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1.
Artigo em Inglês | MEDLINE | ID: mdl-38865224

RESUMO

With the growing complexity and volume of data, visualizations have become more intricate, often requiring advanced techniques to convey insights. These complex charts are prevalent in everyday life, and individuals who lack knowledge in data visualization may find them challenging to understand. This paper investigates using Large Language Models (LLMs) to help users with low data literacy understand complex visualizations. While previous studies focus on text interactions with users, we noticed that visual cues are also critical for interpreting charts. We introduce an LLM application that supports both text and visual interaction for guiding chart interpretation. Our study with 26 participants revealed that the in-situ support effectively assisted users in interpreting charts and enhanced learning by addressing specific chart-related questions and encouraging further exploration. Visual communication allowed participants to convey their interests straightforwardly, eliminating the need for textual descriptions. However, the LLM assistance led users to engage less with the system, resulting in fewer insights from the visualizations. This suggests that users, particularly those with lower data literacy and motivation, may have over-relied on the LLM agent. We discuss opportunities for deploying LLMs to enhance visualization literacy while emphasizing the need for a balanced approach.

2.
IEEE Trans Vis Comput Graph ; 28(1): 184-194, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34587042

RESUMO

Charts go hand in hand with text to communicate complex data and are widely adopted in news articles, online blogs, and academic papers. They provide graphical summaries of the data, while text explains the message and context. However, synthesizing information across text and charts is difficult; it requires readers to frequently shift their attention. We investigated ways to support the tight coupling of text and charts in data documents. To understand their interplay, we analyzed the design space of chart-text references through news articles and scientific papers. Informed by the analysis, we developed a mixed-initiative interface enabling users to construct interactive references between text and charts. It leverages natural language processing to automatically suggest references as well as allows users to manually construct other references effortlessly. A user study complemented with algorithmic evaluation of the system suggests that the interface provides an effective way to compose interactive data documents.

3.
IEEE Trans Vis Comput Graph ; 26(1): 227-237, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514138

RESUMO

Facetto is a scalable visual analytics application that is used to discover single-cell phenotypes in high-dimensional multi-channel microscopy images of human tumors and tissues. Such images represent the cutting edge of digital histology and promise to revolutionize how diseases such as cancer are studied, diagnosed, and treated. Highly multiplexed tissue images are complex, comprising 109 or more pixels, 60-plus channels, and millions of individual cells. This makes manual analysis challenging and error-prone. Existing automated approaches are also inadequate, in large part, because they are unable to effectively exploit the deep knowledge of human tissue biology available to anatomic pathologists. To overcome these challenges, Facetto enables a semi-automated analysis of cell types and states. It integrates unsupervised and supervised learning into the image and feature exploration process and offers tools for analytical provenance. Experts can cluster the data to discover new types of cancer and immune cells and use clustering results to train a convolutional neural network that classifies new cells accordingly. Likewise, the output of classifiers can be clustered to discover aggregate patterns and phenotype subsets. We also introduce a new hierarchical approach to keep track of analysis steps and data subsets created by users; this assists in the identification of cell types. Users can build phenotype trees and interact with the resulting hierarchical structures of both high-dimensional feature and image spaces. We report on use-cases in which domain scientists explore various large-scale fluorescence imaging datasets. We demonstrate how Facetto assists users in steering the clustering and classification process, inspecting analysis results, and gaining new scientific insights into cancer biology.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Neoplasias , Redes Neurais de Computação , Análise por Conglomerados , Humanos , Neoplasias/classificação , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Fenótipo , Software , Biologia de Sistemas
4.
J Int Neuropsychol Soc ; 15(6): 990-1001, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19709452

RESUMO

Decision making in an emotionally conflicting situation is important in social life. We aimed to address the similarity and disparity of neural correlates involved in processing ambivalent stimuli in patients with schizophrenia and patients with depression. Behavioral task-related hemodynamic responses were measured using [15O]H2O positron emission tomography (PET) in 12 patients with schizophrenia and 12 patients with depression. The task was a modified word-stem completion task, which was designed to evoke ambivalence in forced and non-forced choice conditions. The prefrontal cortex and the cerebellum were found to show increased activity in the healthy control group. In the schizophrenia group, activity in these two regions was negligible. In the depression group, the pattern of activity was altered and a functional compensatory recruitment of the inferior parietal regions was suggested. The prefrontal cortex seems to be associated with the cognitive control to resolve the conflict toward the ambivalent stimuli, whereas the cerebellum reflects the sustained working memory to search for compromise alternatives. The deficit of cerebellar activation in the schizophrenia group might underlie the inability to search and consider compromising responses for conflict resolution.


Assuntos
Tomada de Decisões/fisiologia , Depressão/diagnóstico por imagem , Depressão/fisiopatologia , Esquizofrenia/diagnóstico por imagem , Psicologia do Esquizofrênico , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Mapeamento Encefálico , Comportamento de Escolha/fisiologia , Compreensão/fisiologia , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Testes Neuropsicológicos , Isótopos de Oxigênio , Tomografia por Emissão de Pósitrons/métodos , Esquizofrenia/fisiopatologia , Estatística como Assunto , Água , Adulto Jovem
5.
Psychiatry Res ; 170(2-3): 267-70, 2009 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-19880196

RESUMO

We explored the affective processing of patients with alcohol dependence to emotionally stimulating written words and pictures. The alcoholic group demonstrated dichotomous responses and was incapable of compromising in neutral conditions. The dichotomous response pattern and positivity offset differed between words and pictures in patients with alcohol dependence.


Assuntos
Afeto/fisiologia , Alcoolismo/fisiopatologia , Alcoolismo/psicologia , Reconhecimento Visual de Modelos/fisiologia , Vocabulário , Adulto , Análise de Variância , Discriminação Psicológica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estimulação Luminosa/métodos , Tempo de Reação/fisiologia
6.
Cytokine ; 42(1): 121-7, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18289868

RESUMO

Interleukin (IL)-32 was recently identified as a new cytokine which induces various proinflammatory cytokines in human monocytes and macrophages. Therefore, IL-32 has been primarily studied in inflammatory models such as rheumatoid arthritis and inflammatory bowel diseases. The regulation of endogenous IL-32 in other immune cells remains unknown. In the present study, we stimulated Jurkat T cells with phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA) and examined IL-32 expression at both the mRNA and protein levels. All mRNAs of the four IL-32 isoforms and the 12-15 kDa IL-32 protein were independent of PHA and PMA stimulation, however a 9 kDa molecular weight IL-32 protein in the cell culture supernatant was induced by PHA and PMA after 16 h of stimulation. Compared to other human cell lines, the Jurkat cell line constitutively expressed a 12-15 kDa molecule of IL-32, which is smaller than the known IL-32 isoforms. We used IL-32 shRNA to examine the specificity of the 12-15 kDa molecule. Upon IL-32 shRNA transfection, the 12-15 kDa band was decreased specifically as compared to the control scrambled clone. Thus, the constitutive expression of IL-32 mRNA as well as the predominant production of a smaller sized IL-32 isoform in Jurkat cells may implicate a role for IL-32 in human T cell leukemia.


Assuntos
Interleucinas/metabolismo , Células Jurkat , Animais , Humanos , Interleucinas/genética , Mieloblastina/metabolismo , Fito-Hemaglutininas/imunologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Linfócitos T/imunologia , Acetato de Tetradecanoilforbol/imunologia
7.
IEEE Trans Vis Comput Graph ; 24(1): 595-604, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28866524

RESUMO

In this paper, we present story curves, a visualization technique for exploring and communicating nonlinear narratives in movies. A nonlinear narrative is a storytelling device that portrays events of a story out of chronological order, e.g., in reverse order or going back and forth between past and future events. Many acclaimed movies employ unique narrative patterns which in turn have inspired other movies and contributed to the broader analysis of narrative patterns in movies. However, understanding and communicating nonlinear narratives is a difficult task due to complex temporal disruptions in the order of events as well as no explicit records specifying the actual temporal order of the underlying story. Story curves visualize the nonlinear narrative of a movie by showing the order in which events are told in the movie and comparing them to their actual chronological order, resulting in possibly meandering visual patterns in the curve. We also present Story Explorer, an interactive tool that visualizes a story curve together with complementary information such as characters and settings. Story Explorer further provides a script curation interface that allows users to specify the chronological order of events in movies. We used Story Explorer to analyze 10 popular nonlinear movies and describe the spectrum of narrative patterns that we discovered, including some novel patterns not previously described in the literature. Feedback from experts highlights potential use cases in screenplay writing and analysis, education and film production. A controlled user study shows that users with no expertise are able to understand visual patterns of nonlinear narratives using story curves.

8.
J Pharm Pharmacol ; 59(1): 123-30, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17227629

RESUMO

In this study, we aimed to investigate the anti-inflammatory activity, antinociceptive activity and the action mechanism of Trachelospermi caulis extract. The anti-inflammatory effects were investigated using arachidonic acid, 12-O-tetradecanoylphorbol 13-acetate or carrageenan-induced oedema assays. Antinociceptive activity, using the acetic acid-induced writhing model, was also tested in mice. The extract exhibited dose-dependent and significant (P<0.05 at 100-400 mg kg-1) anti-inflammatory and antinociceptive activity in the animals. To further understand the mechanism of activity, we investigated whether the extract inhibited the expression of inducible nitric oxide synthase (iNOS), the production of nitric oxide (NO) and the expression of TNF-alpha from murine macrophage RAW 264.7 cells. Similar to the in-vivo activity, the iNOS expression, NO production and TNF-alpha expression were found to be dose dependent and significantly suppressed by the extract through the inhibition of the p38 MAP kinase/NF-kappaB pathway. Taken together, the results presented here suggest that T. caulis extract may be useful for the treatment of various inflammatory diseases.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Dor/tratamento farmacológico , Extratos Vegetais/farmacologia , Ácido Acético , Animais , Ácido Araquidônico , Carragenina , Linhagem Celular , Edema/induzido quimicamente , Etanol/química , Furanos/análise , Glucosídeos/análise , Masculino , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Dor/induzido quimicamente , Extratos Vegetais/análise , Ratos , Ratos Wistar , Acetato de Tetradecanoilforbol , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
J Ethnopharmacol ; 112(1): 49-54, 2007 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-17395412

RESUMO

The extract of Pyrolae herba (PH), which has been used as an anti-inflammatory folk remedy in Korea and China, was investigated for its anti-inflammatory action using arachidonic acid, 12-O-tetradecanoylphorbol 13-acetate or carrageenan-induced edema assays. The anti-nociceptive activity of PH was also tested in mice using the acetic acid-induced writhing model. PH showed dose-dependent and significant (P<0.05 at 100-400mg/kg) anti-inflammatory and anti-nociceptive activities in the animal assays. The mechanism of the activities of PH was examined by testing the extract to determine if it inhibits the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) from the murine macrophages, RAW 264.7 cells. Similar to the in vivo activities, both the iNOS expression and NO production were significantly suppressed by PH in a dose-dependent manner. PH also inhibited the activating phosphorylation of p38 MAP kinase and NF-kappaB in these cells. These results provide a scientific basis to explain the effects of PH as an anti-inflammatory folk remedy in Asian countries.


Assuntos
Anti-Inflamatórios/farmacologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico/antagonistas & inibidores , Pyrola , Animais , Linhagem Celular , China , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Edema/tratamento farmacológico , Edema/patologia , Coreia (Geográfico) , Macrófagos/metabolismo , Masculino , Medicina Tradicional do Leste Asiático , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/biossíntese , Extratos Vegetais , Ratos , Ratos Wistar
10.
Clin Psychopharmacol Neurosci ; 15(3): 222-228, 2017 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-28783930

RESUMO

OBJECTIVE: This study aimed to investigate the association between the synaptosomal-associated protein 25 kDa (SNAP-25) genotype and performance on the continuous performance test (CPT) in Korean children with attention-deficit/hyperactivity disorder (ADHD). METHODS: Eighty-seven children with ADHD (mean age, 9.23±1.99 years) participated in this study. Omission errors, commission errors, reaction time, and reaction time variability on the CPT were analyzed. The single-nucleotide polymorphism (SNP) rs3746544 (1065 T>G) of SNAP-25 was genotyped to examine the association with CPT performance. RESULTS: We found significantly more omission errors on the CPT among children with the TT genotype of SNAP-25 (t=2.56, p=0.012) after correcting for multiple testing. CONCLUSION: Our results suggest the possible involvement of the SNAP-25 1065 T>G polymorphism in the inattention phenotype in children with ADHD. Further studies with more refined neuropsychological measures and much larger sample sizes are needed to confirm our findings.

11.
IEEE Trans Vis Comput Graph ; 23(1): 491-500, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27875165

RESUMO

In recent years, there is a growing need for communicating complex data in an accessible graphical form. Existing visualization creation tools support automatic visual encoding, but lack flexibility for creating custom design; on the other hand, freeform illustration tools require manual visual encoding, making the design process time-consuming and error-prone. In this paper, we present Data-Driven Guides (DDG), a technique for designing expressive information graphics in a graphic design environment. Instead of being confined by predefined templates or marks, designers can generate guides from data and use the guides to draw, place and measure custom shapes. We provide guides to encode data using three fundamental visual encoding channels: length, area, and position. Users can combine more than one guide to construct complex visual structures and map these structures to data. When underlying data is changed, we use a deformation technique to transform custom shapes using the guides as the backbone of the shapes. Our evaluation shows that data-driven guides allow users to create expressive and more accurate custom data-driven graphics.

12.
J Pharm Pharmacol ; 58(4): 503-12, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16597368

RESUMO

The effect of extracts from various Oriental medicinal herbs on mast-cell-mediated allergic reactions was investigated in this study. Of these extracts, the medicinal herb Rubiae Radix exhibited the most potent activity in the cells, with an IC50 value (concentration necessary to obtain 50% inhibition of the response) of approximately 35 +/- 2.1 microg mL(-1), and its inhibition of compound-48/80-induced systemic anaphylaxis by 48.6 +/- 8.5% at 300 mg kg(-1) in mice. It also inhibited the expression of the pro-inflammatory mediator tumour necrosis factor-alpha (TNF-alpha). As for its mechanism of action, Rubiae Radix suppressed the activating phosphorylation of Syk, a key enzyme in mast-cell signalling processes, and that of Akt in a dose-dependent manner. It also inhibited the MAP kinase ERK1/2, which is critical for the production of inflammatory cytokines in mast cells, as indicated by the suppression of the activating phosphorylation of ERK1/2. These results suggest that Rubiae Radix suppresses the activation of mast cells through the inhibition of Syk for anti-allergic activity.


Assuntos
Antialérgicos/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Mastócitos/efeitos dos fármacos , Mastócitos/enzimologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Rubia , Animais , Antialérgicos/isolamento & purificação , Linhagem Celular , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Raízes de Plantas , Proteínas Tirosina Quinases/metabolismo , Quinase Syk
13.
Int Clin Psychopharmacol ; 31(5): 265-74, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27276401

RESUMO

α-Lipoic acid (ALA) has been reported to be effective in reducing body weight in rodents and obese patients. Our previous open trial showed that ALA may play a role in reducing weight gain in patients with schizophrenia on atypical antipsychotics. The present study evaluated the efficacy of ALA in reducing weight and BMI in patients with schizophrenia who had experienced significant weight gain since taking atypical antipsychotics. In a 12-week, double-blind randomized placebo-controlled study, 22 overweight and clinically stable patients with schizophrenia were randomly assigned to receive ALA or placebo. ALA was administered at 600-1800 mg, as tolerated. Weight, BMI, abdomen fat area measured by computed tomography, and metabolic values were determined. Adverse effects were also assessed to examine safety. Overall, 15 patients completed 12 weeks of treatment. There was significant weight loss and decreased visceral fat levels in the ALA group compared with the placebo group. There were no instances of psychopathologic aggravation or severe ALA-associated adverse effects. ALA was effective in reducing weight and abdominal obesity in patients with schizophrenia who had experienced significant weight gain since beginning an atypical antipsychotic regimen. Moreover, ALA was well tolerated throughout this study. ALA might play an important role as an adjunctive treatment in decreasing obesity in patients who take atypical antipsychotics.


Assuntos
Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Ácido Tióctico/administração & dosagem , Aumento de Peso/efeitos dos fármacos , Adulto , Antioxidantes/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Gordura Intra-Abdominal/efeitos dos fármacos , Gordura Intra-Abdominal/fisiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Efeito Placebo , Fatores de Tempo , Resultado do Tratamento , Aumento de Peso/fisiologia
14.
IEEE Trans Vis Comput Graph ; 22(1): 519-28, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26390488

RESUMO

In this paper we move beyond memorability and investigate how visualizations are recognized and recalled. For this study we labeled a dataset of 393 visualizations and analyzed the eye movements of 33 participants as well as thousands of participant-generated text descriptions of the visualizations. This allowed us to determine what components of a visualization attract people's attention, and what information is encoded into memory. Our findings quantitatively support many conventional qualitative design guidelines, including that (1) titles and supporting text should convey the message of a visualization, (2) if used appropriately, pictograms do not interfere with understanding and can improve recognition, and (3) redundancy helps effectively communicate the message. Importantly, we show that visualizations memorable "at-a-glance" are also capable of effectively conveying the message of the visualization. Thus, a memorable visualization is often also an effective one.


Assuntos
Gráficos por Computador , Movimentos Oculares/fisiologia , Rememoração Mental/fisiologia , Percepção Visual/fisiologia , Adulto , Feminino , Humanos , Masculino , Análise e Desempenho de Tarefas , Adulto Jovem
15.
Int Immunopharmacol ; 5(5): 929-36, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15778128

RESUMO

This paper investigates how BST204, a fermented ginseng extract, affects the expression and mechanism of cyclooxygenase-2 (COX-2). BST204 was prepared by incubating crude ginseng extract with ginsenoside-beta-glucosidase. Unexpectedly, BST204 had no effect on the level of COX-2 protein in unstimulated RAW 264.7 cells, and it suppressed the level of COX-2 protein and PGE(2) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. It did not show any suppressive effect, though, on the COX-2 mRNA level. To investigate the suppressive mechanism of COX-2 protein, the activating phosphorylation of p70 S6 kinase and 4E-BP1, which are important for translation, were measured. The phosphorylation of p70 S6 kinase, not 4E-BP1, was increased by LPS in a time-dependent manner, and was inhibited by BST204 in a dose-dependent manner. The expression of COX-2 protein, however, was partially suppressed by rapamycin, an upstream inhibitor of p70 S6 kinase. Therefore, this paper suggests that the suppression of COX-2 protein by BST204 was partially correlated with the inhibition of p70 S6 kinase activation.


Assuntos
Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Panax , Prostaglandina-Endoperóxido Sintases/genética , Prostaglandina-Endoperóxido Sintases/metabolismo , Animais , Sequência de Bases , Linhagem Celular , Ciclo-Oxigenase 2 , DNA Complementar/genética , Ativação Enzimática/efeitos dos fármacos , Fermentação , Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/farmacologia , Camundongos , Panax/química , Extratos Vegetais/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Sirolimo/farmacologia
16.
J Pharm Pharmacol ; 57(7): 911-8, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15969952

RESUMO

In this study, the effects of BST204, a fermented ginseng extract, on the expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production are looked into. Crude ginseng extract was incubated with ginsenoside-beta-glucosidase to prepare BST204. BST204, unlike lipopolysaccharide (LPS) and crude ginseng extract, did not affect the level of iNOS protein and NO production in unstimulated RAW 264.7 cells. However, it suppressed the level of iNOS protein and NO production in LPS-stimulated RAW 264.7 cells but did not manifest the same effect on the iNOS mRNA level. An investigation of the activating phosphorylation of p70 S6 kinase and 4E-BP1, which are important for translation, was conducted to investigate the suppressive mechanism of iNOS protein. LPS increased the phosphorylation of p70 S6 kinase, but not 4E-BP1, in a time-dependent manner, and BST204 inhibited it in a dose-dependent manner. The expression of iNOS protein, however, was partially suppressed by rapamycin, an upstream inhibitor of p70 S6 kinase. Therefore, this paper suggests that the suppression of iNOS protein by BST204 was partially correlated with the inhibition of p70 S6 kinase activation.


Assuntos
Óxido Nítrico Sintase/biossíntese , Óxido Nítrico/biossíntese , Panax/química , Extratos Vegetais/farmacologia , Animais , Técnicas de Cultura de Células , Fermentação , Lipopolissacarídeos/farmacologia , Macrófagos , Camundongos , Óxido Nítrico Sintase Tipo II , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo
17.
Brain Res ; 1246: 136-43, 2008 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-18951885

RESUMO

The neural basis of ambivalence has not yet been identified. We investigated the prefrontal cortical activations implicated in evaluative processing of ambivalent stimuli under the forced and non-forced response conditions. Cerebral blood flow was measured using H(2)(15)O positron emission tomography in twelve normal volunteers during a modified word-stem completion task that was designed to evoke different conditions of ambivalence. The prefrontal cortical activations were restricted to the orbitofrontal cortex during the non-forced ambivalent condition, whereas the ventrolateral prefrontal cortex and the frontopolar cortex were activated in addition to the orbitofrontal cortex during the forced ambivalent condition. It is remarkable that the orbitofrontal cortex and the ventrolateral prefrontal cortex demonstrated a reciprocal activation pattern, which might be linked to the evaluative attitude toward the ambivalent stimuli.


Assuntos
Emoções , Lobo Frontal/fisiologia , Córtex Pré-Frontal/fisiologia , Adulto , Feminino , Lobo Frontal/diagnóstico por imagem , Humanos , Masculino , Modelos Estatísticos , Percepção , Tomografia por Emissão de Pósitrons , Córtex Pré-Frontal/diagnóstico por imagem , Leitura , Semântica , Adulto Jovem
18.
Toxicol Appl Pharmacol ; 220(3): 227-34, 2007 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-17395225

RESUMO

The anti-allergic action of various Oriental medicinal herbs was investigated using in vitro and in vivo experimental models. Of these extracts, the ethanol extract of Meliae cortex (MC) exhibited the most potent activity in mast cells; its IC(50) values were 29+/-1.5 microg/ml for antigen stimulation and 57+/-3.4 microg/ml for thapsigargin stimulation. It inhibited compound-48/80-induced systemic anaphylaxis by 52.9% at a dose of 300 mg/kg in mice; it also inhibited the expression of the proinflammatory mediator TNF-alpha. With regard to its mechanism of action, MC suppressed the activating phosphorylation of Syk, a key enzyme in mast-cell signaling processes and that of Akt in a dose-dependent manner. It also inhibited the MAP kinase ERK1/2, which is critical for the production of inflammatory cytokines in mast cells, as indicated by the suppression of the activating phosphorylation of ERK1/2. Taken together, these results suggest that the anti-allergic activity of MC may be due to the inhibition of histamine secretion and cytokine expression through the Syk inhibition in mast cells.


Assuntos
Antialérgicos/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Mastócitos/efeitos dos fármacos , Melia azedarach/química , Proteínas Tirosina Quinases/antagonistas & inibidores , Anafilaxia/induzido quimicamente , Anafilaxia/fisiopatologia , Anafilaxia/prevenção & controle , Animais , Antialérgicos/química , Degranulação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Immunoblotting , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Mastócitos/enzimologia , Mastócitos/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteínas Tirosina Quinases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Quinase Syk , Tapsigargina/toxicidade , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , p-Metoxi-N-metilfenetilamina/toxicidade
19.
Blood ; 108(3): 956-64, 2006 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-16861349

RESUMO

Mast cells are responsible for IgE-mediated allergic reactions. Phospholipase D1 (PLD1) and PLD2 regulate mast cell activation, but the mechanisms remain unclear. Here we show that PLD2 associates with and promotes activation of Syk, a key enzyme in mast cell activation. Antigen stimulation resulted in increased association and colocalization of Syk with PLD2 on the plasma membrane as indicated by coimmunoprecipitation and confocal microscopy. This association was dependent on tyrosine phosphorylation of Syk but not on PLD2 activity. In vitro, PLD2 interacted via its Phox homology (PX) domain with recombinant Syk to induce phosphorylation and activation of Syk. Furthermore, overexpression of PLD2 or catalytically inactive PLD2K758R enhanced antigen-induced phosphorylations of Syk and its downstream targets, the adaptor proteins LAT and SLP-76, while expression of a PLD2 siRNA blocked these phosphorylations. Apparently, the interaction of PLD2 with Syk is an early critical event in the activation of mast cells.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Mastócitos/metabolismo , Fosfolipase D/metabolismo , Proteínas Tirosina Quinases/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Animais , Antígenos/fisiologia , Sítios de Ligação , Degranulação Celular , Linhagem Celular , Mastócitos/enzimologia , Mastócitos/imunologia , Fosfolipase D/fisiologia , Fosforilação , Ligação Proteica , Ratos , Quinase Syk , Transfecção
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