995 resultados para 793


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Inclui bibliografia.

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Inclui notas explicativas e bibliográficas

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The neural cell adhesion molecule (N-CAM) is expressed on the surface of astrocytes, where its homophilic binding leads to the activation of the transcription factor NF-κB. Transfection of astrocytes with a construct encompassing the transmembrane region and the cytoplasmic domain of N-CAM (designated Tm-Cyto, amino acids 685–839 in the full-length molecule) inhibited this activation up to 40%, and inhibited N-CAM-induced translocation of NF-κB to the nucleus. N-CAM also activated NF-κB in astrocytes from N-CAM knockout mice, presumably through binding to a heterophile. This activation, however, was not blocked by Tm-Cyto expression, indicating that the inhibitory effect of the Tm-Cyto construct is specific for cell surface N-CAM. Deletions and point mutations of the cytoplasmic portion of the Tm-Cyto construct indicated that the region between amino acids 780 and 800 were essential for inhibitory activity. This region contains four threonines (788, 793, 794, and 797). Mutation to alanine of T788, T794, or T797, but not T793, abolished inhibitory activity, as did mutation of T788 or T797 to aspartic acid. A Tm-Cyto construct with T794 mutated to aspartic acid retained inhibitory activity but did not itself induce a constitutive NF-κB response. This result suggests that phosphorylation of T794 may be necessary but is not the triggering event. Overall, these findings define a short segment of the N-CAM cytoplasmic domain that is critical for N-CAM-induced activation of NF-κB and may be important in other N-CAM-mediated signaling.

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We previously reported that KIF3A and KIF3B form a heterodimer that functions as a microtubule-based fast anterograde translocator of membranous organelles. We have also shown that this KIF3A/3B forms a complex with other associated polypeptides, named kinesin superfamily-associated protein 3 (KAP3). In the present study, we purified KAP3 protein by immunoprecipitation using anti-KIF3B antibody from mouse testis. Microsequencing was carried out, and we cloned the full-length KAP3 cDNA from a mouse brain cDNA library. Two isoforms of KAP3 exist [KAP3A (793 aa) and KAP3B (772 aa)], generated by alternative splicing in the carboxyl terminus region. Their amino acid sequences have no homology with those of any other known proteins, and prediction of their secondary structure indicated that almost the entire KAP3 molecule is alpha-helical. We produced recombinant KAP3 and KIF3A/3B using a baculovirus-Sf9 expression system. A reconstruction study in Sf9 cells revealed that KAP3 is a globular protein that binds to the tail domain of KIF3A/3B. The immunolocalization pattern of KAP3 was similar to that of KIF3A/3B in nerve cells. In addition, we found that KAP3 does not affect the motor activity of KIF3A/3B. KAP3 was associated with a membrane-bound form of KIF3A/3B in a fractional immunoprecipitation experiment, and since the KIF3 complex was found to bind to membranous organelles in an EM study, KAP3 may regulate membrane binding of the KIF3 complex.

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Prolactin (PRL) induces transcriptional activation of milk protein genes, such as the whey acidic protein (WAP), beta-casein, and beta-lactoglobulin genes, through a signaling cascade encompassing the Janus kinase Jak2 and the mammary gland factor (MGF; also called Stat5), which belongs to the family of proteins of signal transducers and activators of transcription (STAT). We isolated and sequenced from mouse mammary tissue Stat5 mRNA and a previously unreported member, which we named Stat5b (Stat5 is renamed to Stat5a). On the protein level Stat5a and Stat5b show a 96% sequence similarity. The 5' and 3' untranslated regions of the two mRNAs are not conserved. Stat5a comprises 793 amino acids and is encoded by a mRNA of 4.2 kb. The Stat5b mRNA has a size of 5.6 kb and encodes a protein of 786 amino acids. Both Stat5a and Stat5b recognized the GAS site (gamma-interferon-activating sequence; TTCNNNGAA) in vitro and mediated PRL-induced transcription in COS cells transfected with a PRL receptor. Stat5b also induced basal transcription in the absence of PRL. Similar levels of Stat5a and Stat5b mRNAs were found in most tissues of virgin and lactating mice, but a differential accumulation of the Stat5 mRNAs was found in muscle and mammary tissue. The two RNAs are present in mammary tissue of immature virgin mice, and their levels increase up to day 16 of pregnancy, followed by a decline during lactation. The increase of Stat5 expression during pregnancy coincides with the activation of the WAP gene.

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Diferentes abordagens teóricas têm sido utilizadas em estudos de sistemas biomoleculares com o objetivo de contribuir com o tratamento de diversas doenças. Para a dor neuropática, por exemplo, o estudo de compostos que interagem com o receptor sigma-1 (Sig-1R) pode elucidar os principais fatores associados à atividade biológica dos mesmos. Nesse propósito, estudos de Relações Quantitativas Estrutura-Atividade (QSAR) utilizando os métodos de regressão por Mínimos Quadrados Parciais (PLS) e Rede Neural Artificial (ANN) foram aplicados a 64 antagonistas do Sig-1R pertencentes à classe de 1-arilpirazóis. Modelos PLS e ANN foram utilizados com o objetivo de descrever comportamentos lineares e não lineares, respectivamente, entre um conjunto de descritores e a atividade biológica dos compostos selecionados. O modelo PLS foi obtido com 51 compostos no conjunto treinamento e 13 compostos no conjunto teste (r² = 0,768, q² = 0,684 e r²teste = 0,785). Testes de leave-N-out, randomização da atividade biológica e detecção de outliers confirmaram a robustez e estabilidade dos modelos e mostraram que os mesmos não foram obtidos por correlações ao acaso. Modelos também foram gerados a partir da Rede Neural Artificial Perceptron de Multicamadas (MLP-ANN), sendo que a arquitetura 6-12-1, treinada com as funções de transferência tansig-tansig, apresentou a melhor resposta para a predição da atividade biológica dos compostos (r²treinamento = 0,891, r²validação = 0,852 e r²teste = 0,793). Outra abordagem foi utilizada para simular o ambiente de membranas sinápticas utilizando bicamadas lipídicas compostas por POPC, DOPE, POPS e colesterol. Os estudos de dinâmica molecular desenvolvidos mostraram que altas concentrações de colesterol induzem redução da área por lipídeo e difusão lateral e aumento na espessura da membrana e nos valores de parâmetro de ordem causados pelo ordenamento das cadeias acil dos fosfolipídeos. As bicamadas lipídicas obtidas podem ser usadas para simular interações entre lipídeos e pequenas moléculas ou proteínas contribuindo para as pesquisas associadas a doenças como Alzheimer e Parkinson. As abordagens usadas nessa tese são essenciais para o desenvolvimento de novas pesquisas em Química Medicinal Computacional.

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La Comunicación NO Verbal (CNV) es un tipo de comunicación que no siempre se incluye como tal en las competencias y objetivos de las titulaciones académicas y que a menudo se considera sólo desde un punto de vista teórico. Pero, en el ámbito laboral, se exige a los profesionales que sepan controlar a su favor la CNV, en especial a los profesionales de la salud, por el posible impacto sobre el paciente. Mediante formulario on-line, se pidió a los estudiantes matriculados en titulaciones relacionadas y no relacionadas con la sanidad, que valorarán el papel de la CNV en diferentes situaciones de la vida cotidiana. Participaron estudiantes universitarios: U. de Alicante y U. Nacional de Tucumán (Argentina), y de Formación Profesional: IES Leonardo da Vinci (Alicante) e INS Gabriela Mistral (Sant Vicenç dels Horts, Barcelona). Los resultados muestran que los estudiantes universitarios consideran más importante y valoran mejor la CNV que los de Formación Profesional. Sin embargo, no se aprecian diferencias significativas entre estudiantes de titulaciones sanitarias y no sanitarias en ninguno de los dos niveles académicos. Ante estos resultados hacemos una llamada a la reflexión sobre la importancia que debería adquirir la práctica de la CNV en las titulaciones sanitarias.

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El objetivo del trabajo de la red es, por un lado, analizar la satisfacción de los alumnos con el Trabajo Fin de Grado (TFG) y, por otro, estudiar la percepción que tienen los alumnos que finalizan estudios sobre las capacidades de empleabilidad alcanzadas. Para lograr estos objetivos, se han realizado dos encuestas dirigidas a los alumnos de TFG y a los alumnos de últimos cursos de las titulaciones en las que impartimos docencia. Los resultados muestran la satisfacción del alumnado con el TFG y las capacidades a mejorar con relación a la empleabilidad: iniciativa, negociación, detección de nuevas oportunidades, uso de herramientas informáticas, búsqueda de ideas y soluciones, hablar en público, redactar informes e idiomas.

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Bill of sale between Thomas Sawyer, Jacob Adams, and Isaac Sawyer, all of Falmouth, Massachusetts, and Ebenezer Storer and William Winthrop for the sloop Cyrus.

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One folded folio-sized leaf containing handwritten financial entries compiled by William Winthrop from February 1793 to July 1793. The entry notes that the sloop made a "voyage to the West Indies" between February and May 1793.

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One-folio page containing handwritten financial entries compiled by Treasurer Ebenezer Storer from February 1793 to December 1793.

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Accounting records related to the wood brought by the sloop between May and September 1793 on three slips of paper bound with thread. The last page contains a certification signed by William Winthrop on September 9, 1793 of the sale of wood in Charlestown.

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Thirteen statements of trips of the Cyrus between April 23, 1795 and December 9, 1795 signed by Steward Caleb Gannett. The statements list the cords of wood added to the College's supply and the cords sold. The statements are on thirteen slips of paper of various sizes bound with thread.

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Copy of the vessel enrollment certificate for the sloop Cyrus on one folio-sized leaf. All ships owned by United States citizens were required by federal law to be registered.