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1.
PLoS One ; 19(4): e0302022, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635538

RESUMO

BACKGROUND: The conventional methods and strategies used for knowledge translation (KT) in academic research often fall short in effectively reaching stakeholders, such as citizens, practitioners, and decision makers, especially concerning complex healthcare issues. In response, a growing number of scholars have been embracing arts-based knowledge translation (ABKT) to target a more diverse audience with varying backgrounds and expectations. Despite the increased interest, utilization, and literature on arts-based knowledge translation over the past three decades, no studies have directly compared traditional knowledge translation with arts-based knowledge translation methods. Thus, our study aimed to evaluate and compare the impact of an arts-based knowledge translation intervention-a circus show-with two traditional knowledge translation interventions (webinar and research report) in terms of awareness, accessibility, engagement, advocacy/policy influence, and enjoyment. METHODS: To conduct this exploratory convergent mixed method study, we randomly assigned 162 participants to one of the three interventions. All three knowledge translation methods were used to translate the same research project: "Rural Emergency 360: Mobilization of decision-makers, healthcare professionals, patients, and citizens to improve healthcare and services in Quebec's rural emergency departments (UR360)." RESULTS: The findings revealed that the circus show outperformed the webinar and research report in terms of accessibility and enjoyment, while being equally effective in raising awareness, increasing engagement, and influencing advocacy/policy. Each intervention strategy demonstrates its unique array of strengths and weaknesses, with the circus show catering to a diverse audience, while the webinar and research report target more informed participants. These outcomes underscore the innovative and inclusive attributes of Arts-Based Knowledge translation, showcasing its capacity to facilitate researchers' engagement with a wider array of stakeholders across diverse contexts. CONCLUSION: As a relevant first step and a complementary asset, arts-based knowledge translation holds immense potential in increasing awareness and mobilization around crucial health issues.


Assuntos
Atenção à Saúde , Ciência Translacional Biomédica , Humanos , Quebeque , Canadá , Serviço Hospitalar de Emergência
2.
NPJ Biofilms Microbiomes ; 10(1): 18, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448452

RESUMO

Cranberry is associated with multiple health benefits, which are mostly attributed to its high content of (poly)phenols, particularly flavan-3-ols. However, clinical trials attempting to demonstrate these positive effects have yielded heterogeneous results, partly due to the high inter-individual variability associated with gut microbiota interaction with these molecules. In fact, several studies have demonstrated the ability of these molecules to modulate the gut microbiota in animal and in vitro models, but there is a scarcity of information in human subjects. In addition, it has been recently reported that cranberry also contains high concentrations of oligosaccharides, which could contribute to its bioactivity. Hence, the aim of this study was to fully characterize the (poly)phenolic and oligosaccharidic contents of a commercially available cranberry extract and evaluate its capacity to positively modulate the gut microbiota of 28 human subjects. After only four days, the (poly)phenols and oligosaccharides-rich cranberry extract, induced a strong bifidogenic effect, along with an increase in the abundance of several butyrate-producing bacteria, such as Clostridium and Anaerobutyricum. Plasmatic and fecal short-chain fatty acids profiles were also altered by the cranberry extract with a decrease in acetate ratio and an increase in butyrate ratio. Finally, to characterize the inter-individual variability, we stratified the participants according to the alterations observed in the fecal microbiota following supplementation. Interestingly, individuals having a microbiota characterized by the presence of Prevotella benefited from an increase in Faecalibacterium with the cranberry extract supplementation.


Assuntos
Microbioma Gastrointestinal , Vaccinium macrocarpon , Animais , Humanos , Butiratos , Fenóis , Extratos Vegetais/farmacologia , Oligossacarídeos , Suplementos Nutricionais
3.
Front Sports Act Living ; 5: 1273327, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38033653

RESUMO

Introduction: The golden section or golden ratio (61.8% or 0.618) is a mathematical phenomenon that appears in art, literature, music and nature with such ubiquity that it is thought to be a fundamental principle of aesthetic organisation. The golden ratio also manifests in sport, particularly as the proportion of wins to losses required to win a Major League Baseball championship. This study extends early work on the golden ratio in baseball by incorporating more than three decades of additional data. Methods: This study involved a historically contextualized examination of how winning percentages have changed across the seven historical eras of modern baseball, including analyses of the relative contribution of offensive and defensive statistics to championship winning teams. Data was extracted from Baseball Reference and included statistics for 398 championship winning teams from both the American and National Leagues between 1901 and 2019. Pearson correlation coefficients were computed for winning percentage with indicators of offensive and defensive performance during each era. Main and interaction effects of Era and League on winning percentage were examined using factorial ANOVA, with follow-up analyses examining whether the golden ratio was included in each factor's 95% confidence interval. Results: Our findings suggest that winning percentages for championship teams were closest to the golden ratio during eras where the relative contribution of offense and defense was most closely balanced: the Integration Era (1942-1960) and the Expansion Era (1961-1976). Discussion: Previous scholarship theorizes that the golden ratio represents an aesthetic ideal or a Gestalt archetype. If this aesthetic theory is applied to sporting competition, these results suggest that baseball may be most aesthetically appealing to fans when offense and defense is balanced in such a way as to ensure that championship teams win 61.8% of their games.

4.
Front Psychol ; 14: 1089264, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36935971

RESUMO

This conceptual analysis aims to challenge the state of high-performance sport by questioning the concept of specialization. To start, we offer a brief, but critical overview of what specialization currently entails. Then, shifting the paradigm, we suggest an expansion rather than a reduction of developmental possibilities once an athlete reaches the "top". Specifically, rather than athletes conforming to national standards imposed by governing bodies about what it means to be "elite", we suggest sport systems consider a person-environment fit approach to support ongoing development. Drawing on an ecological dynamics rationale and various socio-cultural theories, we explore how concepts such as affordances and perspectives can be harnessed to create a better "fit" between athletes' action capabilities and the opportunities within their broader environment. Our conception of specialization requires moving away from a definition of success based on the accumulation of medals, toward one that accounts for the exploration and achievement of the possible. We argue that a person-environment fit welcomes diversity, so long as it sustains the person's health, wellbeing, and performance. This, it is suggested, is about collectively holding open spaces for each other to explore beyond the constraints of high-performance sport, encouraging all to carry on their lives in directions meaningfully impactful for them. We conclude this conceptual analysis with a brief case example demonstrating what our theorizing could look like in practice.

5.
Breastfeed Med ; 18(1): 14-22, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36409543

RESUMO

Background: Gestational diabetes mellitus (GDM) is known to affect human milk composition. Aims of this study were to compare macronutrient and energy content of human milk of women with (GDM+) and without GDM (GDM-), to assess the association between maternal health and human milk macronutrient and energy content and association between human milk macronutrient and energy content and infant growth. Study Design and Methods: Two months after delivery, hindmilk samples were collected. Triglyceride (TG), lactose, and protein content of human milk were measured. An oral glucose tolerance test was performed. Infant weight and length at birth and 2 months were collected. Weight-for-age (WAZ) and weight-for-length z-scores were calculated. Results: Twenty-four GDM+ and 29 GDM- women were included. Protein, lactose, and energy content of human milk were similar between groups. TG concentration was higher in GDM+ than in GDM- women (6.3 ± 2.0 versus 5.3 ± 1.2, p = 0.04). This difference was no longer significant after adjustment for maternal age and infant sex (p = 0.23). Maternal age was associated with TG (r = 0.28, p = 0.04) and lactose (r = -0.30, p = 0.03), while fasting glucose was associated with proteins (r = 0.30, p = 0.03) and tended to be associated with TG (r = 0.27, p = 0.05) and energy (r = 0.24, p = 0.08). TG levels in human milk were associated with weight (ß: 0.26, 95% confidence interval [CI]: 0.02 to 0.50) and WAZ (ß: 0.40, 95% CI: 0.05 to 0.75) at 2 months among children unexposed (GDM-) to GDM, but not among children exposed (GDM+) Conclusions: In conclusion, GDM status, maternal age, and fasting glucose level were associated with human milk composition. Finally, TG in human milk was associated with infant growth among GDM- children but not among GDM+ children. ClinicalTrials.gov NCT02872402.


Assuntos
Diabetes Gestacional , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Aleitamento Materno , Diabetes Gestacional/metabolismo , Glucose , Lactose , Leite Humano/metabolismo
6.
Med Probl Perform Art ; 37(4): 249-258, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36455109

RESUMO

OBJECTIVE: The circus professionalization process entails extensive training to mitigate the high-risk demands which increase stress in artists. In high-risk professions, everyday hassles (challenges) contribute greatly to overall stress. To capture the impact of daily challenges on student-artists, the aim of the current study was to describe the magnitude and pattern of daily challenges as well as their relationships with perceived coping, anxiety, fatigue, and psychological distress. METHODS: Ninety-two students at École Nationale de Cirque (ENC), in Montreal, Canada, completed the Circus Daily Challenges Questionnaire (CDCQ) and scales assessing perceived coping, state anxiety, and fatigue at four time points over 1 school year. The Kessler 6 Non-Specific Psychological Distress Scale (K6) was implemented at one time point. RESULTS: Findings revealed significant fluctuations in challenge level and management of challenges throughout the school year, with schedule, technical development, artistic expression, physical preparation, and sleep reported as high during the two examination periods. The lowest challenge-level scores were achieved following the extended breaks in the annual calendar. Daily challenge positively correlated to state anxiety and fatigue, and negatively correlated with perceived coping. The student-artists reported higher prevalence of moderate psychological distress to general populations. CONCLUSION: Befitting the Stress Process Model, a strong interplay between variables was observed, and the life challenges assessment provides a basis for interventions based upon commonalities across the group, as well as individually tailored.


Assuntos
Instituições Acadêmicas , Estudantes , Humanos , Estudos Longitudinais , Ansiedade/epidemiologia , Fadiga
7.
Int J Sports Phys Ther ; 17(2): 307-316, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35136700

RESUMO

Medical management of the circus performer encompasses a wide variety of multicultural, transdisciplinary and multifaceted decision-making considerations. There is a paucity of research evidence investigating both the unique diversity of skill sets and cultural considerations in addition to injury patterns of performers within the circus environment. Since a previously established framework for supporting the health and well-being of the circus performer across various aspects of medical management does not exist in the literature, most recommendations in this regard must come from practical experience working with this highly specialized performance athlete population. The purpose of this clinical commentary is to provide the reader with a greater understanding of the unique challenges associated with the medical management of performance artists and acrobats as well as recommendations for developing an integrated approach for mitigating injury risk within a highly specialized, diverse athlete population. LEVEL OF EVIDENCE: 5.

8.
Front Psychol ; 12: 690710, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659006

RESUMO

In a global and highly competitive world, the importance of creativity is increasing as it supports adaptability, health, and actualization. Yet, because most research focuses on what it takes to produce creative artifacts, interventions supporting growth in creative potential remains underexplored. To address this limitation, the first goal of this paper is to review the creativity science literature to identify the elements that underpin the realization of an individual's creative potential. The summary of the literature is presented using a framework which highlights the interactions between environmental elements (i.e., cultural values, social interactions, and material world) and actors' elements (i.e., affective attributes and states, cognitive skills, and physical expression). Using a systemic perspective, the framework illustrates 'what' creativity enhancement interventions should aim for, to facilitate the emergence of creative actions. Given the current lack of holistic, embodied, and interactive evidence-based interventions to nurture the creative potential elements identified, the second part of this review builds on movement sciences literature and physical literacy conceptualization to suggest that enriched movement activities are promising avenues to explore. Specifically, following non-linear pedagogy approaches, an intervention called movement improvisation is introduced. Ecological dynamics principles are used to explain how improvising with movement in a risk-friendly environment can lead to cognitive, affective, social, and cultural repertoire expansion. To interrogate this argument further, the review concludes with possible solutions to withstand research challenges and raises future study questions. Overall, combining creativity and movement sciences in this review demonstrates the potential for well-designed movement interventions to ignite creative potential for individuals and overcome the tendency to remain anchored in a state of inertia.

9.
Front Psychol ; 12: 577882, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613376

RESUMO

The COVID-19 pandemic resulted in the abrupt closure of circus schools, venues, and companies, introducing a myriad of novel stressors. Performers and students must now attempt to maintain their technical, physical, artistic, creative, and cognitive abilities without in-person support from their coaches and must manage the isolation from their training and performing spaces. For circus artists, the transposition of the work space to a home environment is not possible, which creates novel stressors that could lead to the exacerbation and escalation of mental health issues. The purpose of this study is to develop, implement and evaluate a holistic interventional program based on the socio-ecological model of resilience and operationalized through physical literacy. This will be a prospective longitudinal study with a retrospective comparison to data from a similar student cohort pre-pandemic. Interventions were designed using a population-specific, participant-based developmental model within a knowledge translation framework. The interventional program includes group webinars, small group information sessions, and one-on-one Zoom meetings, in addition to the distribution of electronic educational materials. The interventions will holistically provide psychological, physical, social, technical, artistic, and creative supports. Resources will be deployed throughout the closure period and through recovery, as transitions to return to training after prolonged hiatus will magnify known psychological and physical difficulties. Repeated, longitudinal assessment of students will be utilized to track changes over time at key transitions in the pandemic and school year and will be compared to a pre-pandemic school year. The framework for this program will be translatable to other performing arts and high-performance contexts. The program has implications for the mental health and overall wellbeing of artists and for cultural and economic recovery of the industry.

10.
Foods ; 2(4): 444-459, 2013 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-28239128

RESUMO

The objective of this study was to assess the impact of using heat-denatured whey:buttermilk protein aggregate in acid-set type yogurt production. Whey and buttermilk (25:75) protein concentrate was adjusted to pH 4.6, heated at 90 °C for 5 min, homogenized and freeze-dried. Set-type yogurts were prepared from skim milk standardized to 15% (w/v) total solids and 4.2% (w/v) protein using different levels of powdered skim milk or freeze-dried protein aggregate. The use of the protein aggregate significantly modified yogurt texture, but did not affect the water-holding capacity of the gel. Confocal laser-scanning microscope images showed the presence of large particles in milk enriched with protein aggregate, which directly affected the homogeneity of the clusters within the protein matrix. Thiol groups were freed during heating of the protein aggregate suspended in water, suggesting that the aggregates could interact with milk proteins during heating.

11.
PLoS Pathog ; 7(2): e1001286, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21379336

RESUMO

Apicomplexan parasites cause devastating diseases including malaria and toxoplasmosis. They harbour a plastid-like, non-photosynthetic organelle of algal origin, the apicoplast, which fulfils critical functions for parasite survival. Because of its essential and original metabolic pathways, the apicoplast has become a target for the development of new anti-apicomplexan drugs. Here we show that the lipid phosphatidylinositol 3-monophosphate (PI3P) is involved in apicoplast biogenesis in Toxoplasma gondii. In yeast and mammalian cells, PI3P is concentrated on early endosomes and regulates trafficking of endosomal compartments. Imaging of PI3P in T. gondii showed that the lipid was associated with the apicoplast and apicoplast protein-shuttling vesicles. Interference with regular PI3P function by over-expression of a PI3P specific binding module in the parasite led to the accumulation of vesicles containing apicoplast peripheral membrane proteins around the apicoplast and, ultimately, to the loss of the organelle. Accordingly, inhibition of the PI3P-synthesising kinase interfered with apicoplast biogenesis. These findings point to an unexpected implication for this ubiquitous lipid and open new perspectives on how nuclear encoded proteins traffic to the apicoplast. This study also highlights the possibility of developing specific pharmacological inhibitors of the parasite PI3-kinase as novel anti-apicomplexan drugs.


Assuntos
Organelas/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Toxoplasma/crescimento & desenvolvimento , Toxoplasma/metabolismo , Toxoplasmose/metabolismo , Animais , Animais Geneticamente Modificados , Apicomplexa , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibroblastos/parasitologia , Prepúcio do Pênis/citologia , Prepúcio do Pênis/metabolismo , Prepúcio do Pênis/parasitologia , Proteínas de Fluorescência Verde/genética , Humanos , Masculino , Biogênese de Organelas , Organelas/parasitologia , Fosfatidilinositol 3-Quinases/metabolismo , Toxoplasma/patogenicidade , Toxoplasmose/parasitologia
12.
Eukaryot Cell ; 9(10): 1519-30, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20709789

RESUMO

Phosphoinositides are important regulators of diverse cellular functions, and phosphatidylinositol 3-monophosphate (PI3P) is a key element in vesicular trafficking processes. During its intraerythrocytic development, the malaria parasite Plasmodium falciparum establishes a sophisticated but poorly characterized protein and lipid trafficking system. Here we established the detailed phosphoinositide profile of P. falciparum-infected erythrocytes and found abundant amounts of PI3P, while phosphatidylinositol 3,5-bisphosphate was not detected. PI3P production was parasite dependent, sensitive to a phosphatidylinositol-3-kinase (PI3-kinase) inhibitor, and predominant in late parasite stages. The Plasmodium genome encodes a class III PI3-kinase of unusual size, containing large insertions and several repetitive sequence motifs. The gene could not be deleted in Plasmodium berghei, and in vitro growth of P. falciparum was sensitive to a PI3-kinase inhibitor, indicating that PI3-kinase is essential in Plasmodium blood stages. For intraparasitic PI3P localization, transgenic P. falciparum that expressed a PI3P-specific fluorescent probe was generated. Fluorescence was associated mainly with the membrane of the food vacuole and with the apicoplast, a four-membrane bounded plastid-like organelle derived from an ancestral secondary endosymbiosis event. Electron microscopy analysis confirmed these findings and revealed, in addition, the presence of PI3P-positive single-membrane vesicles. We hypothesize that these vesicles might be involved in transport processes, likely of proteins and lipids, toward the essential and peculiar parasite compartment, which is the apicoplast. The fact that PI3P metabolism and function in Plasmodium appear to be substantially different from those in its human host could offer new possibilities for antimalarial chemotherapy.


Assuntos
Eritrócitos/parasitologia , Fosfatos de Fosfatidilinositol/metabolismo , Plasmodium falciparum/enzimologia , Plastídeos/metabolismo , Vacúolos/metabolismo , Animais , Corantes Fluorescentes , Humanos , Microscopia de Fluorescência , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Plasmodium berghei , Plasmodium falciparum/genética , Plasmodium falciparum/metabolismo , Plasmodium falciparum/fisiologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Transfecção
13.
J Cell Biol ; 182(3): 603-14, 2008 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-18695048

RESUMO

Spatial regulation is an important feature of signal specificity elicited by cytoplasmic tyrosine kinases of the Src family (SRC family protein tyrosine kinases [SFK]). Cholesterol-enriched membrane domains, such as caveolae, regulate association of SFK with the platelet-derived growth factor receptor (PDGFR), which is needed for kinase activation and mitogenic signaling. PAG, a ubiquitously expressed member of the transmembrane adaptor protein family, is known to negatively regulate SFK signaling though binding to Csk. We report that PAG modulates PDGFR levels in caveolae and SFK mitogenic signaling through a Csk-independent mechanism. Regulation of SFK mitogenic activity by PAG requires the first N-terminal 97 aa (PAG-N), which include the extracellular and transmembrane domains, palmitoylation sites, and a short cytoplasmic sequence. We also show that PAG-N increases ganglioside GM1 levels at the cell surface and, thus, displaces PDGFR from caveolae, a process that requires the ganglioside-specific sialidase Neu-3. In conclusion, PAG regulates PDGFR membrane partitioning and SFK mitogenic signaling by modulating GM1 levels within caveolae independently from Csk.


Assuntos
Gangliosídeo G(M1)/metabolismo , Proteínas de Membrana/metabolismo , Mitógenos/metabolismo , Fosfoproteínas/metabolismo , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Proteína Tirosina Quinase CSK , Cavéolas/efeitos dos fármacos , Cavéolas/ultraestrutura , DNA/biossíntese , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Proteínas de Membrana/química , Camundongos , Modelos Biológicos , Células NIH 3T3 , Neuraminidase/metabolismo , Fosfoproteínas/química , Ligação Proteica/efeitos dos fármacos , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Quinases da Família src
14.
Dis Aquat Organ ; 58(1): 83-7, 2004 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-15038456

RESUMO

The availability of specific and reliable detection methods is essential for monitoring the health status of farmed species, particularly for viral diseases. Extra small virus (XSV), a virus-like particle, is associated with Macrobrachium rosenbergii Noda virus (MrNV) in white tail disease (WTD) of M. rosenbergii. We developed 2 genome-based detection methods for the identification of XSV, namely dot-blot hybridization and a single-step RT-PCR. Detection limits were established and are ca. 2.5 pg and 5 fg of viral RNA for dot-blot hybridization and RT-PCR, respectively. Application of the methods to field samples indicated that some animals positively diagnosed with MrNV did not contain XSV, at least within the detection limit of the methodology. This raises the question of the actual role of XSV and its interactions with MrNV in WTD of M. rosenbergii.


Assuntos
Nodaviridae , Palaemonidae/virologia , RNA Viral/genética , Animais , Aquicultura , Primers do DNA , Sondas de DNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
Eur J Biochem ; 270(13): 2805-13, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12823551

RESUMO

To elucidate the structural features of the mussel defensin MGD1 required for antimicrobial activity, we synthesized a series of peptides corresponding to the main known secondary structures of the molecule and evaluated their activity towards Gram-positive and Gram-negative bacteria, and filamentous fungi. We found that the nonapeptide corresponding to residues 25-33 of MGD1 (CGGWHRLRC) exhibited bacteriostatic activity once it was cyclized by a non-naturally occurring disulfide bridge. Longer peptides corresponding to the amino acid sequences of the alpha-helical part or to the beta-strands of MGD1 had no detectable activity. The bacteriostatic activity of the sequence 25-33 was strictly dependent on the bridging of Cys25 and Cys33 and was proportional to the theoretical isoelectric point of the peptide, as deduced from the variation of activity in a set of peptide analogues of the 25-33 sequence with different numbers of cationic charges. By using confocal fluorescence microscopy, we found that the cyclic peptides bound to Gram-positive bacteria without apparent lysis. However, by using a fluorescent dye, we observed that dead bacteria had been permeated by the cyclic peptide 25-33. Sequence comparisons in the family of arthopod defensins indicate that MGD1 belongs to a subfamily of the insect defensins, characterized by the constant occurrence of both positively charged and hydrophobic amino acids in the loop. Modelling studies showed that in the MGD1 structure, positively charged and hydrophobic residues are organized in two layered clusters, which might have a functional significance in the docking of MGD1 to the bacterial membrane.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/metabolismo , Defensinas , Estrutura Terciária de Proteína , Proteínas/química , Proteínas/metabolismo , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Bactérias/metabolismo , Bivalves/química , Fusarium/metabolismo , Ponto Isoelétrico , Testes de Sensibilidade Microbiana , Modelos Moleculares , Dados de Sequência Molecular , Família Multigênica , Ligação Proteica , Proteínas/genética , Alinhamento de Sequência
16.
Oncogene ; 22(12): 1836-47, 2003 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-12660819

RESUMO

Cellular stress activates multiple mitogen-activated protein kinase (MAPK) cascades and immediate-early gene (IEG) transcription. To address how these events are linked, we investigated the endogenous signaling/transcription factor network driving IEG activation by arsenite and anisomycin in the human osteosarcoma cell line HOS/TE-85. Induction of IEG transcription by both stresses corresponded temporally with the phosphorylation of the regulatory factors Elk-1 and cAMP response element-binding protein (CREB), along with activation of the extracellular signal-regulated kinase (ERK), stress-activated protein kinase (SAPK) and p38 MAPK cascades. To assess the role of the different cascades, they were selectively inhibited with PD98059, SP600125 and SB203580, respectively. This implicated all three cascades in Elk-1 phosphorylation after arsenite treatment, whereas ERK and SAPK inhibition diminished this, and IEG mRNA levels, downstream of anisomycin. SB blocked phosphorylation of both serum response factor (SRF) and CREB, and strongly reduced IEG activation by both stresses. Combining PD with SB further reduced arsenite induction of IEG transcription. Thus, all three MAPK cascades mediate anisomycin- and arsenite-induced signaling to IEG promoters in HOS cells through the differential targeting of Elk-1, SRF and CREB.


Assuntos
Anisomicina/farmacologia , Arsenitos/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas de Ligação a DNA , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes Precoces , Sistema de Sinalização das MAP Quinases , Proteínas Proto-Oncogênicas/metabolismo , Fator de Resposta Sérica/metabolismo , Fatores de Transcrição , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Fosforilação , Ativação Transcricional , Células Tumorais Cultivadas , Proteínas Elk-1 do Domínio ets
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