sets collected at numerous locations with differing protocols. In this setting, merging data from different data collection centers increases the amount of training data. However, a direct combination of datasets will likely fail due to domain shifts between imaging centers. In contrast to previous approaches that focus on a single data set, we add a domain adaptation module to a neural network and train using multiple data sets. Our approach encourages domain invariance between two multispectral autofluorescence imaging (maFLIM) data sets of in vivo oral lesions collected with an imaging system currently in development. The two data sets have differences in the sub-populations imaged and in the calibration procedures used during data collection. We mitigate these differences using a gradient reversal layer and domain classifier. Our final model trained with two data sets substantially increases performance, including a significant increase in specificity. We also achieve a significant increase in average performance over the best baseline model train with two domains (p = 0.0341). Our approach lays the foundation for faster development of computer-aided diagnostic systems and presents a feasible approach for creating a robust classifier that aligns images from multiple data centers in the presence of domain shifts.


Asunto(s)
Neoplasias de la Boca , Redes Neurales de la Computación , Humanos , Algoritmos , Diagnóstico por Imagen
3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 3894-3897, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34892083

RESUMEN

In contrast to previous studies that focused on classical machine learning algorithms and hand-crafted features, we present an end-to-end neural network classification method able to accommodate lesion heterogeneity for improved oral cancer diagnosis using multispectral autofluorescence lifetime imaging (maFLIM) endoscopy. Our method uses an autoencoder framework jointly trained with a classifier designed to handle overfitting problems with reduced databases, which is often the case in healthcare applications. The autoencoder guides the feature extraction process through the reconstruction loss and enables the potential use of unsupervised data for domain adaptation and improved generalization. The classifier ensures the features extracted are task-specific, providing discriminative information for the classification task. The data-driven feature extraction method automatically generates task-specific features directly from fluorescence decays, eliminating the need for iterative signal reconstruction. We validate our proposed neural network method against support vector machine (SVM) baselines, with our method showing a 6.5%-8.3% increase in sensitivity. Our results show that neural networks that implement data-driven feature extraction provide superior results and enable the capacity needed to target specific issues, such as inter-patient variability and the heterogeneity of oral lesions.Clinical relevance- We improve standard classification algorithms for in vivo diagnosis of oral cancer lesions from maFLIm for clinical use in cancer screening, reducing unnecessary biopsies and facilitating early detection of oral cancer.


Asunto(s)
Neoplasias , Redes Neurales de la Computación , Algoritmos , Humanos , Aprendizaje Automático , Máquina de Vectores de Soporte
4.
Cancers (Basel) ; 13(19)2021 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-34638237

RESUMEN

Multispectral autofluorescence lifetime imaging (maFLIM) can be used to clinically image a plurality of metabolic and biochemical autofluorescence biomarkers of oral epithelial dysplasia and cancer. This study tested the hypothesis that maFLIM-derived autofluorescence biomarkers can be used in machine-learning (ML) models to discriminate dysplastic and cancerous from healthy oral tissue. Clinical widefield maFLIM endoscopy imaging of cancerous and dysplastic oral lesions was performed at two clinical centers. Endoscopic maFLIM images from 34 patients acquired at one of the clinical centers were used to optimize ML models for automated discrimination of dysplastic and cancerous from healthy oral tissue. A computer-aided detection system was developed and applied to a set of endoscopic maFLIM images from 23 patients acquired at the other clinical center, and its performance was quantified in terms of the area under the receiver operating characteristic curve (ROC-AUC). Discrimination of dysplastic and cancerous from healthy oral tissue was achieved with an ROC-AUC of 0.81. This study demonstrates the capabilities of widefield maFLIM endoscopy to clinically image autofluorescence biomarkers that can be used in ML models to discriminate dysplastic and cancerous from healthy oral tissue. Widefield maFLIM endoscopy thus holds potential for automated in situ detection of oral dysplasia and cancer.

5.
J Psychiatr Res ; 137: 613-620, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33190842

RESUMEN

Social impairment is a cardinal feature of schizophrenia spectrum disorders (SZ). Smaller social network size, diminished social skills, and loneliness are highly prevalent. Existing, gold-standard assessments of social impairment in SZ often rely on self-reported information that depends on retrospective recall and detailed accounts of complex social behaviors. This is particularly problematic in people with SZ given characteristic cognitive impairments and reduced insight. Ecological Momentary Assessment (EMA; repeated self-reports completed in the context of daily life) allows for the measurement of social behavior as it occurs in vivo, yet still relies on participant input. Momentary characterization of behavior using smartphone sensors (e.g., GPS, microphone) may also provide ecologically valid indicators of social functioning. In the current study we tested associations between both active (e.g., EMA-reported number of interactions) and passive (GPS-based mobility, conversations captured by microphone) smartphone-based measures of social activity and measures of social functioning and loneliness to examine the promise of such measures for understanding social impairment in SZ. Our results indicate that passive markers of mobility were more consistently associated with EMA measures of social behavior in controls than in people with SZ. Furthermore, dispositional loneliness showed associations with mobility metrics in both groups, while general social functioning was less related to these metrics. Finally, interactions detected in the ambient audio were more tied to social functioning in SZ than in controls. Findings speak to the promise of smartphone-based digital phenotyping as an approach to understanding objective markers of social activity in people with and without schizophrenia.


Asunto(s)
Esquizofrenia , Teléfono Inteligente , Evaluación Ecológica Momentánea , Humanos , Estudios Retrospectivos , Interacción Social
6.
Clin Proteomics ; 17: 12, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32265614

RESUMEN

BACKGROUND: Sialolithiasis or salivary gland stones are associated with high clinical morbidity. The advances in the treatment of sialolithiasis has been limited, however, by our understanding of their composition. More specifically, there is little information regarding the formation and composition of the protein matrix, the role of mineralogical deposition, or the contributions of cell epithelium and secretions from the salivary glands. A better understanding of these stone characteristics could pave the way for future non-invasive treatment strategies. METHODS: Twenty-nine high-quality ductal stone samples were analyzed. The preparation included successive washings to avoid contamination from saliva and blood. The sialoliths were macerated in liquid nitrogen and the maceration was subjected to a sequential, four-step, protein extraction. The four fractions were pooled together, and a standardized aliquot was subjected to tandem liquid chromatography mass spectrometry (LCMS). The data output was subjected to a basic descriptive statistical analysis for parametric confirmation and a subsequent G.O.-KEGG data base functional analysis and classification for biological interpretation. RESULTS: The LC-MS output detected 6934 proteins, 824 of which were unique for individual stones. An example of our sialolith protein data is available via ProteomeXchange with the identifier PXD012422. More important, the sialoliths averaged 53% homology with bone-forming proteins that served as a standard comparison, which favorably compared with 62% homology identified among all sialolith sample proteins. The non-homologous protein fraction had a highly variable protein identity. The G.O.-KEGG functional analysis indicated that extracellular exosomes are a primary cellular component in sialolithiasis. Light and electron microscopy also confirmed the presence of exosomal-like features and the presence of intracellular microcrystals. CONCLUSION: Sialolith formation presents similarities with the hyperoxaluria that forms kidney stones, which suggests the possibility of a common origin. Further verification of a common origin could fundamentally change the way in which lithiasis is studied and treated.

7.
Environ Sci Pollut Res Int ; 27(2): 1417-1427, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31749002

RESUMEN

The differences in the mechanism of cadmium (Cd) accumulation in the grains of different wheat (Triticum aestivum L.) cultivars remain unclear. Thus, we conducted a hydroponic experiment in a greenhouse to compare root surface adsorption, root uptake, subcellular distribution, and chemical forms of Cd between low- and high-Cd-accumulating wheat cultivars at seedling stage, to improve our understanding of the differences between cultivars. The results showed that Cd adsorbed on the root surface was mainly in a complexed form, and the total amount of Cd on the Yaomai16 (YM, high-Cd-accumulating genotypes) root surface was higher (p < 0.05) than that on Xinmai9817 (XM, low-Cd-accumulating genotypes). A large amount of Cd ions adsorbed on root surface would cause plant damage and inhibit growth. Comparing the root-to-shoot translocation factors of Cd, the transfer coefficients of YM were 1.017, 1.446, 1.464, and 1.030 times higher than those of XM under 5, 10, 50, and 100 µmol L-1 Cd treatments, respectively. The subcellular distribution of Cd under Cd exposure is mainly in the cell wall and soluble fraction. The proportions of Cd in YM shoot soluble fraction were higher than those in XM, which was the main detoxification mechanism limiting the activity of Cd and may be responsible for low Cd accumulation in grains, while the effects of the chemical forms of Cd on migration and detoxification were not found to be related to Cd accumulation in the kernels.


Asunto(s)
Cadmio/análisis , Raíces de Plantas/metabolismo , Contaminantes del Suelo/análisis , Triticum/metabolismo , Adsorción , Hidroponía , Raíces de Plantas/química , Semillas/metabolismo , Fracciones Subcelulares/química
8.
Oncotarget ; 8(29): 47076-47089, 2017 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-28423364

RESUMEN

Helicobacter pylori infection triggers a cascade of inflammatory stages that may lead to the appearance of non-atrophic gastritis, multifocal atrophic, intestinal metaplasia, dysplasia, and cancer. Deleted in malignant brain tumors 1 (DMBT1) belongs to the group of secreted scavenger receptor cysteine-rich proteins and is considered to be involved in host defense by binding to pathogens. Initial studies showed its deletion and loss of expression in a variety of tumors but the role of this gene in tumor development is not completely understood. Here, we examined the role of DMBT1 in gastric precancerous lesions in Caucasian, African American and Hispanic individuals as well as in the development of gastric pathology in a mouse model of H. pylori infection. We found that in 3 different populations, mucosal DMBT1 expression was significantly increased (2.5 fold) in individuals with dysplasia compared to multifocal atrophic gastritis without intestinal metaplasia; the increase was also observed in individuals with advanced gastritis and positive H. pylori infection. In our animal model, H. pylori infection of Dmbt1-/- mice resulted in significantly higher levels of gastritis, more extensive mucous metaplasia and reduced Il33 expression levels in the gastric mucosa compared to H. pylori-infected wild type mice. Our data in the animal model suggest that in response to H. pylori infection DMBT1 may mediate mucosal protection reducing the risk of developing gastric precancerous lesions. However, the increased expression in human gastric precancerous lesions points to a more complex role of DMBT1 in gastric carcinogenesis.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Lesiones Precancerosas/genética , Receptores de Superficie Celular/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Animales , Proteínas de Unión al Calcio , Proteínas de Unión al ADN , Modelos Animales de Enfermedad , Etnicidad/genética , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Perfilación de la Expresión Génica , Estudios de Asociación Genética , Infecciones por Helicobacter/complicaciones , Humanos , Ratones , Ratones Noqueados , Estadificación de Neoplasias , Proteínas Supresoras de Tumor
9.
Rev. argent. microbiol ; 49(1): 55-61, mar. 2017. tab
Artículo en Inglés | LILACS | ID: biblio-843183

RESUMEN

The microbiological quality of honey obtained from different processing points and the environmental quality within honey houses were assessed in the Pampas Region (Argentina). Mold and yeast (MY), culturable heterotrophic mesophilic bacteria (CHMB), the number of spore-forming bacteria as well as the presence of Shigella spp., Salmonella spp. and fecal coliforms were evaluated in 163 samples. These samples were taken from eight honey houses. Results showed that 89 samples had ≤10 CFU of MY/g honey, 69 ranged from 10 to 50 CFU/g and two reached 65.5 CFU/g. Eighty one percent of the samples showed ≤30 CFU of CHMB/g honey and only seven samples had between 50 and 54.25 CFU/g. Thirty six honey samples were obtained from drums: in 25 samples (69.4%) CHMB counts were less than ≤30 CFU/g of honey; in 20 samples (55.5%) the values of MY were between 10 and 50 CFU/g honey and total coliforms were only detected in 20 samples. Fecal coliforms, spores of clostridia as well as Salmonella spp. and Shigella spp were not detected and less than 50 spores of Bacillus spp. per g were observed in the honey from drums. Therefore, the microbiological honey quality within the honey houses did not show any sanitary risks. Our results were reported to honey house owners to help them understand the need to reinforce proper honey handling and sanitation practices.


Este estudio evaluó la calidad microbiológica de la miel dentro de varias plantas de extracción de miel y la calidad del medio ambiente de las mismas en la Región Pampeana (Argentina). Se trabajó con 163 muestras de miel provenientes de 8 plantas de extracción. Se cuantificaron hongos y levaduras, bacterias aeróbicas mesófilas, bacterias esporuladas y esporas de clostridios. Asimismo, se determinó la presencia de Salmonella spp., Shigella spp. y coliformes fecales. Los resultados mostraron que por g de miel, 89 muestras tuvieron menos de 10 UFC de hongos y levaduras, 69 tuvieron entre 10 y 50 UFC y 2 alcanzaron 65,5 UFC. Ochenta y uno por ciento de las muestras presentaron menos de 30 UFC de bacterias aeróbicas mesófilas por g de miel mientras que solo 7 tuvieron entre 50 y 54,25 UFC. Se obtuvieron 36 muestras de miel directamente de tambor: los conteos de bacterias aeróbicas mesófilas fueron ≤ 30 UFC/g de miel en 25 muestras (69,4%); los valores de hongos y levaduras estuvieron entre 10 y 50 UFC en 20 muestras (55,5%) y solo se detectaron coliformes totales. No se observaron coliformes fecales, esporas de clostridios así como tampoco Salmonella spp. y Shigella spp. y se obtuvieron menos de 50 esporas de Bacillus spp./g en miel de los tambores. Se concluye que la calidad microbiológica de la miel en las plantas de extracción no presentó riesgo sanitario. Los resultados fueron entregados a los dueños de las mismas como aporte para que valoren la importancia de reforzar la aplicación de buenas prácticas de manejo y saneamiento.


Asunto(s)
Bacillus , Hongos , Miel , Argentina , Bacillus/aislamiento & purificación , Bacterias , Microbiología de Alimentos , Hongos/aislamiento & purificación , Miel/microbiología
10.
Rev Argent Microbiol ; 49(1): 55-61, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27989610

RESUMEN

The microbiological quality of honey obtained from different processing points and the environmental quality within honey houses were assessed in the Pampas Region (Argentina). Mold and yeast (MY), culturable heterotrophic mesophilic bacteria (CHMB), the number of spore-forming bacteria as well as the presence of Shigella spp., Salmonella spp. and fecal coliforms were evaluated in 163 samples. These samples were taken from eight honey houses. Results showed that 89 samples had ≤10CFU of MY/g honey, 69 ranged from 10 to 50CFU/g and two reached 65.5CFU/g. Eighty one percent of the samples showed ≤30CFU of CHMB/g honey and only seven samples had between 50 and 54.25CFU/g. Thirty six honey samples were obtained from drums: in 25 samples (69.4%) CHMB counts were less than ≤30CFU/g of honey; in 20 samples (55.5%) the values of MY were between 10 and 50CFU/g honey and total coliforms were only detected in 20 samples. Fecal coliforms, spores of clostridia as well as Salmonella spp. and Shigella spp were not detected and less than 50 spores of Bacillus spp. per g were observed in the honey from drums. Therefore, the microbiological honey quality within the honey houses did not show any sanitary risks. Our results were reported to honey house owners to help them understand the need to reinforce proper honey handling and sanitation practices.


Asunto(s)
Bacillus , Hongos , Miel , Argentina , Bacillus/aislamiento & purificación , Bacterias , Microbiología de Alimentos , Hongos/aislamiento & purificación , Miel/microbiología
11.
Otolaryngol Clin North Am ; 49(2): 381-93, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26912292

RESUMEN

Nonneoplastic disorders of the salivary glands involve inflammatory processes. These disorders have been managed conservatively with antibiotics, warm compresses, massage, sialogogues, and adequate hydration. Up to 40% of patients may have an inadequate response or persistent symptoms. When conservative techniques fail, the next step is operative intervention. Sialendoscopy offers a minimally invasive option for the diagnosis and management of chronic inflammatory disorders of the salivary glands and offers the option of gland and function preservation. In this article, we review some of the more common nonneoplastic disorders of the parotid gland, indications for diagnostic and interventional sialendoscopy, and operative techniques.


Asunto(s)
Endoscopía/métodos , Glándula Parótida/diagnóstico por imagen , Parotiditis/diagnóstico por imagen , Cálculos de las Glándulas Salivales/diagnóstico por imagen , Enfermedad Aguda , Enfermedad Crónica , Humanos , Cálculos de las Glándulas Salivales/cirugía , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
12.
Rev. Soc. Argent. Diabetes ; 49(2): 50-68, 2015.
Artículo en Español | LILACS | ID: lil-774212

RESUMEN

Introducción: la hipertensión arterial (HA) y la diabetes mellitus (DM) son enfermedades crónicas de alta prevalencia que se encuentran frecuentemente asociadas. Objetivos: brindar los conocimientos para la práctica clínica que favorezcan la toma de decisiones diagnósticas y terapéuticas adecuadas, basadas en las evidencias científicas actuales. Materiales y métodos: utilizando la evidencia disponible, los grandes ensayos clínicos publicados en los últimos cuatro años y la adaptación de los recursos diagnósticos y terapéuticos de nuestro país se elaboraron las presentes “Recomendaciones para la Práctica Clínica”. Conclusiones: la HA aumenta la progresión y el desarrollo de las complicaciones crónicas micro y macrovasculares de la DM. El impacto del tratamiento de la HA es significativo en la reducción de la morbimortalidad de las personas con DM. Por ello, el tratamiento debe ser temprano y las metas de objetivo terapéutico deberán ser individualizadas según grupo etario, comorbilidades y daño de órgano blanco. En todas las personas con HA, tengan o no DM y/o enfermedad renal crónica (ERC), el objetivo es alcanzar una PA <140/90 mmHg. Podrán considerarse objetivos más cercanos a 130/80 mmHg en jóvenes, sin comorbilidades, con larga expectativa de vida y menor tiempo de diagnóstico de DM: en quienes tendrían beneficios a nivel renal o en quienes el riesgo de ACV es sustancial, si se logran sin efectos adversos asociados al tratamiento. Los IECA o ARA II son los fármacos de primera elección excepto en casos de intolerancia o contraindicación. Un bajo porcentaje de personas logra el objetivo terapéutico. La educación es una herramienta fundamental para mejorar la adherencia al tratamiento.


Asunto(s)
Diabetes Mellitus , Hipertensión , Terapéutica
13.
Nucleic Acids Res ; 39(18): 8017-28, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21727086

RESUMEN

Apurinic/apyrimidinic endonuclease-1 (APE1) is a multifunctional DNA repair/gene regulatory protein in mammalian cells, and was recently reported to be phosphorylated at Thr233 by CDK5. We here report that ubiquitination of T233E APE1, a mimicry of phospho-T233 APE1, was markedly increased in multiple cell lines. Expression of CDK5 enhanced monoubiquitination of endogenous APE1. Polyubiquitinated APE1 was decreased when K48R ubiquitin was expressed, suggesting that polyubiquitination was mediated mainly through Lys48 of ubiquitin. The ubiquitination activity of MDM2, consistent in its role for APE1 ubiquitination, was increased for T233E APE1 compared to the wild-type APE1. In mouse embryonic fibroblasts lacking the MDM2 gene, ubiquitination of T233E APE1 was still observed probably because of the decreased degradation activity for monoubiquitinated APE1 and because of backup E3 ligases in the cells. Monoubiquitinated APE1 was present in the nucleus, and analyzing global gene expression profiles with or without induction of a ubiquitin-APE1 fusion gene suggested that monoubiquitination enhanced the gene suppression activity of APE1. These data reveal a delicate balance of ubiquitination and phosphorylation activities that alter the gene regulatory function of APE1.


Asunto(s)
Quinasa 5 Dependiente de la Ciclina/metabolismo , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Ubiquitinación , Sustitución de Aminoácidos , Animales , Línea Celular , Línea Celular Tumoral , ADN-(Sitio Apurínico o Apirimidínico) Liasa/química , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , Ácido Glutámico/genética , Humanos , Lisina/metabolismo , Ratones , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Treonina/genética
14.
Theor Appl Genet ; 123(3): 369-82, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21505831

RESUMEN

Quantitative trait loci (QTLs) for frost and drought tolerance, and winter survival in the field, were mapped in meadow fescue (Festuca pratensis Huds.) and compared with corresponding traits in Triticeae and rice to study co-location with putatively orthologous QTLs and known abiotic stress tolerance genes. The genomes of grass species are highly macrosyntenic; however, the Festuca/Lolium and Triticeae homoeologous chromosomes 4 and 5 show major structural differences that is especially interesting in comparative genomics of frost tolerance. The locations of two frost tolerance/winter survival QTLs on Festuca chromosome 5F correspond most likely to the Fr-A1 and Fr-A2 loci on wheat homoeologous group 5A chromosomes. A QTL for long-term drought tolerance on chromosome 3F (syntenic with rice 1) support evidence from introgression of Festuca genome segments onto homoeologous Lolium chromosomes (3L) that this genome region is an excellent source of tolerance towards drought stress. The coincident location of several stress tolerance QTL in Festuca with QTL and genes in Triticeae species, notably dehydrins, CBF transcription factors and vernalisation response genes indicate the action of structural or regulatory genes conserved across evolutionarily distant species.


Asunto(s)
Mapeo Cromosómico , Frío , Sequías , Festuca/genética , Sitios de Carácter Cuantitativo , Cromosomas de las Plantas , Clonación Molecular , Evolución Molecular , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Lolium/genética , Oryza/genética , Estaciones del Año , Factores de Transcripción/genética , Triticum/genética
15.
Cell Mol Life Sci ; 67(21): 3609-20, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20711647

RESUMEN

A key issue in studying mammalian DNA base excision repair is how its component proteins respond to a plethora of cell-signaling mediators invoked by DNA damage and stress-inducing agents such as reactive oxygen species, and how the actions of individual BER proteins are attributed to cell survival or apoptotic/necrotic death. This article reviews the past and recent progress on posttranslational modification (PTM) of mammalian apurinic/apyrimidinic (AP) endonuclease 1 (APE1).


Asunto(s)
ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Procesamiento Proteico-Postraduccional , Acetilación , Animales , ADN-(Sitio Apurínico o Apirimidínico) Liasa/química , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , Humanos , Modelos Moleculares , Fosforilación , Ubiquitinación
16.
Nucleic Acids Res ; 36(5): 1555-66, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18208837

RESUMEN

The human AP-endonuclease (APE1/Ref-1), an essential multifunctional protein, plays a central role in the repair of oxidative base damage via the DNA base excision repair (BER) pathway. The mammalian AP-endonuclease (APE1) overexpression is often observed in tumor cells, and confers resistance to various anticancer drugs; its downregulation sensitizes tumor cells to those agents via induction of apoptosis. Here we show that wild type (WT) but not mutant p53 negatively regulates APE1 expression. Time-dependent decrease was observed in APE1 mRNA and protein levels in the human colorectal cancer line HCT116 p53(+/+), but not in the isogenic p53 null mutant after treatment with camptothecin, a DNA topoisomerase I inhibitor. Furthermore, ectopic expression of WTp53 in the p53 null cells significantly reduced both endogenous APE1 and APE1 promoter-dependent luciferase expression in a dose-dependent fashion. Chromatin immunoprecipitation assays revealed that endogenous p53 is bound to the APE1 promoter region that includes a Sp1 site. We show here that WTp53 interferes with Sp1 binding to the APE1 promoter, which provides a mechanism for the downregulation of APE1. Taken together, our results demonstrate that WTp53 is a negative regulator of APE1 expression, so that repression of APE1 by p53 could provide an additional pathway for p53-dependent induction of apoptosis in response to DNA damage.


Asunto(s)
Daño del ADN , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , Regulación hacia Abajo , Regulación Enzimológica de la Expresión Génica , Proteína p53 Supresora de Tumor/metabolismo , Línea Celular Tumoral , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Humanos , Mutación , Regiones Promotoras Genéticas , ARN Mensajero/metabolismo , Elementos de Respuesta , Factor de Transcripción Sp1/metabolismo , Proteína p53 Supresora de Tumor/genética
17.
Biocell ; 29(3): 279-285, Aug.-Dec. 2005. graf, tab
Artículo en Inglés | LILACS | ID: lil-633234

RESUMEN

Seed size is a crucial plant trait that may potentially affect not only immediate seedling success but also the subsequent generation. We examined variation in seed weight of Wyoming sagebrush (Artemisia tridentata ssp. wyomingensis Beetle and Young), an excellent candidate species for rangeland restoration. The working hypothesis was that a major fraction of spatial and temporal variability in seed size (weight) of Wyoming sagebrush could be explained by variations in mean monthly temperatures and precipitation. Seed collection was conducted at Battle Mountain and Eden Valley sites in northern Nevada, USA, during November of 2002 and 2003. Frequency distributions of seed weight varied from leptokurtic to platykurtic, and from symmetry to skewness to the right for both sites and years. Mean seed weight varied by a factor of 1.4 between locations and years. Mean seed weight was greater (P<0.05) in 2003 than in 2002 at both sites. This can partially be attributed to 55% greater precipitation in 2003 than 2002, since mean monthly temperatures were similar (P>0.05) in all study situations. Simple linear regression showed that monthly precipitation (March to November) explained 85% of the total variation in mean seed weight ( P=0.079). Since the relationship between mean monthly temperature (June-November) and mean seed weight was not significant (r²=0.00, P=0.431), this emphasizes the importance of precipitation as an important determinant of mean seed weight. Our results suggest that the precipitation regime to which the mother plant is exposed can have a significant effect on sizes of seeds produced. Hence, seasonal changes in water availability would tend to alter size distributions of produced offspring.


Asunto(s)
Artemisia/fisiología , Variación Genética , Semillas/crecimiento & desarrollo , Semillas/fisiología , Clima , Modelos Lineales , Nevada , Lluvia , Estaciones del Año , Especificidad de la Especie , Temperatura
18.
Interciencia ; 30(10): 631-637, oct. 2005. tab, graf
Artículo en Inglés | LILACS | ID: lil-430643

RESUMEN

El tamaño de la semilla y las características de la germinación afectan el desempeño de las plántulas en estadios tempranos. El objetivo de este estudio fue investigar las relaciones entre tamaño de semilla y porcentaje de germinación, tasa de germinación, variación de la germinación con el tiempo y viabilidad de las semillas en artemisa (Artemisia tridentata ssp. wyomingensis Beetle y Young). Las hipótesis de trabajo fueron: 1) para semillas individuales, las tasas y porcentajes de germinación están positivamente relacionados al peso de las semillas; y 2) algunas semillas no teñidas con el TTC no están muertas sino durmientes. Las semillas fueron recolectadas en Battle Mountain y Eden Valley, al norte de Nevada, EEUU, en noviembre 2002 y 2003. Las semillas individuales fueron clasificadas por peso en clases de 0,05mgúsemilla-1, variando de £0,15 a >0,40mgúsemilla-1, y fueron incubadas en oscuridad a 15ºC; las plántulas con radículas ³1,0mm se removieron diariamente durante los primeros 10 días, y luego cada 2 días hasta el día 32. El estudio concluyó el día 37. La prueba del cloruro de trifenil tetrazolio (TTC) se usó para determinar la viabilidad de las semillas no germinadas, y el azul de Evans para separar semillas no germinadas en durmientes o muertas. Los resultados apoyaron ambas hipótesis. La germinación máxima en ambos sitios, años y todos los rangos de semillas se alcanzó 5-6 días luego de la imbibición. Esto sugiere que un suelo húmedo por varios días consecutivos ayudaría a proveer una germinación óptima en campo. El uso del azul de Evans demostró que aunque en pequeño porcentaje (< 5 por ceinto), algunas semillas no teñidas por TTC no estaban muertas sino durmientes, con potencial para germinar dadas condiciones apropiadas. Cuando este arbusto es usado para restaurar pastizales degradados se deberían usar semillas relativamente pesadas, que tienen el mayor potencial para germinar


Asunto(s)
Artemisia , Germinación , Semillas , Agricultura , Estados Unidos
19.
Biocell ; 29(3): 279-85, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16524249

RESUMEN

Seed size is a crucial plant trait that may potentially affect not only immediate seedling success but also the subsequent generation. We examined variation in seed weight of Wyoming sagebrush (Artemisia tridentata ssp. wyomingensis Beetle and Young), an excellent candidate species for rangeland restoration. The working hypothesis was that a major fraction of spatial and temporal variability in seed size (weight) of Wyoming sagebrush could be explained by variations in mean monthly temperatures and precipitation. Seed collection was conducted at Battle Mountain and Eden Valley sites in northern Nevada, USA, during November of 2002 and 2003. Frequency distributions of seed weight varied from leptokurtic to platykurtic, and from symmetry to skewness to the right for both sites and years. Mean seed weight varied by a factor of 1.4 between locations and years. Mean seed weight was greater (P < 0.05) in 2003 than in 2002 at both sites. This can partially be attributed to 55% greater precipitation in 2003 than 2002, since mean monthly temperatures were similar (P > 0.05) in all study situations. Simple linear regression showed that monthly precipitation (March to November) explained 85% of the total variation in mean seed weight (P = 0.079). Since the relationship between mean monthly temperature (June-November) and mean seed weight was not significant (r2 = 0.00, P = 0.431), this emphasizes the importance of precipitation as an important determinant of mean seed weight. Our results suggest that the precipitation regime to which the mother plant is exposed can have a significant effect on sizes of seeds produced. Hence, seasonal changes in water availability would tend to alter size distributions of produced offspring.


Asunto(s)
Artemisia/fisiología , Variación Genética , Semillas/crecimiento & desarrollo , Semillas/fisiología , Clima , Modelos Lineales , Nevada , Lluvia , Estaciones del Año , Especificidad de la Especie , Temperatura
20.
Biocell ; 29(3): 279-85, 2005 Dec.
Artículo en Inglés | BINACIS | ID: bin-38234

RESUMEN

Seed size is a crucial plant trait that may potentially affect not only immediate seedling success but also the subsequent generation. We examined variation in seed weight of Wyoming sagebrush (Artemisia tridentata ssp. wyomingensis Beetle and Young), an excellent candidate species for rangeland restoration. The working hypothesis was that a major fraction of spatial and temporal variability in seed size (weight) of Wyoming sagebrush could be explained by variations in mean monthly temperatures and precipitation. Seed collection was conducted at Battle Mountain and Eden Valley sites in northern Nevada, USA, during November of 2002 and 2003. Frequency distributions of seed weight varied from leptokurtic to platykurtic, and from symmetry to skewness to the right for both sites and years. Mean seed weight varied by a factor of 1.4 between locations and years. Mean seed weight was greater (P < 0.05) in 2003 than in 2002 at both sites. This can partially be attributed to 55


greater precipitation in 2003 than 2002, since mean monthly temperatures were similar (P > 0.05) in all study situations. Simple linear regression showed that monthly precipitation (March to November) explained 85


of the total variation in mean seed weight (P = 0.079). Since the relationship between mean monthly temperature (June-November) and mean seed weight was not significant (r2 = 0.00, P = 0.431), this emphasizes the importance of precipitation as an important determinant of mean seed weight. Our results suggest that the precipitation regime to which the mother plant is exposed can have a significant effect on sizes of seeds produced. Hence, seasonal changes in water availability would tend to alter size distributions of produced offspring.

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