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DSIF, the Paf1 complex, and Tat-SF1 have nonredundant, cooperative roles in RNA polymerase II elongation

Chen, Yexi; Yamaguchi, Yuki; Tsugeno, Yuta; Yamamoto, Junichi; Yamada, Tomoko; Nakamura, Mitsuhiro; Hisatake, Koji; Handa, Hiroshi
Fonte: Cold Spring Harbor Laboratory Press Publicador: Cold Spring Harbor Laboratory Press
Tipo: Artigo de Revista Científica
Publicado em 01/12/2009 EN
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46.06%
Transcription elongation factor DSIF/Spt4–Spt5 is capable of promoting and inhibiting RNA polymerase II elongation and is involved in the expression of various genes. While it has been known for many years that DSIF inhibits elongation in collaboration with the negative elongation factor NELF, how DSIF promotes elongation is largely unknown. Here, an activity-based biochemical approach was taken to understand the mechanism of elongation activation by DSIF. We show that the Paf1 complex (Paf1C) and Tat-SF1, two factors implicated previously in elongation control, collaborate with DSIF to facilitate efficient elongation. In human cells, these factors are recruited to the FOS gene in a temporally coordinated manner and contribute to its high-level expression. We also show that elongation activation by these factors depends on P-TEFb-mediated phosphorylation of the Spt5 C-terminal region. A clear conclusion emerging from this study is that a set of elongation factors plays nonredundant, cooperative roles in elongation. This study also shows unambiguously that Paf1C, which is generally thought to have chromatin-related functions, is involve directlyd in elongation control.

Cooperative Interactions between TLR4 and TLR9 Regulate Interleukin 23 and 17 Production in a Murine Model of Gram Negative Bacterial Pneumonia

Bhan, Urvashi; Ballinger, Megan N.; Zeng, Xianying; Newstead, Michael J.; Cornicelli, Matthew D.; Standiford, Theodore J.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 26/03/2010 EN
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36.02%
Toll like receptors play an important role in lung host defense against bacterial pathogens. In this study, we investigated independent and cooperative functions of TLR4 and TLR9 in microbial clearance and systemic dissemination during Gram-negative bacterial pneumonia. To access these responses, wildtype Balb/c mice, mice with defective TLR4 signaling (TLR4lps-d), mice deficient in TLR9 (TLR9−/−) and TLR4/9 double mutant mice (TLR4lps-d/TLR9−/−) were challenged with K. pneumoniae, then time-dependent lung bacterial clearance and systemic dissemination determined. We found impaired lung bacterial clearance in TLR4 and TLR9 single mutant mice, whereas the greatest impairment in clearance was observed in TLR4lps-d/TLR9−/− double mutant mice. Early lung expression of TNF-α, IL-12, and chemokines was TLR4 dependent, while IFN-γ production and the later expression of TNF-α and IL-12 was dependent on TLR9. Classical activation of lung macrophages and maximal induction of IL-23 and IL-17 required both TLR4 and TLR9. Finally, the i.t. instillation of IL-17 partially restored anti-bacterial immunity in TLR4lps-d/TLR9−/− double mutant mice. In conclusion, our studies indicate that TLR4 and TLR9 have both non-redundant and cooperative roles in lung innate responses during Gram-negative bacterial pneumonia and are both critical for IL-17 driven antibacterial host response.

Physiological Roles of Class I HDAC Complex and Histone Demethylase

Hayakawa, Tomohiro; Nakayama, Jun-ichi
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
EN
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35.96%
Epigenetic gene silencing is one of the fundamental mechanisms for ensuring proper gene expression patterns during cellular differentiation and development. Histone deacetylases (HDACs) are evolutionally conserved enzymes that remove acetyl modifications from histones and play a central role in epigenetic gene silencing. In cells, HDAC forms a multiprotein complex (HDAC complex) in which the associated proteins are believed to help HDAC carry out its cellular functions. Though each HDAC complex contains distinct components, the presence of isoforms for some of the components expands the variety of complexes and the diversity of their cellular roles. Recent studies have also revealed a functional link between HDAC complexes and specific histone demethylases. In this paper, we summarize the distinct and cooperative roles of four class I HDAC complexes, Sin3, NuRD, CoREST, and NCoR/SMRT, with respect to their component diversity and their relationship with specific histone demethylases.

Cooperative Roles of Fish Protein Kinase Containing Z-DNA Binding Domains and Double-Stranded RNA-Dependent Protein Kinase in Interferon-Mediated Antiviral Response▿†

Liu, Ting-Kai; Zhang, Yi-Bing; Liu, Ying; Sun, Fan; Gui, Jian-Fang
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /12/2011 EN
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35.94%
The double-stranded RNA (dsRNA)-dependent protein kinase (PKR) inhibits protein synthesis by phosphorylating eukaryotic translation initiation factor 2α (eIF2α). In fish species, in addition to PKR, there exists a PKR-like protein kinase containing Z-DNA binding domains (PKZ). However, the antiviral role of fish PKZ and the functional relationship between fish PKZ and PKR remain unknown. Here we confirmed the coexpression of fish PKZ and PKR proteins in Carassius auratus blastula embryonic (CAB) cells and identified them as two typical interferon (IFN)-inducible eIF2α kinases, both of which displayed an ability to inhibit virus replication. Strikingly, fish IFN or all kinds of IFN stimuli activated PKZ and PKR to phosphorylated eIF2α. Overexpression of both fish kinases together conferred much more significant inhibition of virus replication than overexpression of either protein, whereas morpholino knockdown of both made fish cells more vulnerable to virus infection than knockdown of either. The antiviral ability of fish PKZ was weaker than fish PKR, which correlated with its lower ability to phosphorylate eIF2α than PKR. Moreover, the independent association of fish PKZ or PKR reveals that each of them formed homodimers and that fish PKZ phosphorylated eIF2α independently on fish PKR and vice versa. These results suggest that fish PKZ and PKR play a nonredundant but cooperative role in IFN antiviral response.

The relative roles of fHbp, NspA and lipooligosaccharide sialylation in regulation of the alternative pathway of complement on meningococci

Lewis, Lisa A.; Carter, Matthew; Ram, Sanjay
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
36.06%
Neisseria meningitidis inhibits the alternative pathway (AP) of complement utilizing diverse mechanisms, including expression of capsule (select serogroups), Neisserial surface protein A (NspA), factor H binding protein (fHbp) and lipooligosaccharide (LOS) sialylation. The contribution of the latter three molecules in AP regulation in encapsulated meningococci was studied using isogenic mutants. When LOS was unsialylated, deleting NspA alone from group A strain A2594 (low fHbp/high NspA) significantly increased AP-mediated C3 deposition. C3 deposition further increased ~2-fold in a ΔfHbpΔNspA double mutant, indicating cooperative fHbp function. LOS sialylation of A2594 ΔfHbpΔNspA decreased the rate of C3 deposition, revealing AP inhibition by LOS sialic acid. Maximal C3 deposition on group B strain H44/76 (high fHbp/low NspA) occurred when all three molecules were absent; again, LOS sialylation attenuated the AP in the absence of both fHbp and NspA. When H44/76 LOS was unsialylated, both fHbp and NspA independently inhibited the AP. LOS sialylation enhanced binding of fH C-terminal domains 18–20 to C3 fragments deposited on bacteria. Interaction of meningococci with non-human complement is relevant for animal models and vaccine evaluation studies that employ non-human complement. Consistent with their human-specific fH binding...

In Vitro Assays Using Primary Embryonic Mouse Lymphatic Endothelial Cells Uncover Key Roles for FGFR1 Signalling in Lymphangiogenesis

Kazenwadel, Jan; Secker, Genevieve A.; Betterman, Kelly L.; Harvey, Natasha L.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 06/07/2012 EN
Relevância na Pesquisa
35.96%
Despite the importance of blood vessels and lymphatic vessels during development and disease, the signalling pathways underpinning vessel construction remain poorly characterised. Primary mouse endothelial cells have traditionally proven difficult to culture and as a consequence, few assays have been developed to dissect gene function and signal transduction pathways in these cells ex vivo. Having established methodology for the purification, short-term culture and transfection of primary blood (BEC) and lymphatic (LEC) vascular endothelial cells isolated from embryonic mouse skin, we sought to optimise robust assays able to measure embryonic LEC proliferation, migration and three-dimensional tube forming ability in vitro. In the course of developing these assays using the pro-lymphangiogenic growth factors FGF2 and VEGF-C, we identified previously unrecognised roles for FGFR1 signalling in lymphangiogenesis. The small molecule FGF receptor tyrosine kinase inhibitor SU5402, but not inhibitors of VEGFR-2 (SU5416) or VEGFR-3 (MAZ51), inhibited FGF2 mediated LEC proliferation, demonstrating that FGF2 promotes proliferation directly via FGF receptors and independently of VEGF receptors in primary embryonic LEC. Further investigation revealed that FGFR1 was by far the predominant FGF receptor expressed by primary embryonic LEC and correspondingly...

Dispensable, Redundant, Complementary, and Cooperative Roles of Dopamine, Octopamine, and Serotonin in Drosophila melanogaster

Chen, Audrey; Ng, Fanny; Lebestky, Tim; Grygoruk, Anna; Djapri, Christine; Lawal, Hakeem O.; Zaveri, Harshul A.; Mehanzel, Filmon; Najibi, Rod; Seidman, Gabriel; Murphy, Niall P.; Kelly, Rachel L.; Ackerson, Larry C.; Maidment, Nigel T.; Jackson, F. Rob;
Fonte: Genetics Society of America Publicador: Genetics Society of America
Tipo: Artigo de Revista Científica
Publicado em /01/2013 EN
Relevância na Pesquisa
35.94%
To investigate the regulation of Drosophila melanogaster behavior by biogenic amines, we have exploited the broad requirement of the vesicular monoamine transporter (VMAT) for the vesicular storage and exocytotic release of all monoamine neurotransmitters. We used the Drosophila VMAT (dVMAT) null mutant to globally ablate exocytotic amine release and then restored DVMAT activity in either individual or multiple aminergic systems, using transgenic rescue techniques. We find that larval survival, larval locomotion, and female fertility rely predominantly on octopaminergic circuits with little apparent input from the vesicular release of serotonin or dopamine. In contrast, male courtship and fertility can be rescued by expressing DVMAT in octopaminergic or dopaminergic neurons, suggesting potentially redundant circuits. Rescue of major aspects of adult locomotion and startle behavior required octopamine, but a complementary role was observed for serotonin. Interestingly, adult circadian behavior could not be rescued by expression of DVMAT in a single subtype of aminergic neurons, but required at least two systems, suggesting the possibility of unexpected cooperative interactions. Further experiments using this model will help determine how multiple aminergic systems may contribute to the regulation of other behaviors. Our data also highlight potential differences between behaviors regulated by standard exocytotic release and those regulated by other mechanisms.

Cooperative Roles of SDF-1α and EGF Gradients on Tumor Cell Migration Revealed by a Robust 3D Microfluidic Model

Kim, Beum Jun; Hannanta-anan, Pimkhuan; Chau, Michelle; Kim, Yoon Soo; Swartz, Melody A.; Wu, Mingming
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 15/07/2013 EN
Relevância na Pesquisa
46.06%
Chemokine-mediated directed tumor cell migration within a three dimensional (3D) matrix, or chemoinvasion, is an important early step in cancer metastasis. Despite its clinical importance, it is largely unknown how cytokine and growth factor gradients within the tumor microenvironment regulate chemoinvasion. We studied tumor cell chemoinvasion in well-defined and stable chemical gradients using a robust 3D microfluidic model. We used CXCL12 (also known as SDF-1α) and epidermal growth factor (EGF), two well-known extracellular signaling molecules that co-exist in the tumor microenvironment (e.g. lymph nodes or intravasation sites), and a malignant breast tumor cell line, MDA-MB-231, embedded in type I collagen. When subjected to SDF-1α gradients alone, MDA-MB-231 cells migrated up the gradient, and the measured chemosensitivity (defined as the average cell velocity along the direction of the gradient) followed the ligand – receptor (SDF-1α – CXCR4) binding kinetics. On the other hand, when subjected to EGF gradients alone, tumor cells increased their overall motility, but without statistically significant chemotactic (directed) migration, in contrast to previous reports using 2D chemotaxis assays. Interestingly, we found that the chemoinvasive behavior to SDF-1α gradients was abrogated or even reversed in the presence of uniform concentrations of EGF; however...

The Cooperative Roles of Inflammation and Oxidative Stress in the Pathogenesis of Hypertension

Crowley, Steven D.
Fonte: Mary Ann Liebert, Inc. Publicador: Mary Ann Liebert, Inc.
Tipo: Artigo de Revista Científica
Publicado em 01/01/2014 EN
Relevância na Pesquisa
36.06%
Significance: Innate and adaptive immunity play fundamental roles in the development of hypertension and its complications. As effectors of the cell-mediated immune response, myeloid cells and T lymphocytes protect the host organism from infection by attacking foreign intruders with bursts of reactive oxygen species (ROS). Recent Advances: While these ROS may help to preserve the vascular tone and thereby protect against circulatory collapse in the face of overwhelming infection, aberrant elaboration of ROS triggered by immune cells in the absence of a hemodynamic insult can lead to pathologic increases in blood pressure. Conversely, misdirected oxidative stress in cardiovascular control organs, including the vasculature, the kidney, and the nervous system potentiates inflammatory responses, augmenting blood pressure elevation and inciting target organ damage. Critical Issues: Inflammation and oxidative stress thereby act as cooperative and synergistic partners in the pathogenesis of hypertension. Future Directions: Pharmacologic interventions for hypertensive patients will need to exploit this robust bidirectional relationship between ROS generation and immune activation in cardiovascular control organs to maximize therapeutic benefit...

Human Airway Smooth Muscle Promotes Human Lung Mast Cell Survival, Proliferation, and Constitutive Activation: Cooperative Roles for CADM1, Stem Cell Factor, and IL-61

Hollins, Fay; Kaur, Davinder; Yang, Weidong; Cruse, Glenn; Saunders, Ruth; Sutcliffe, Amanda; Berger, Patrick; Ito, Akihiko; Brightling, Christopher E.; Bradding, Peter
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/08/2008 EN
Relevância na Pesquisa
35.94%
The microlocalization of mast cells within specific tissue compartments is thought to be critical for the pathophysiology of many diverse diseases. This is particularly evident in asthma where they localize to the airway smooth muscle (ASM) bundles. Mast cells are recruited to the ASM by numerous chemoattractants and adhere through CADM1, but the functional consequences of this are unknown. In this study, we show that human ASM maintains human lung mast cell (HLMC) survival in vitro and induces rapid HLMC proliferation. This required cell-cell contact and occurred through a cooperative interaction between membrane-bound stem cell factor (SCF) expressed on ASM, soluble IL-6, and CADM1 expressed on HLMC. There was a physical interaction in HLMC between CADM1 and the SCF receptor (CD117), suggesting that CADM1-dependent adhesion facilitates the interaction of membrane-bound SCF with its receptor. HLMC-ASM coculture also enhanced constitutive HLMC degranulation, revealing a novel smooth muscle-driven allergen-independent mechanism of chronic mast cell activation. Targeting these interactions in asthma might offer a new strategy for the treatment of this common disease.

The cooperative roles of the dopamine receptors, D1R and D5R, on the regulation of renal sodium transport

Gildea, John J.; Shah, Ishan T.; Van Sciver, Robert; Israel, Jonathan A.; Enzensperger, Christoph; McGrath, Helen E.; Jose, Pedro A.; Felder, Robin A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
36.06%
Determining the individual roles of the two dopamine D1-like receptors (D1R and D5R) on sodium transport in the human renal proximal tubule has been complicated by their structural and functional similarity. Here we used a novel D5R-selective antagonist (LE-PM436) and D1R or D5R-specific gene silencing to determine second messenger coupling pathways and heterologous receptor interaction between the two receptors. D1R and D5R co-localized in renal proximal tubule cells and physically interact, as determined by co-immunoprecipitation and FRET microscopy. Stimulation of renal proximal tubule cells with fenoldopam (D1R/D5R agonist) led to both adenylyl cyclase and phospholipase C (PLC) activation using real-time FRET biosensors ICUE3 and CYPHR, respectively. Fenoldopam increased cAMP accumulation and PLC activity and inhibited both NHE3 and NaKATPase activities. LE-PM436 and D5R siRNA blocked the fenoldopam-stimulated PLC pathway but not cAMP accumulation, while D1R siRNA blocked both fenoldopam-stimulated cAMP accumulation and PLC signaling. Either D1R or D5R siRNA, or LE-PM436 blocked the fenoldopam dependent inhibition of sodium transport. Further studies using the cAMP-selective D1R/D5R agonist SKF83822 and PLC-selective D1R/D5R agonist SKF83959 confirmed the cooperative influence of the two pathways on sodium transport. Thus...

Cooperative roles of biological flow and surface topography in guiding sperm migration revealed by a microfluidic model

Tung, Chih-kuan; Ardon, Florencia; Fiore, Alyssa; Suarez, Susan S.; Wu, Mingming
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 07/04/2014 EN
Relevância na Pesquisa
46.13%
Successful reproduction in mammals requires sperm to swim against a fluid flow and through the long and complex female reproductive tract before reaching the egg in the oviduct. Millions of them do not make it. Despite the clinical importance, the roles played in sperm migration by the diverse biophysical and biochemical microenvironments within the reproductive tract are largely unknown. In this article, we present the development of a double layer microfluidic device that recreates two important biophysical environments within female reproductive tract: fluid flow and surface topography. The unique feature of the device is that it enables one to study the cooperative roles of fluid flow and surface topography in guiding sperm migration. Using bull sperm as a model system, we found that microfluidic grooves embedded on a channel surface facilitate sperm migration against fluid flows. These findings suggest ways to design in vitro fertilization devices to treat infertility and to develop non-invasive contraceptives that use microarchitectural design to entrap sperm.

In Vitro assays using primary embryonic mouse lymphatic endothelial cells uncover key roles for FGFR1 signalling in lymphangiogenesis

Kazenwadel, J.; Secker, G.; Betterman, K.; Harvey, N.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2012 EN
Relevância na Pesquisa
35.96%
Despite the importance of blood vessels and lymphatic vessels during development and disease, the signalling pathways underpinning vessel construction remain poorly characterised. Primary mouse endothelial cells have traditionally proven difficult to culture and as a consequence, few assays have been developed to dissect gene function and signal transduction pathways in these cells ex vivo. Having established methodology for the purification, short-term culture and transfection of primary blood (BEC) and lymphatic (LEC) vascular endothelial cells isolated from embryonic mouse skin, we sought to optimise robust assays able to measure embryonic LEC proliferation, migration and three-dimensional tube forming ability in vitro. In the course of developing these assays using the pro-lymphangiogenic growth factors FGF2 and VEGF-C, we identified previously unrecognised roles for FGFR1 signalling in lymphangiogenesis. The small molecule FGF receptor tyrosine kinase inhibitor SU5402, but not inhibitors of VEGFR-2 (SU5416) or VEGFR-3 (MAZ51), inhibited FGF2 mediated LEC proliferation, demonstrating that FGF2 promotes proliferation directly via FGF receptors and independently of VEGF receptors in primary embryonic LEC. Further investigation revealed that FGFR1 was by far the predominant FGF receptor expressed by primary embryonic LEC and correspondingly...

Aprendiendo Aprendizaje Cooperativo. Una experiencia en un aula universitaria; Learning Cooperative Learning. An experience in a university classroom

Giménez, Montse
Fonte: Universidad de Alcalá. Escuela Universitaria Cardenal Cisneros Publicador: Universidad de Alcalá. Escuela Universitaria Cardenal Cisneros
Tipo: Artigo de Revista Científica Formato: application/pdf
SPA
Relevância na Pesquisa
36.15%
El siguiente artículo presenta la experiencia llevada a cabo en una asignatura de la Mención en Necesidades Educativas Especiales de los Grados de Magisterio en Educación infantil y Educación Primaria del Centro Universitario Cardenal Cisneros. La asignatura “Intervención en Discapacidad Intelectual, Altas Capacidades y Trastornos Generalizados del Desarrollo” se desarrolló siguiendo estrategias de Aprendizaje Cooperativo (AC) que engloba una organización del espacio, distribución de roles entre los diferentes miembros del grupo, planificación de actividades que favorezcan una interacción positiva y dinámicas de evaluación grupales e individuales. El objetivo de implantar esta metodología es doble: por un lado, aprovechar los beneficios del AC en cualquier proceso de enseñanza y aprendizaje y por otro, proporcionar a los estudiantes una experiencia real y completa de AC (no basada en la teoría) que puedan trasladar fácilmente a su práctica profesional futura, fundamentalmente como herramienta de trabajo en la Atención a la Diversidad.; The following article presents the experience carried out in a subject of the Mention in Special Educational Needs of the Teaching Degrees in Early Childhood Education and Elementary Education from Cardenal Cisneros University College. The subject “Intervention in Intellectual Disabilities...

Towards a complex model of cooperative learning

Arató, Ferenc
Fonte: CIED – Centro Interdisciplinar de Estudos Educacionais/Escola Superior de Educação de Lisboa Publicador: CIED – Centro Interdisciplinar de Estudos Educacionais/Escola Superior de Educação de Lisboa
Tipo: Artigo de Revista Científica
Publicado em /03/2013 ENG
Relevância na Pesquisa
56.46%
Este artigo é uma introdução à teoria do paradigma desconstrutivo de aprendizagem cooperativa. Centenas de estudos provam com evidências o facto de que as estruturas e os processos de aprendizagem cooperativa aumentam o desempenho académico, reforçam as competências de aprendizagem ao longo da vida e desenvolvem competências sociais, pessoais de cada aluno de uma forma mais eficaz e usta, comparativamente às estruturas tradicionais de aprendizagem nas escolas. Enfrentando os desafios dos nossos sistemas educativos, seria interessante elaborar o quadro teórico do discurso da aprendizagem cooperativa, dos últimos 40 anos, a partir de um aspeto prático dentro do contexto teórico e metodológico. Nas últimas décadas, o discurso cooperativo elaborou os elementos práticos e teóricos de estruturas e processos de aprendizagem cooperativa. Gostaríamos de fazer um resumo desses elementos com o objetivo de compreender que tipo de mudanças estruturais podem fazer diferenças reais na prática de ensino e aprendizagem. Os princípios básicos de estruturas cooperativas, os papéis de cooperação e as atitudes cooperativas são os principais elementos que podemos brevemente descrever aqui, de modo a criar um quadro para a compreensão teórica e prática de como podemos sugerir os elementos de aprendizagem cooperativa na nossa prática em sala de aula. Na minha perspetiva...

How to take advantage of “cooperative learning” in the classroom; Cómo aprovechar el “aprendizaje colaborativo” en el aula

Jair Mendoza, César Alberto Collazos
Fonte: Universidad de la Sabana Publicador: Universidad de la Sabana
Tipo: Artigo de Revista Científica
SPA
Relevância na Pesquisa
36.15%
The Cooperative Learning is one of the learning models people are starting to use again in the classroom (although it had been discovered a long time ago). Nevertheless the summit and benefits of this method have been widely demonstrated, people don’t know very much about the way to implement it into the classroom nor the elements that should be considered for its implementation. This article presents some regards to be considered if we want to include this model into our teaching-learning process. In order to reach an effective cooperation, it is necessary to modify teachers’ and students’ roles as well, to make both actors participate more actively into the learning process.; El aprendizaje colaborativo es uno de los modelos de aprendizaje que a pesar de haberse planteado desde hace un largo tiempo, nuevamente comienza a utilizarse dentro del aula de clases. No obstante su auge y la diversidad de estudios que demuestran los beneficios de este método, es muy poco lo que se sabe respecto a cómo puede llevarse a cabo dentro del aula de clases y qué elementos deben considerarse para su implementación. Este artículo presenta algunas consideraciones que deberían tenerse en cuenta, si queremos involucrar este modelo dentro de nuestro proceso de enseñanza-aprendizaje. Para poder lograr una colaboración efectiva...

How to take advantage of “cooperative learning” in the classroom; Cómo aprovechar el “aprendizaje colaborativo” en el aula

Jair Mendoza, César Alberto Collazos
Fonte: Universidad de la Sabana Publicador: Universidad de la Sabana
Tipo: Artigo de Revista Científica
SPA
Relevância na Pesquisa
36.15%
The Cooperative Learning is one of the learning models people are starting to use again in the classroom (although it had been discovered a long time ago). Nevertheless the summit and benefits of this method have been widely demonstrated, people don’t know very much about the way to implement it into the classroom nor the elements that should be considered for its implementation. This article presents some regards to be considered if we want to include this model into our teaching-learning process. In order to reach an effective cooperation, it is necessary to modify teachers’ and students’ roles as well, to make both actors participate more actively into the learning process.; El aprendizaje colaborativo es uno de los modelos de aprendizaje que a pesar de haberse planteado desde hace un largo tiempo, nuevamente comienza a utilizarse dentro del aula de clases. No obstante su auge y la diversidad de estudios que demuestran los beneficios de este método, es muy poco lo que se sabe respecto a cómo puede llevarse a cabo dentro del aula de clases y qué elementos deben considerarse para su implementación. Este artículo presenta algunas consideraciones que deberían tenerse en cuenta, si queremos involucrar este modelo dentro de nuestro proceso de enseñanza-aprendizaje. Para poder lograr una colaboración efectiva...

Cooperative role of RanBP9 and P73 in mitochondria-mediated apoptosis

Liu, T; Roh, S E; Woo, J A; Ryu, H; Kang, D E
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
35.94%
Mitochondrial dysfunction and synaptic damage are critical early features of Alzheimer's disease (AD) associated with amyloid β (Aβ) and τ. We previously reported that the scaffolding protein RanBP9, which is overall increased in AD, simultaneously promotes Aβ generation and focal adhesion disruption by accelerating the endocytosis of APP and β1-integrin, respectively. Moreover, RanBP9 induces neurodegeneration in vitro and in vivo and mediates Aβ-induced neurotoxicity. However, little is known regarding the mechanisms underlying such neurotoxic processes. Here, we show that RanBP9 induces the loss of mitochondrial membrane potential and increase in mitochondrial superoxides associated with decrease in Bcl-2, increase in Bax protein and oligomerization, fragmentation of mitochondria, and cytochrome c release. RanBP9-induced neurotoxic changes are significantly prevented by the mitochondrial fission inhibitor Mdivi-1 and by classical inhibitors of the mitochondrial apoptosis, XIAP, Bcl-2, and Bcl-xl. RanBP9 physically interacts with the tumor suppressor p73 and increases endogenous p73α levels at both transcriptional and post-translational levels;moreover, the knockdown of endogenous p73 by siRNA effectively blocks RanBP9 and Aβ1-42-induced mitochondria-mediated cell death. Conversely...

Cooperative Role of Caveolin-1 and C-Terminal Src Kinase Binding Protein in C-Terminal Src Kinase-Mediated Negative Regulation of c-Src

Place, Aaron T.; Chen, Zhenlong; Bakhshi, Farnaz R.; Liu, Guoquan; O'Bryan, John P.; Minshall, Richard D.
Fonte: The American Society for Pharmacology and Experimental Therapeutics Publicador: The American Society for Pharmacology and Experimental Therapeutics
Tipo: Artigo de Revista Científica
Publicado em /10/2011 EN
Relevância na Pesquisa
35.94%
In the present study, we assessed the cooperative roles of C-terminal Src kinase (Csk) binding protein (Cbp) and Caveolin-1 (Cav-1) in the mechanism of Src family tyrosine kinase (SFK) inhibition by Csk. SFKs are inactivated by phosphorylation of their C-terminal tyrosine by Csk. Whereas SFKs are membrane-associated, Csk is a cytoplasmic protein and therefore requires membrane adaptors such as Cbp or Cav-1 for recruitment to the plasma membrane to mediate SFK inhibition. To determine the specific role of Cav-1 and Cbp in SFK inhibition, we measured c-Src activity in the absence of each membrane adaptor. It is noteworthy that in lungs and fibroblasts from Cav-1(−/−) mice, we observed increased expression of Cbp compared with wild-type (WT) controls. However, both c-Src activity and Csk localization at the membrane were similar between Cav-1(−/−) fibroblasts and WT cells. Likewise, Cbp depletion by small interfering RNA (siRNA) treatment of WT cells had no effect on basal c-Src activity, but it increased the phosphorylation state of Cav-1. Immunoprecipitation then confirmed increased association of Csk with phosphomimicking Cav-1. Knockdown of Cbp by siRNA in Cav-1(−/−) cells revealed increased basal c-Src activity, and re-expression of WT Cav-1 in the same cells reduced basal c-Src activity. Taken together...

Adapting cooperative learning to teach software architecture in multiple-role teams

Chenoweth, Steve; Ardis, Mark; Dugas, Cheryl
Fonte: American Society for Engineering Education Publicador: American Society for Engineering Education
Tipo: Proceedings
EN_US
Relevância na Pesquisa
36.43%
The software architecture process depends on successful teamwork involving cooperation among members of the design team, cooperation between the design team and the clients, and cooperation between the design team and the development organization. Cooperative learning is a pedagogy that directly supports this type of teamwork. Through cooperative learning students realize their interdependence, practice face-to-face communication, recognize their individual accountability to the success of the group, practice interpersonal and small-group skills, and engage in frequent reflective processing of their achievements. We have adapted cooperative learning to teach software architecture in two undergraduate software engineering programs. In traditional cooperative learning, students work on one team for an extended period. This helps foster acceptance of individual differences and promotes successful teamwork. In our courses we kept students together on the same teams, but we wanted students to play multiple roles: clients, architects, and developers. So, we let the teams change roles during the course. That is, for each project one team played the role of architects, while other teams played the roles of clients and developers. Student teams rotated roles on different projects throughout the term. A further variation in cooperative learning is that...