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1.
Plant Dis ; 108(8): 2376-2388, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38386299

RESUMEN

Burkholderia glumae causes bacterial leaf blight in rice, and its global spread has been exacerbated by climate change. To understand the genetic diversity and virulence of B. glumae strains isolated from rice cultivars in Perú, 47 isolates were obtained from infected rice fields, all belonging to B. glumae, and confirmed by recA and toxB sequences. The BOX-PCR typing group has 38 genomic profiles, and these turn into seven variable number tandem repeats (VNTR) haplotypes. There was no correlation between clustering and geographical origin. Nineteen strains were selected for phenotypic characterization and virulence, using both the maceration level of the onion bulb proxy and inoculation of seeds of two rice cultivars. Several strains produced pigments other than toxoflavin, which correlated with onion bulb maceration. In terms of virulence at the seed level, all strains produced inhibition at the root and coleoptile level, but the severity of symptoms varied significantly between strains, revealing significant differences in pathogenicity. There is no correlation between maceration and virulence scores, probably reflecting different virulence mechanisms depending on the host infection stage. This is the first study to evaluate the VNTR diversity and virulence of Peruvian strains of B. glumae in two commercial cultivars.


Asunto(s)
Burkholderia , Variación Genética , Oryza , Enfermedades de las Plantas , Oryza/microbiología , Burkholderia/genética , Burkholderia/patogenicidad , Burkholderia/aislamiento & purificación , Enfermedades de las Plantas/microbiología , Virulencia/genética , Filogenia , Repeticiones de Minisatélite
2.
J Undergrad Neurosci Educ ; 22(3): A185-A196, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39355667

RESUMEN

Game-based learning is a promising approach that can promote engagement and deep learning of course content in a fun setting. This article describes the development, implementation, and evaluation of a card game designed to help students develop greater familiarity and comfort with complex neuroscience vocabulary. To play Forbidden Neurds, students within a team take turns acting as the Lead Neurd, who must get the team to guess a Neuroscience word without using any of the Forbidden words listed on the card. The game is designed to help students develop a deeper understanding of neuroscience terminology, identify relationships between terms, identify gaps in their understanding, and reinforce learning. The game was evaluated in a 200-level fundamentals of neuroscience course at a small public liberal arts university. Students showed increased content knowledge through pre-post testing, and a post-game self-reported survey showed that playing Forbidden Neurds enabled students to assess, increase, and apply content knowledge. Gameplay also helped students develop greater communication, critical thinking, and teamwork skills. In addition, students reported experiencing greater engagement through this fun learning activity. This game could act as an adaptable and effective learning tool across a range of neuroscience courses.

3.
J Oncol Pharm Pract ; 28(1): 175-184, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34590525

RESUMEN

OBJECTIVE: Rearranged during transfection genes are present in 1-2% of patients who have non-small cell lung cancer and 10-30% of patients with papillary thyroid cancer. The objective of this article is to review the current rearranged during transfection inhibitors indicated for patients with rearranged during transfection-mutated cancers and their future directions.Data sources: The pivotal phase I/II studies for selpercatinib and pralsetinib were evaluated. Current studies on rearranged during transfection inhibitors were searched on ClinicalTrials.gov using the key word "RET."Data summary: Selpercatinib and pralsetinib were the first two U.S. Food and Drug Administration-approved rearranged during transfection-selective inhibitors for advanced or metastatic rearranged during transfection fusion-positive non-small cell lung cancer, rearranged during transfection-mutant medullary thyroid cancer, and rearranged during transfection fusion-positive thyroid cancer. Both agents showed promising efficacy with objective response rate ranging from 60% to 73% in all aforementioned rearranged during transfection-mutated cancers. Additionally, benefits were seen even in patients with intracranial metastasis at baseline. Both showed favorable safety profiles. Some common class adverse events included elevated liver function tests and hypertension. Hematologic side effects such as anemia and neutropenia were more common with pralsetinib. Selpercatinib had interactions with acid suppressive therapy and specific instructions when used concomitantly. CONCLUSIONS: While the rearranged during transfection inhibitors are generally well-tolerated, each agent possesses slightly different efficacy, side-effect profile, and drug-drug interactions.


Asunto(s)
Carcinoma Neuroendocrino , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogénicas c-ret/genética , Transfección
4.
J Undergrad Neurosci Educ ; 20(2): A120-A145, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-38323063

RESUMEN

Effective science communication has been identified as one of the core competencies of neuroscience education as articulated at the 2017 FUN Workshop. Yet most undergraduate students do not receive explicit instruction on how to effectively communicate science to a diversity of audiences. Instead, communication assignments typically help students become proficient at sharing scientific information with other scientists through research articles, poster presentations or oral presentations. This presents a missed opportunity to instruct students on the complexities of communicating to the general public, the importance of which has come into sharp focus during the COVID-19 pandemic. Translating research findings so they can be understood by a non-specialist audience requires practice and deep learning and can act as a powerful teaching tool to help students build science literacy skills. Here I share the blueprint to a broadly-oriented science communication assignment built to address the core competencies of neuroscience education. The assignment acts as the final project for a 400-level neuropharmacology course at a small public liberal arts university. Students work in small groups to identify a topic of interest and research, script, and record an audio podcast geared towards a general audience. The assignment is scaffolded to allow students to work towards the final submission in small steps and to receive feedback from the instructor and their peers. These feedback steps pair with opportunities to revise their work to further develop students' communication skills. Initial feedback from students suggests the assignment promoted deeper learning and higher engagement with course content.

5.
J Esthet Restor Dent ; 33(4): 636-647, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33665948

RESUMEN

OBJECTIVES: To study the effect of artificial aging on color stability, translucency, and surface roughness of stained all-ceramic restorations. MATERIALS AND METHODS: Disc-shaped specimens were fabricated from six different all-ceramic materials: two glass ceramics (Vita Mark II and Empress CAD), two lithium disilicate based ceramics (e.max and Suprinity), and two zirconia-based materials (ZirCAD LT and ZirCAD MT Multi). The discs were stained using two universal stains; IPS Ivocolor stain or Vita Akzent stain. Color change (ΔE) and the translucency parameter (TP) were measured before and after artificial aging. The surface roughness (Ra) was evaluated using atomic force microscopy, while the surface microstructure was evaluated using scanning electron microscopy (SEM). Quantitative elemental analysis was performed using the energy dispersive X-ray (EDX). Leached ions were analyzed by inductively coupled plasma (ICP) (n = 12, α = 0.05). RESULTS: Artificial aging had significantly changed the color (ΔE) and decreased the translucency (TP) of all stained ceramics. The mean surface roughness (Ra) was significantly increased in all specimens, which was also confirmed in the SEM scans. EDX analysis revealed a decrease in the elemental composition of the stained surface as a result of ceramic degradation, except for Ca and Zn in IPS Ivocolor stain. Furthermore, the ICP analysis revealed that most compositional elements of stain and glaze were detected in the aging solution. CONCLUSIONS: Chemical aging had significantly affected the optical parameters and surface texture of stained monolithic ceramics. CLINICAL SIGNIFICANCE: Stained ceramics are liable to color degradation. Each type of stain should be used with its corresponding type of ceramic. Stained all-ceramic restorations are liable to color change and surface degradation during function.


Asunto(s)
Cerámica , Porcelana Dental , Color , Diseño Asistido por Computadora , Ensayo de Materiales , Propiedades de Superficie
6.
J Undergrad Neurosci Educ ; 20(1): A18-A27, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35540950

RESUMEN

Game-based learning offers a fun and engaging pedagogical approach that can promote greater understanding of course content. This article describes the development, use, and evaluation of a board game designed to test students' understanding of core concepts covered in introductory neuroscience courses-action potentials and synaptic transmission. During the game, students work collaboratively in small teams to build a working synaptic connection by drawing cards featuring proteins and molecules involved in neurotransmission and placing the cards onto specific locations on the pre- and post-synaptic neurons illustrated on the game board. The game requires students to synthesize information learned across different modules to determine what structures are vital to a functioning synapse. In a post-game survey, students reported that playing Signal enabled them to assess, increase, and apply content-specific knowledge, and promoted transferable skills including effective communication and critical thinking. Students also rated the game as an enjoyable learning experience. This board game could serve as an effective and engaging tool to review the fundamentals of neurotransmission across a range of neuroscience and biology courses.

7.
BMC Cardiovasc Disord ; 15: 12, 2015 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-25887230

RESUMEN

BACKGROUND: Heart failure (HF) is one of the most debilitating chronic illnesses. The prevalence is expected to increase due to aging population. The current study aimed to examine the management of heart failure with preserved ejection fraction (HFpEF) including drug use pattern, direct medical cost and humanistic outcome in a local public hospital in Hong Kong. METHODS: The current study adopted the retrospective observational study design. Subjects were recruited from the Heart Failure Registry of the Prince of Wales Hospital in Hong Kong between 2006 and 2008 and completed the Minnesota Living with Heart Failure Questionnaire (MLHFQ) at 3 designated time-points conferred eligibility. Patients with significant valvular disorder were excluded. Each patient's medical record was reviewed for 12 months after the date of admission. Heart failure related admissions, clinic visits, cardiovascular drugs, laboratory tests and diagnostic tests were documented. Costs and MLHFQ scores in patients with or without hypertension, diabetes and renal impairment were compared. RESULTS: A total of 73 HFpEF patients were included. It was found that loop diuretics (93.1%, 78.1%) was the most frequently used agent for HFpEF management in both in-patient and out-patient settings. The mean 1-year direct medical cost was USD$ 19969 (1 US $ = 7.8 HK$), with in-patient ward care contributing to the largest proportion (72.2%) of the total cost. Patients with diabetes or renal impairment were associated with a higher cost of HFpEF management. Significant difference was found in the renal impairment group (median cost: USD$ 24604.2 versus USD$ 12706.8 in no impairment group, p = 0.023). The MLHFQ scores of the subjects improved significantly during the study period (p < 0.0005). CONCLUSIONS: The cost of management of HFpEF was enormous and further increased in the presence of comorbidities.


Asunto(s)
Fármacos Cardiovasculares/uso terapéutico , Costos Directos de Servicios , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/economía , Adulto , Anciano , Anciano de 80 o más Años , Complicaciones de la Diabetes , Diuréticos/uso terapéutico , Femenino , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/fisiopatología , Hong Kong , Hospitales Públicos , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Calidad de Vida , Insuficiencia Renal/complicaciones , Estudios Retrospectivos , Volumen Sistólico , Resultado del Tratamiento
8.
J Endourol ; 38(5): 505-512, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38482817

RESUMEN

Background: The narrower focal zone (FZ) size of modern lithotripter was considered as one of the factors that resulted in suboptimal treatment result of extracorporeal shockwave lithotripsy (SWL). Therefore, we investigate the efficacy and safety of standard narrow or extended (FZ) sizes in SWL for patients with renal stones. Materials and Methods: In this prospective study conducted between April 2018 and October 2022, patients with renal stones were randomized to receive SWL with either standard or extended FZ. Treatment was delivered using a Modulith SLX-F2 lithotripter with a maximum of 3000 shocks at 1.5 Hz. The primary outcome was treatment success 12 weeks after a single SWL session, defined as the absence of a stone or stone fragment <4 mm on computed tomography. Secondary outcomes included the incidence of perinephric hematoma, stone-free rate (SFR), and changes in the urinary levels of acute renal injury markers. Results: A total of 320 patients were recruited, and 276 patients were randomized into the two groups. The two groups had similar baseline parameters. The treatment success rate was significantly better for standard FZ (74.3%) than the extended FZ group (59.3%) (p = 0.009). Standard FZ also had a significantly better SFR (Grade-A, 36.8% vs 23.0%, p = 0.013) and less pain after treatment. Both groups had similar perinephric hematoma formation rates, unplanned hospital admission rates, and changes in urinary acute renal injury markers. Conclusions: The standard narrow FZ has better treatment efficacy and similar safety compared with the extended FZ during SWL for renal stones. This clinical trial has been registered in the public domain (CCRBCTR) under trial number CUHK_CCRB00510.


Asunto(s)
Cálculos Renales , Litotricia , Humanos , Cálculos Renales/terapia , Litotricia/efectos adversos , Litotricia/métodos , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Resultado del Tratamiento , Adulto , Riñón , Anciano , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia
9.
Neurol Educ ; 2(4): e200103, 2023 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-39359316

RESUMEN

Game-based learning (GBL) has emerged as a promising approach to engage students and promote deep learning in a variety of educational settings. Neurology and neuroscience are complex fields that require an understanding of intricate neural structures and their functional roles. GBL can support the acquisition and application of such knowledge. In this article, we give an overview of the current state of GBL in neuroscience education. First, we review the language of gaming, establishing conceptual definitions for game elements, gamification, serious games, and GBL. Second, we discuss a literature review of games in the educational literature for adult learners involved in neuroscience. Third, we review available games intended for neuroscience education. Finally, we share tips for educators interested in developing their own educational games. By leveraging the unique features of games, including interactivity, feedback, and immersive experiences, educators and learners can engage with complex neuroscience concepts in a fun, engaging, and effective way.

10.
Am J Respir Cell Mol Biol ; 43(6): 674-83, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20081051

RESUMEN

Peroxisome proliferator-activated receptor (PPAR)-α and PPARγ participate in cell proliferation and apoptosis. Few studies have simultaneously investigated both PPARα and PPARγ in lung cancers in vivo. The roles of PPARα and -γ were investigated in the development of pulmonary tumors induced in the adult A/J mouse by treatment with 4-(methylnitrosamino)-l-(3-pyridyl)-lbutanone (NNK). Compared with the normal lung tissues, PPARγ expression was much higher in the NNK-induced lung tumor tissues. However, PPARγ transcriptional activity, and the levels of two major endogenous PPARγ ligands, 13-hydroxyoctadecadienoic acid and 15-hydroxyeicosatetraenoic acid, were significantly lower in the NNK-treated lung tissues. The ligand changes in mice were confirmed in human lung cancer tissues. Along with the alteration of PPARγ and its endogenous ligands, the level of PPARα and its activity were increased in the NNK-induced mouse lung tumors. Treatment of mice with the synthetic PPARγ ligand, pioglitazone, significantly inhibited the formation of mouse lung tumors induced by NNK. Our study demonstrated that the reduction of endogenous PPARγ ligands and increased PPARα occurred before the formation of lung tumors, indicating that the molecular changes play a role in lung carcinogenesis. The results suggest that the enhancement of PPARγ activity with its ligands, and the suppression of PPARα with its inhibitors, may prevent the formation of lung tumors, as well as accelerate the therapy of lung cancer. Our findings may also reveal the possibility of using the level of endogenous PPARγ ligands and the activities of PPARγ or PPARα as tumor markers for lung cancer.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , PPAR alfa/metabolismo , PPAR gamma/metabolismo , Lesiones Precancerosas/patología , Animales , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Ácidos Hidroxieicosatetraenoicos/metabolismo , Ligandos , Ácidos Linoleicos/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Metabolismo de los Lípidos/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Ratones , Nitrosaminas , PPAR alfa/genética , PPAR gamma/genética , Pioglitazona , Lesiones Precancerosas/genética , Lesiones Precancerosas/metabolismo , Receptor alfa X Retinoide/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Tiazolidinedionas/farmacología , Transcripción Genética/efectos de los fármacos
11.
J Cell Biol ; 170(2): 305-16, 2005 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-16009726

RESUMEN

Gab proteins amplify and integrate signals stimulated by many growth factors. In culture and animals, retinoic acid (RA) induces neuronal differentiation. We show that Gab2 expression is detected in neurons in three models of neuronal differentiation: embryonic carcinoma (EC) stem cells, embryonic stem cells, and primary neural stem cells (NSCs). RA treatment induces apoptosis, countered by basic FGF (bFGF). In EC cells, Gab2 silencing results in hypersensitivity to RA-induced apoptosis and abrogates the protection by bFGF. Gab2 suppression reduces bFGF-dependent activation of AKT but not ERK, and constitutively active AKT, but not constitutively active MEK1, reverses the hypersensitization. Thus, Gab2-mediated AKT activation is required for bFGF's protection. Moreover, Gab2 silencing impairs the differentiation of EC cells to neurons. Similarly, in NSCs, Gab2 suppression reduces bFGF-dependent proliferation as well as neuronal survival and production upon differentiation. Our findings provide the first evidence that Gab2 is an important player in neural differentiation, partly by acting downstream of bFGF to mediate survival through phosphoinositide 3 kinase-AKT.


Asunto(s)
Factor 2 de Crecimiento de Fibroblastos/fisiología , Neuronas/citología , Fosfoproteínas/fisiología , Tretinoina/fisiología , Proteínas Adaptadoras Transductoras de Señales , Animales , Apoptosis , Diferenciación Celular , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Embrión de Mamíferos/citología , Activación Enzimática , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , MAP Quinasa Quinasa 1/metabolismo , Ratones , Neuronas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfoproteínas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Células Madre/citología , Células Madre/metabolismo , Tretinoina/farmacología
12.
Electrophoresis ; 30(3): 457-64, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19148904

RESUMEN

Fluorescence anisotropy (FA), non-equilibrium CE of equilibrium mixtures (NECEEM) and high-speed CE were evaluated for measuring dissociation kinetics of peptide-protein binding systems. Fyn-SH3-SH2, a protein construct consisting of the src homology 2 (SH2) and 3 (SH3) domain of the protein Fyn, and a fluorescein-labeled phosphopeptide were used as a model system. All three methods gave comparable half-life of approximately 53 s for Fyn-SH3-SH2:peptide complex. Achieving satisfactory results by NECEEM required columns over 30 cm long. When using Fyn-SH2-SH3 tagged with glutathione S-transferase (GST) as the binding protein, both FA and NECEEM assays gave evidence of two complexes forming with the peptide, yet neither method allowed accurate measurement of dissociation rates for both complexes because of a lack of resolution. High-speed CE, with a 7 s separation time, enabled separation of both complexes and allowed determination of dissociation rate of both complexes independently. The two complexes had half-lives of 22.0+/-2.7 and 58.8+/-6.1 s, respectively. Concentration studies revealed that the GST-Fyn-SH3-SH2 protein formed a dimer so that complexes had binding ratios of 2:1 (protein-to-peptide ratio) and 2:2. Our results demonstrate that although all methods are suitable for 1:1 binding systems, high-speed CE is unique in allowing multiple complexes to be resolved simultaneously. This property allows determination of binding kinetics of complicated systems and makes the technique useful for discovering novel affinity interactions.


Asunto(s)
Electroforesis Capilar/métodos , Proteínas Proto-Oncogénicas c-fyn/química , Dominios Homologos src , Sitios de Unión , Polarización de Fluorescencia , Glutatión Transferasa/química , Glutatión Transferasa/metabolismo , Cinética , Unión Proteica , Proteínas Proto-Oncogénicas c-fyn/análisis , Proteínas Proto-Oncogénicas c-fyn/metabolismo , Transducción de Señal
13.
J Exp Clin Cancer Res ; 38(1): 359, 2019 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-31420013

RESUMEN

BACKGROUND: Epidemiological observations have demonstrated that ambient fine particulate matter with dp < 2.5 µm (PM2.5) as the major factor responsible for the increasing incidence of lung cancer in never-smokers. However, there are very limited experimental data to support the association of PM2.5 with lung carcinogenesis and to compare PM2.5 with smoking carcinogens. METHODS: To study whether PM2.5 can contribute to lung tumorigenesis in a way similar to smoking carcinogen 4-methylnitrosamino-l-3-pyridyl-butanone (NNK) via 15-lipoxygenases (15-LOXs) reduction, normal lung epithelial cells and cancer cells were treated with NNK or PM2.5 and then epigenetically and post-translationally examined the cellular and molecular profiles of the cells. The data were verified in lung cancer samples and a mouse lung tumor model. RESULTS: We found that similar to smoking carcinogen NNK, PM2.5 significantly enhanced cell proliferation, migration and invasion, but reduced the levels of 15-lipoxygenases-1 (15-LOX1) and 15-lipoxygenases-2 (15-LOX2), both of which were also obviously decreased in lung cancer tissues. 15-LOX1/15-LOX2 overexpression inhibited the oncogenic cell functions induced by PM2.5/NNK. The tumor formation and growth were significantly higher/faster in mice implanted with PM2.5- or NNK-treated NCI-H23 cells, accompanied with a reduction of 15-LOX1/15-LOX2. Moreover, 15-LOX1 expression was epigenetically regulated at methylation level by PM2.5/NNK, while both 15-LOX1 and 15-LOX2 could be significantly inhibited by a set of PM2.5/NNK-mediated microRNAs. CONCLUSION: Collectively, PM2.5 can function as the smoking carcinogen NNK to induce lung tumorigenesis by inhibiting 15-LOX1/15-LOX2.


Asunto(s)
Araquidonato 15-Lipooxigenasa/química , Carcinogénesis/patología , Neoplasias Pulmonares/patología , Material Particulado/efectos adversos , Animales , Apoptosis , Biomarcadores de Tumor/metabolismo , Carcinogénesis/inducido químicamente , Carcinogénesis/metabolismo , Estudios de Casos y Controles , Movimiento Celular , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inhibidores de la Lipooxigenasa/efectos adversos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/etiología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nitrosaminas/toxicidad , Pronóstico , Fumar/efectos adversos , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
14.
PLoS Comput Biol ; 3(4): e63, 2007 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-17411336

RESUMEN

The MYC genes encode nuclear sequence specific-binding DNA-binding proteins that are pleiotropic regulators of cellular function, and the c-MYC proto-oncogene is deregulated and/or mutated in most human cancers. Experimental studies of MYC binding to the genome are not fully consistent. While many c-MYC recognition sites can be identified in c-MYC responsive genes, other motif matches-even experimentally confirmed sites-are associated with genes showing no c-MYC response. We have developed a computational model that integrates multiple sources of evidence to predict which genes will bind and be regulated by MYC in vivo. First, a Bayesian network classifier is used to predict those c-MYC recognition sites that are most likely to exhibit high-occupancy binding in chromatin immunoprecipitation studies. This classifier incorporates genomic sequence, experimentally determined genomic chromatin acetylation islands, and predicted methylation status from a computational model estimating the likelihood of genomic DNA methylation. We find that the predictions from this classifier are also applicable to other transcription factors, such as cAMP-response element-binding protein, whose binding sites are sensitive to DNA methylation. Second, the MYC binding probability is combined with the gene expression profile data from nine independent microarray datasets in multiple tissues. Finally, we may consider gene function annotations in Gene Ontology to predict the c-MYC targets. We assess the performance of our prediction results by comparing them with the c-myc targets identified in the biomedical literature. In total, we predict 460 likely c-MYC target genes in the human genome, of which 67 have been reported to be both bound and regulated by MYC, 68 are bound by MYC, and another 80 are MYC-regulated. The approach thus successfully identifies many known c-MYC targets and suggests many novel sites. Our findings suggest that to identify c-MYC genomic targets, integration of different data sources helps to improve the accuracy.


Asunto(s)
Cromatina/química , Cromatina/genética , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Perfilación de la Expresión Génica/métodos , Modelos Biológicos , Análisis de Secuencia de Proteína/métodos , Factores de Transcripción/química , Factores de Transcripción/genética , Sitios de Unión , Mapeo Cromosómico , Simulación por Computador , Modelos Químicos , Unión Proteica , Mapeo de Interacción de Proteínas , Proto-Oncogenes Mas , Relación Estructura-Actividad , Integración de Sistemas
15.
OMICS ; 11(1): 96-115, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17411398

RESUMEN

Gene expression responses are complex and frequently involve the actions of many genes to effect coordinated patterns. We hypothesized these coordinated responses are evolutionarily conserved and used a comparison of human and mouse gene expression profiles to identify the most prominent conserved features across a set of normal mammalian tissues. Based on data from multiple studies across multiple tissues in human and mouse, 13 gene expression modes across multiple tissues were identified in each of these species using principal component analysis. Strikingly, 1-to-1 pairing of human and mouse modes was observed in 12 out of 13 modes obtained from the two species independently. These paired modes define evolutionarily conserved gene expression response modes (CGEMs). Notably, in this study we were able to extract biological responses that are not overwhelmed by laboratory-to-laboratory or species-to-species variation. Of the variation in our gene expression dataset, 84% can be explained using these CGEMs. Functional annotation was performed using Gene Ontology, pathway, and transcription factor binding site over representation. Our conclusion is that we found an unbiased way of obtaining conserved gene response modes that accounts for a considerable portion of gene expression variation in a given dataset, as well as validates the conservation of major gene expression response modes across the mammals.


Asunto(s)
Perfilación de la Expresión Génica , Animales , Sitios de Unión , Análisis por Conglomerados , Secuencia Conservada , Evolución Molecular , Regulación de la Expresión Génica , Humanos , Ratones , Modelos Estadísticos , Análisis de Secuencia por Matrices de Oligonucleótidos , Análisis de Componente Principal , Especificidad de la Especie , Factores de Transcripción/metabolismo
16.
Pediatr Neurol ; 33(5): 337-44, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16243221

RESUMEN

In this open-label study, the safety, tolerability, and pharmacokinetics of oxcarbazepine as monotherapy or adjunctive therapy were studied in infants and young children with partial seizures. In a 30-day treatment phase, oxcarbazepine was titrated from 10 mg/kg/day to 60 mg/kg/day. Blood samples for analysis of the oxcarbazepine metabolite, the 10-monohydroxy derivative (MHD), were obtained at regular intervals. Patients completing the treatment phase entered a 6-month extension phase. Safety and tolerability were assessed throughout the study. Twenty-four patients (mean [range] age, 20.4 [2-45] months) were enrolled. Nineteen (79%) patients completed the treatment phase and, together with one patient who discontinued prematurely during the treatment phase, entered the extension phase. Thirteen of 20 (65%) patients completed the extension phase. The most common adverse events were pyrexia, ear infection, and irritability. Whether patients (n = 23) received enzyme-inducing antiepileptic drugs or not, MHD concentrations were consistent with those predicted from a linear, one-compartment, population-pharmacokinetic model based on a model previously fitted for 3- to 17-year-old children. Oxcarbazepine was safe and well tolerated in infants and young children. The pharmacokinetic profile of MHD was predicted by extension of a model based on older children.


Asunto(s)
Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/farmacocinética , Carbamazepina/análogos & derivados , Epilepsias Parciales/tratamiento farmacológico , Anticonvulsivantes/efectos adversos , Carbamazepina/administración & dosificación , Carbamazepina/efectos adversos , Carbamazepina/farmacocinética , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Oxcarbazepina , Resultado del Tratamiento
17.
J Mol Med (Berl) ; 93(11): 1221-33, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26041383

RESUMEN

UNLABELLED: Smoking carcinogen N-nitrosamines such as 4-methylnitrosamino-l-3-pyridyl-butanone (NNK) require metabolic activation to exert their genotoxicity. The first activation step is mainly catalyzed by cytochrome P450 (CYP) family. Estrogen receptor α (ERα) plays a role in lung pathology. The association between them is unknown. In this study, we explored the relationship and function of CYP1B1 and ERα in NNK-induced lung tumorigenesis. CYP1B1 and ERα expression was analyzed in human lung cancer tissues and NNK-induced lung tumor of A/J mice. Cell lines NCI-H23 and NCI-H460 were employed to further study the responsible mechanisms using various cellular and molecular approaches. Our in vivo experiments demonstrated that CYP1B1 and ERα were over-expressed at the early stage of NNK-induced lung tumorigenesis. Microarray analysis found that ERα was involved in the extracellular-signal-regulated kinase (ERK)/MAPK pathway. NNK activated RAS/ERK/AP1 as it remarkably increased the levels of p-ERK, c-Fos, and c-Jun but inhibited multiple negative regulators of Ras/ERK/AP1, Pdcd4, Spry1, Spry2, and Btg2 through up-regulating miR-21. Both CYP1B1 siRNA and ERK-specific inhibitor U0126 suppressed NNK-mediated ERα up-regulation, suggesting that ERα was downstream of CYP1B1 and ERK. ERK inactivation led to the accumulation of CYP1B1, indicating that CYP1B1 was upstream of ERK activation. Inhibition of ERK or ERα decreased NNK-induced cell proliferation. Blockage of CYP1B1 or ERα induced apoptosis of lung cancer cells. Collectively, NNK-mediated ERα induction is via CYP1B1 and ERK and contributes to the lung carcinogenesis. The inhibition of CYP1B1, ERK, or ERα may arrest the lung cancer cell growth, implicating a pivotal strategy for the treatment of lung cancer. KEY MESSAGES: Smoking carcinogen NNK requires metabolic activation to exert their genotoxicity. CYP1B1 is the enzyme to catalyze NNK. NNK activates CYP1B1 and ERK to induce ERα. Inhibition of CYP1B1, ERK, or ERα arrests the lung cancer cell growth.


Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Receptor alfa de Estrógeno/metabolismo , Neoplasias Pulmonares/patología , Sistema de Señalización de MAP Quinasas , Animales , Línea Celular , Humanos , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/fisiopatología , Neoplasias Pulmonares/terapia , Ratones , Nitrosaminas/farmacología
18.
Arch Surg ; 136(10): 1131-5, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11585504

RESUMEN

HYPOTHESIS: The digital exploration of stab wounds in the left thoracoabdominal region allows the early diagnosis of diaphragmatic lesions. DESIGN: Diagnostic test study. The digital exploration of the diaphragm was compared with laparotomy (the gold standard) and thoracoscopy. SETTING: The study setting was the Hospital Universitario San Vicente de Paúl (Medellín, Colombia). This is a referral trauma center for the general community. PATIENTS: The study included 82 consecutive patients who were admitted to our institution during a 12-month period with injuries caused by stab wounds to the left thoracoabdominal region and who did not have indications for immediate surgery. Digital exploration of the wound was performed by the attending surgeon in the emergency department. If a lesion of the diaphragm was identified, a laparotomy was performed; if no diaphragmatic lesion was found, a diagnostic left thoracoscopy and/or laparotomy was performed. Results of the laparotomy (n = 63) or thoracoscopy (n = 19) were used as the standard of reference for the determination of sensitivity, specificity, and predictive values of digital exploration. INTERVENTION: The integrity of the diaphragm was determined by digital exploration through the stab wound. MAIN OUTCOME MEASURES: Sensitivity, specificity, predictive value, and likelihood ratio were calculated. RESULTS: For the detection of diaphragmatic lesions, digital exploration demonstrated a sensitivity of 96%, a specificity of 83.3%, a positive predictive value of 91%, and a negative predictive value of 93.7%. CONCLUSION: Digital exploration is a reliable method for the detection of injuries to the left side of the diaphragm caused by stab wounds.


Asunto(s)
Diafragma/lesiones , Palpación , Heridas Punzantes/diagnóstico , Adolescente , Adulto , Diafragma/cirugía , Femenino , Humanos , Laparotomía , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Toracoscopía , Heridas Punzantes/cirugía
19.
J Child Neurol ; 28(12): 1607-17, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23143728

RESUMEN

Early infantile epileptic encephalopathy or Ohtahara syndrome is the earliest form of the age-dependent epileptic encephalopathies. Its manifestations include tonic spasms, focal motor seizures, suppression burst pattern, pharmaco-resistance, and dismal prognosis. The purpose of this study was to evaluate the effectiveness of epilepsy surgery in selected infants. We identified 11 patients, 9 from the literature and 2 from our institution that fulfilled diagnostic criteria of Ohtahara syndrome and had undergone epilepsy surgery in infancy. Seven of the 11 infants have remained seizure free (Engel class IA) and four are reportedly having rare to infrequent seizures (Engel class IIB). All patients experienced "catch up" development. In contrast to Ohtahara's15 pharmacotherapy managed patients, who had a mortality rate of approximately fifty percent, and those that survived continued to have seizures and were severely impaired, the outcome of selected surgically managed patients is much more favorable.


Asunto(s)
Neurocirugia , Espasmos Infantiles/cirugía , Electroencefalografía , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética
20.
Pediatr Neurol ; 48(2): 143-5, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23337009

RESUMEN

We report a patient with Sturge-Weber syndrome without facial angioma, who presented with seizures and normal initial imaging results. The patient experienced several years without seizures before a sudden increase in seizure frequency, followed by an atypical evolution of imaging findings prompting biopsy to establish the diagnosis. This case highlights not only the rare presentation of isolated leptomeningeal angiomatosis, but also the potential for atypical evolution of imaging findings through the course of the disease. We detail the imaging findings of our case and review the potential pathophysiological basis for this appearance. Our experience suggests that repeat imaging is warranted in patients with suspected Sturge-Weber syndrome or those with intractable cryptogenic epilepsy, because some imaging features of Sturge-Weber syndrome may manifest over time.


Asunto(s)
Encéfalo/patología , Convulsiones/patología , Síndrome de Sturge-Weber/patología , Humanos , Lactante , Masculino , Convulsiones/etiología , Síndrome de Sturge-Weber/complicaciones
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