Mastoparan, a novel mitogen for Swiss 3T3 cells, stimulates pertussis toxin-sensitive arachidonic acid release without inositol phosphate accumulation

Mastoparan, a basic tetradecapeptide isolated from wasp venom, is a novel mitogen for Swiss 3T3 cells. This peptide induced DNA synthesis in synergy with insulin in a concentration-dependent manner; half-maximum and maximum responses were achieved at 14 and 17 microM, respectively. Mastoparan also stimulated DNA synthesis in the presence of other growth promoting factors including bombesin, insulin-like growth factor-1, and platelet-derived growth factor. The synergistic mitogenic stimulation by mastoparan can be dissociated from activation of phospholipase C. Mastoparan did not stimulate phosphoinositide breakdown, Ca2+ mobilization or protein kinase C-mediated phosphorylation of a major cellular substrate or transmodulation of the epidermal growth factor receptor. In contrast, mastoparan stimulated arachidonic acid release, prostaglandin E2 production, and enhanced cAMP accumulation in the presence of forskolin. These responses were inhibited by prior treatment with pertussis toxin. Hence, mastoparan stimulates arachidonic acid release via a pertussis toxin-sensitive G protein in Swiss 3T3 cells. Arachidonic acid, like mastoparan, stimulated DNA synthesis in the presence of insulin. The ability of mastoparan to stimulate mitogenesis was reduced by pertussis toxin treatment. These results demonstrate, for the first time, that mastoparan stimulates reinitiation of DNA synthesis in Swiss 3T3 cells and indicate that this peptide may be a useful probe to elucidate signal transduction mechanisms in mitogenesis.

Isolation of a novel monkey adenovirus reveals a new phylogenetic clade in the evolutionary history of simian adenoviruses

Adenoviruses of primates include human (HAdV) and simian (SAdV) isolates classified into 8 species (Human Adenovirus A to G, and Simian Adenovirus A). In this study, a novel adenovirus was isolated from a colony of cynomolgus macaques (Macaca fascicularis) and subcultured in VERO cells. Its complete genome was purified and a region encompassing the hexon gene, the protease gene, the DNA binding protein (DBP) and the 100 kDa protein was amplified by PCR and sequenced by primer walking. Sequence analysis of these four genes showed that the new isolate had 80% identity to other primate adenoviruses and lacked recombination events. The study of the evolutionary relationships of this new monkey AdV based on the combined sequences of the four genes supported a close relationship to SAdV-3 and SAdV-6, lineages isolated from Rhesus monkeys. The clade formed by these three types is separated from the remaining clades and establishes a novel branch that is related to species HAdV-A, F and G. However, the genetic distance corresponding to the newly isolated monkey AdV considerably differs from these as to belong to a new, not yet established species. Results presented here widen our knowledge on SAdV and represents an important contribution to the understanding of the evolutionary history of primate adenoviruses.

Isolation of a novel monkey adenovirus reveals a new phylogenetic clade in the evolutionary history of simian adenoviruses

Adenoviruses of primates include human (HAdV) and simian (SAdV) isolates classified into 8 species (Human Adenovirus A to G, and Simian Adenovirus A). In this study, a novel adenovirus was isolated from a colony of cynomolgus macaques (Macaca fascicularis) and subcultured in VERO cells. Its complete genome was purified and a region encompassing the hexon gene, the protease gene, the DNA binding protein (DBP) and the 100 kDa protein was amplified by PCR and sequenced by primer walking. Sequence analysis of these four genes showed that the new isolate had 80% identity to other primate adenoviruses and lacked recombination events. The study of the evolutionary relationships of this new monkey AdV based on the combined sequences of the four genes supported a close relationship to SAdV-3 and SAdV-6, lineages isolated from Rhesus monkeys. The clade formed by these three types is separated from the remaining clades and establishes a novel branch that is related to species HAdV-A, F and G. However, the genetic distance corresponding to the newly isolated monkey AdV considerably differs from these as to belong to a new, not yet established species. Results presented here widen our knowledge on SAdV and represents an important contribution to the understanding of the evolutionary history of primate adenoviruses.

Podocalyxin is a novel polysialylated neural adhesion protein with multiple roles in neural development and synapse formation

Neural development and plasticity are regulated by neural adhesion proteins, including the polysialylated form of NCAM (PSA-NCAM). Podocalyxin (PC) is a renal PSA-containing protein that has been reported to function as an anti-adhesin in kidney podocytes. Here we show that PC is widely expressed in neurons during neural development. Neural PC interacts with the ERM protein family, and with NHERF1/2 and RhoA/G. Experiments in vitro and phenotypic analyses of podxl-deficient mice indicate that PC is involved in neurite growth, branching and axonal fasciculation, and that PC loss-of-function reduces the number of synapses in the CNS and in the neuromuscular system. We also show that whereas some of the brain PC functions require PSA, others depend on PC per se. Our results show that PC, the second highly sialylated neural adhesion protein, plays multiple roles in neural development.

Temps de desig: la novel-la de Jeanne Hersch

L'única novel·la publicada per la filòsofa Jeanne Hersch (Temps alternés, 1942) consisteix principalment en una reflexió sobre el temps i sobre la relació del subjecte amb l'Altre. Descriu dos tipus de temporalitat: un present etern, en què la narradora adolescent viu l'instant sense plantejar-se cap fita, i un present de maduresa fet de records i de projeccions cap al futur. Exposa també dues possibilitats de relació entre el subjecte i l'Altre: la separació total, marcada per l'hermetisme del propi cos, i la fusió, encarnada en el cos porós de la dona embarassada. Aquestes alternatives es resumeixen en l'oposició entre amor i desig.

Generation of biological association networks: A novel strategy to detect new targets in cancer therapy

The aim of this work was to design a novel strategy to detect new targets for anticancer treatments. The rationale was to build Biological Association Networks from differentially expressed genes in drug-resistant cells to identify important nodes within the Networks. These nodes may represent putative targets to attack in cancer therapy, as a way to destabilize the gene network developed by the resistant cells to escape from the drug pressure. As a model we used cells resistant to methotrexate (MTX), an inhibitor of DHFR. Selected node-genes were analyzed at the transcriptional level and from a genotypic point of view. In colon cancer cells, DHFR, the AKR1 family, PKC¿, S100A4, DKK1, and CAV1 were overexpressed while E-cadherin was lost. In breast cancer cells, the UGT1A family was overexpressed, whereas EEF1A1 was overexpressed in pancreatic cells. Interference RNAs directed against these targets sensitized cells towards MTX.

Temps de desig: la novel-la de Jeanne Hersch

L'única novel·la publicada per la filòsofa Jeanne Hersch (Temps alternés, 1942) consisteix principalment en una reflexió sobre el temps i sobre la relació del subjecte amb l'Altre. Descriu dos tipus de temporalitat: un present etern, en què la narradora adolescent viu l'instant sense plantejar-se cap fita, i un present de maduresa fet de records i de projeccions cap al futur. Exposa també dues possibilitats de relació entre el subjecte i l'Altre: la separació total, marcada per l'hermetisme del propi cos, i la fusió, encarnada en el cos porós de la dona embarassada. Aquestes alternatives es resumeixen en l'oposició entre amor i desig.

Emergence of novel domains in proteins

Proteins are composed of a combination of discrete, well-defined, sequence domains, associated with specific functions that have arisen at different times during evolutionary history. The emergence of novel domains is related to protein functional diversification and adaptation. But currently little is known about how novel domains arise and how they subsequently evolve. To gain insights into the impact of recently emerged domains in protein evolution we have identified all human young protein domains that have emerged in approximately the past 550 million years. We have classified them into vertebrate-specific and mammalian-specific groups, and compared them to older domains. We have found 426 different annotated young domains, totalling 995 domain occurrences, which represent about 12.3% of all human domains. We have observed that 61.3% of them arose in newly formed genes, while the remaining 38.7% are found combined with older domains, and have very likely emerged in the context of a previously existing protein. Young domains are preferentially located at the N-terminus of the protein, indicating that, at least in vertebrates, novel functional sequences often emerge there. Furthermore, young domains show significantly higher non-synonymous to synonymous substitution rates than older domains using human and mouse orthologous sequence comparisons. This is also true when we compare young and old domains located in the same protein, suggesting that recently arisen domains tend to evolve in a less constrained manner than older domains. We conclude that proteins tend to gain domains over time, becoming progressively longer. We show that many proteins are made of domains of different age, and that the fastest evolving parts correspond to the domains that have been acquired more recently.

EL Portafolio docente como estrategia formativa innovadora del profesorado novel universitario. Un estudio de casos

Este artículo sintetiza los resultados y las principales conclusiones de una investigación realizada en la Universidad de Barcelona sobre el tema del portafolio docente, un fenómeno bastante reciente en el campo de la formación del profesorado en general, y en la del docente universitario en particular. La introducción de esta herramienta en la Enseñanza universitaria se debe a la Asociación Canadiense de Profesores de Universidad (en la década de los ochenta), que la empleó para la habilitación y la evaluación de docentes. Sin embargo, en este trabajo se parte de la idea de que los portafolios docentes tienen también una vertiente formativa y resultan útiles en la mejora y el desarrollo profesional del profesorado universitario novel. Explorar este aspecto es el objetivo de nuestro estudio. Se ha elegido, como campo de aplicación, el profesorado novel de la Universidad de Barcelona, que ha elaborado un portafolio docente en los cursos de Iniciación en la Docencia Universitaria. El enfoque usado ha sido cualitativo y como estrategia metodológica hemos optado por el estudio de casos múltiple, dado que la muestra está constituida por 10 profesores universitarios noveles de diferentes áreas de conocimiento. Para recoger y registrar la información, los instrumentos empleados fueron la entrevista en profundidad y el análisis de documentos. Los resultados apuntan a que el verdadero valor del portafolio docente reside en su potencial formativo y para el desarrollo profesional del profesorado universitario novel. También revelan que el portafolio es una herramienta valiosa para un nuevo profesionalismo docente, que se orienta a la reflexión sobre la propia práctica docente y al desarrollo de una enseñanza más acorde con las exigencias de la nueva sociedad del conocimiento.

Therapeutic targeting of tumor growth and angiogenesis with a novel anti-S100A4 monoclonal antibody

S100A4, a member of the S100 calcium-binding protein family secreted by tumor and stromal cells, supports tumorigenesis by stimulating angiogenesis. We demonstrated that S100A4 synergizes with vascular endothelial growth factor (VEGF), via the RAGE receptor, in promoting endothelial cell migration by increasing KDR expression and MMP-9 activity. In vivo overexpression of S100A4 led to a significant increase in tumor growth and vascularization in a human melanoma xenograft M21 model. Conversely, when silencing S100A4 by shRNA technology, a dramatic decrease in tumor development of the pancreatic MiaPACA-2 cell line was observed. Based on these results we developed 5C3, a neutralizing monoclonal antibody against S100A4. This antibody abolished endothelial cell migration, tumor growth and angiogenesis in immunodeficient mouse xenograft models of MiaPACA-2 and M21-S100A4 cells. It is concluded that extracellular S100A4 inhibition is an attractive approach for the treatment of human cancer.

Gone with the Wind and the Southern Way of Life: the Civil War as described in Margaret Mitchell’s Novel

This essay examines the American Civil War of 1861 – 1865, which is also known as the bloodiest war that the United States has ever experienced. The pretext for the war was the abolition of slavery in the South, and after many battles the Southern states lost: as a consequence, they experienced major changes in their economic and social life. This interesting piece from American history can be traced out throughout the characters’ lives in the novel Gone with the Wind which has been thoroughly analyzed in order to draw nearer and to comprehend the changes in the Southern way of life before and after the war. The author, Margaret Mitchell, was born in Atlanta, Georgia, and grew up with the stories about the war. As a result, Gone with the Wind studies not only its causes, but also the years after its end – a period which is not generally a subject of history and receives little attention – and the effects that such reversals have on former planters and slaves. From the position of contemporaneity, the reader can see that such changes in a society do not end with the laying down of an act, or in this case the end of the war, but they continue during many years; thus, the modern world can draw conclusions and lessons for events that are happening at the moment.

El profesorado novel de geografía e historia y el aprendizaje de tecnologías

Esta comunicación presenta un modelo de experiencia didáctica que se plantea el uso de tecnologiasdigitales y de internet en clase de Geografía e Historia a partir de los recursos tecnològicoshabituales que existan en un centro educativo y de los enseres tecnológicos que utilizaregularmente el alumnado.Se basa en diversas ejemplificaciones realizadas entre 2006 y 2013 con alumnado deGeografia e Historia del Màster de Secundaria de la UB, del antiguo CAP de Geografia e Historiadel ICE de la UB y de los cursos para profesorado novel interino del Departament d’Ensenyamentde la Generalitat de Catalunya. En la diversas actuaciones se fueron considerando losdiversos parámetros que finalmente han servido para determinar la estructura de la experienciaaplicada recientemente. Se trata de un modelo basado en tres apartados, donde el primeroes una exposición de tipo transmisivo que plantearía la teoria de toda la actividad a realizar.Una segunda parte propone un trabajo en grupo de descubrimiento tecnológico y deplanificación temática de la materia. Finalmente se fija una exposición del producto realizado como resultado del aprendizaje conseguido.

El profesorado novel de geografía e historia y el aprendizaje de tecnologías

Esta comunicación presenta un modelo de experiencia didáctica que se plantea el uso de tecnologiasdigitales y de internet en clase de Geografía e Historia a partir de los recursos tecnològicoshabituales que existan en un centro educativo y de los enseres tecnológicos que utilizaregularmente el alumnado.Se basa en diversas ejemplificaciones realizadas entre 2006 y 2013 con alumnado deGeografia e Historia del Màster de Secundaria de la UB, del antiguo CAP de Geografia e Historiadel ICE de la UB y de los cursos para profesorado novel interino del Departament d’Ensenyamentde la Generalitat de Catalunya. En la diversas actuaciones se fueron considerando losdiversos parámetros que finalmente han servido para determinar la estructura de la experienciaaplicada recientemente. Se trata de un modelo basado en tres apartados, donde el primeroes una exposición de tipo transmisivo que plantearía la teoria de toda la actividad a realizar.Una segunda parte propone un trabajo en grupo de descubrimiento tecnológico y deplanificación temática de la materia. Finalmente se fija una exposición del producto realizado como resultado del aprendizaje conseguido.

Coregulator Control of Androgen Receptor Action by a Novel Nuclear Receptor-Binding Motif

The androgen receptor (AR) is a ligand-activated transcription factor that is essential for prostate cancer development. It is activated by androgens through its ligand-binding domain (LBD), which consists predominantly of 11 α-helices. Upon ligand binding, the last helix is reorganized to an agonist conformation termed activator function-2 (AF-2) for coactivator binding. Several coactivators bind to the AF-2 pocket through conserved LXXLL or FXXLF sequences to enhance the activity of the receptor. Recently, a small compound-binding surface adjacent to AF-2 has been identified as an allosteric modulator of the AF-2 activity and is termed binding function-3 (BF-3). However, the role of BF-3 in vivo is currently unknown, and little is understood about what proteins can bind to it. Here we demonstrate that a duplicated GARRPR motif at the N terminus of the cochaperone Bag-1L functions through the BF-3 pocket. These findings are supported by the fact that a selective BF-3 inhibitor or mutations within the BF-3 pocket abolish the interaction between the GARRPR motif(s) and the BF-3. Conversely, amino acid exchanges in the two GARRPR motifs of Bag-1L can impair the interaction between Bag-1L and AR without altering the ability of Bag-1L to bind to chromatin. Furthermore, the mutant Bag-1L increases androgen-dependent activation of a subset of AR targets in a genome-wide transcriptome analysis, demonstrating a repressive function of the GARRPR/BF-3 interaction. We have therefore identified GARRPR as a novel BF-3 regulatory sequence important for fine-tuning the activity of the AR.