OS SINAIS NO EVANGELHO DE JOÃO: EXEGESE DE JOÃO 6.1-15

Esta dissertação analisará a recorrência do termo sinal no Quarto Evangelho, tendo como paradigma a exegese de João 6.1-15, perícope denominada como multiplicação dos pães e peixes. O texto da multiplicação dos pães e peixes se insere no Bloco dos Sinais (capítulo 1-12), o qual é marcado por sete sinais, sendo eles: o casamento de Caná (2.1-11); a cura do filho do oficial do rei (4.43-54); a cura de um paralítico de Betesda (5.1-15), a multiplicação dos pães e peixes (6.1-15); andar sobre as águas (6.16-21); cura do cego de nascença (9.1-41) e a ressurreição de Lázaro (11.1-45). A pesquisa revelou, além das peculiaridades narrativas, semióticas e hermenêuticas, próprias do Evangelho de João, que o termo sinal enquadra a narrativa, além de estruturar e proporcionar cadência para o texto joanino. Nota-se tangência e diálogo entre os sinais, de modo que a perícope de João 6.1-15 exerce papel central no Bloco da Paixão por ser um texto identitário dos leitores, bem como da comunidade joanina.

À l'origine du concept de l'élection divine : critique des sources de Jg 10, 16-11, 40 ; I S 9, 1-10, 16 ; I S 11, 1-15

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

À l'origine du concept de l'élection divine : critique des sources de Jg 10, 16-11, 40 ; I S 9, 1-10, 16 ; I S 11, 1-15

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Galanin N-Terminal fragment (1-15) enhances the antidepressant effects of the 5-HT1A receptor agonist 8-OH-DPAT in the Forced Swimming Test.

Galanin and Galanin (1-15) [GAL(1-15)] are implicated in anxiety- and depression related behaviors. Moreover, Galanin modulates 5-HT1A receptor (5-HT1AR) function at autorreceptor and postsynaptic level in the brain. In this study, we have analysed the ability of GAL(1-15) to modulate the effects of the 8-OH-DPAT agonist in the Forced Swimming Test (FST). Groups of rats were assessed in the FST. In the first set of experiments, to evaluate the interactions of 8-OH-DPAT and GAL(1-15), rats received subcutaneously (s.c) the effective doses of 8-OH-DPAT (0.25mg/Kg) 60min before the test and intracerebroventricularly (icv) GAL(1-15)1nmol 15min before the tests alone or in combination. In the second set of experiments, groups of rats received s.c. 8-OH-DPAT (0.125mg/Kg), icv GAL(1-15) 1nmol and icv the GALR2 antagonist M871 3 nmol alone or in combination. The locomotor activity was analysed in the open field test. GAL(1-15) 1nmol enhanced the antidepressant-like effects mediated by the effective dose of the 8-OH-DPAT. GAL(1-15) significantly decreased the immobility (p<0.05) and climbing (p<0.05) and increased the swimming (p<0.01) behaviour induced by an effective dose of 8-OH-DPAT (0.25mg/Kg) in FST. Moreover, after coadministration of GAL(1-15) and threshold dose of 8-OH-DPAT (0.125mg/Kg) a significant decreased appeared in immobility (p<0.01) and climbing (p<0.01) and increased the swimming behavior (p<0.001) vs 8-OH-DPAT group. Moreover, M871 blocked completely this interaction. These results indicate that GAL(1-15) enhances the antidepressant effects induced by 8-OH-DPAT in the FST. These findings may give the basis for the development of novel therapeutic drugs. This study was supported by Junta de Andalucía CVI6476.

Galanin and galanin fragment 1-15 modulate antidepressant responses by targeting 5-HT1AR-GALR heteroreceptor complexes of the ascending midbrain serotonin pathways.

Mood disorders, including depression and anxiety, are among the most prevalent mental illnesses with high socioeconomic impact. Although the underlying mechanisms have not yet been clearly defined in the last decade the importance of the role of neuropeptides, including Galanin (GAL), and/or their receptors in the treatment of stress-related mood disorders is becoming increasingly apparent. GAL is involved in mood regulation, including depression-related and anxiety-like behaviors. Activation of GALR1 and GALR3 receptors results in a depression like behavior while stimulation of GALR2 receptor leads to anti-depressant-like effects. Moreover, GAL modulates 5-HT1A receptors (5-HT1AR), a key receptor in depression at autoreceptor and postsynaptic level in the brain. This interaction can in part be due to the existence of GALR1-5-HT1AR heteroreceptor complexes in discrete brain regions [1]. Not only GAL but also the N-terminal fragments like GAL(1-15) are active in the Central Nervous System [2, 3]. Recently, we described that GAL(1-15) induces strong depression-related and anxiogenic-like effects in rats, and these effects were significantly stronger than the ones induced by GAL [4]. The GALR1-GALR2 heteroreceptor complexes in the dorsal hippocampus and especially in the dorsal raphe (DR), areas rich in GAL(1-15) binding sites [5] were involved in these effects [4, 6] and demonstrated also in cellular models. In the present study, we have analyzed the ability of GAL(1-15) to modulate 5-HT1AR located at postjunctional sites and at the soma-dendritic level in rats. We have analyzed the effect of GAL(1-15) on the 5-HT1AR-mediated response in a behavioral test of depression and the involvement of the GALR2 in these effects. GAL(1-15) enhanced the antidepressant effects induced by the 5-HT1AR agonist 8-OH-DPAT in the forced swimming test [7]. These effects were stronger than the ones induced by GAL. The mechanism of this action involved interactions at the receptor level in the plasma membrane with changes also at the transcriptional level. Thus, GAL(1-15) affected the binding characteristics as well as the mRNA level of 5-HT1AR in the dorsal hippocampus and DR. GALR2 was involved in these effects, since the specific GALR2 antagonist M871 blocked GAL(1-15) mediated actions at the behavioral and receptor level [7]. Furthermore, the results on the proximity ligation assay (PLA) in this work suggest the existence of GALR1-GALR2-5-HT1AR heteroreceptor complexes since positive PLA were obtained for both GALR1-5-HT1AR and GALR2-5-HT1AR complexes in the DR and hippocampus. Moreover the studies on RN33B cells, where GALR1, GALR2 and 5-HT1AR exist [4], also showed PLA-positive clusters indicating the existence of GALR1-5-HT1AR and GALR2-5-HT1AR complexes in these cells [7]. In conclusion, our results indicate that GAL(1–15) enhances the antidepressant effects induced by the 5-HT1AR agonist 8-OH-DPAT probably acting on GALR1-GALR2-5-HT1AR heteroreceptor located at postjunctional sites and at the soma-dendritic level. The development of new drugs specifically targeting these heteroreceptor complexes may offer a novel strategy for treatment of depression. This work has been supported by Junta de Andalucia CVI646 1. Borroto-Escuela, D.O., et al., Galanin receptor-1 modulates 5-hydroxtryptamine-1A signaling via heterodimerization. Biochem Biophys Res Commun, 2010. 393(4): p. 767-72. 2. Hedlund, P.B. and K. Fuxe, Galanin and 5-HT1A receptor interactions as an integrative mechanism in 5-HT neurotransmission in the brain. Ann N Y Acad Sci, 1996. 780: p. 193-212. 3. Diaz-Cabiale, Z., et al., Neurochemical modulation of central cardiovascular control: the integrative role of galanin. EXS, 2010. 102: p. 113-31. 4. Millon, C., et al., A role for galanin N-terminal fragment (1-15) in anxiety- and depression-related behaviors in rats. Int J Neuropsychopharmacol, 2015. 18(3). 5. Hedlund, P.B., N. Yanaihara, and K. Fuxe, Evidence for specific N-terminal galanin fragment binding sites in the rat brain. Eur J Pharmacol, 1992. 224(2-3): p. 203-5. 6. Borroto-Escuela, D.O., et al., Preferential activation by galanin 1-15 fragment of the GalR1 protomer of a GalR1-GalR2 heteroreceptor complex. Biochem Biophys Res Commun, 2014. 452(3): p. 347-53. 7. Millon, C., et al., Galanin (1-15) enhances the antidepressant effects of the 5-HT1A receptor agonist 8-OH-DPAT: involvement of the raphe-hippocampal 5-HT neuron system. Brain Struct Funct, 2016.

Galanin n-terminal gragment (1-15) modifies the 5-HT1A receptor against [H3]-8-OH-DPAT binding in the dorsal raphe and hippocampus of the rat

We have described that Galanin N-terminal fragment (1-15) [GAL(1-15)] is associated with depressive effects and also modulates the antidepressant effects induced by the 5-HT1A receptor (5-HT1AR) agonist 8-OH-DPAT. The aim of this study is to analyze the ability of GAL(1-15) to modulate 5-HT1AR at the autoreceptor and postsynaptic receptor level in rats by using quantitative autoradiography. We analyzed the effect of intracerebroventricular GAL(1-15)-3nmol (n=6) or aCSF (n=6), 10 minutes, 2 and 5 hours after the injection, on the binding characteristics of the 5-HT1AR agonist [H3]-8-OH-DPAT in sections of the Dorsal Raphe (DR) and Dorsal Hippocampus, specifically CA1 and Dentate Gyrus (DG). Student’s t-test was used to compare the experimental groups. GAL(1-15) produced a time-dependent effect on the binding of [H3]-8-OH-DPAT. In CA1 and DG, a significant increase in the KD and Bmax was observed, by 90%(p<0.05), at 10 minutes and 2 hours after injection. However, 5 hours after GAL(1-15) the only significant change remaining was the increase in Bmax at the DG. The coinjection of the GALR2 antagonist M871 blocked significantly the effects induced by GAL(1-15) in both areas. In DR, 2 hours after injection GAL(1-15) only produced a decrease in the Bmax by 20%(p<0.05). These results indicate that GAL(1-15) interacts with 5-HT1AR at the receptor level in DR and Dorsal Hippocampus. Therapeutic strategies based on these results could be developed for the treatment of depression disorders. This work has been supported by Junta de Andalucia CVI646 and Spanish Ministry of Economy PSI2013-44901-P.

Experimental Reinforcement of Wood Beams

Rehabilitation is becoming more and more usual in the construction sector in Portugal. The introduction of newer construction materials and technical know-how of integrating different materials for achieving desired engineering goals is an important step to the development of the sector. Wood industry is also getting more and more adapted to composite technologies with the introduction of the so called “highly engineered wood products” and with the use of modification treatments. This work is an attempt to explain the viability of using stainless steel and glass fibre reinforced polymer (GFRP) as reinforcements in wood beams. This thesis specifically focuses on the flexural behaviour of Portuguese Pine unmodified and modified wood beams. Two types of modification were used: 1,3-dimethylol-4,5- dihydroxyethyleneurea (DMDHEU) resin and amid wax. The behaviour of the material was analysed with a nonlinear model. The latter model simulates the behaviour of the reinforced wood beams under flexural loading. Small-scale beams (1:15) were experimented in flexural bending and the experimental results obtained were compared with the analytical model results. The experiments confirm the viability of the reinforcing schemes and the working procedures. Experimental results showed fair agreement with the nonlinear model. A strength increase between 15% and 80% was achieved. Stiffness increased by 40% to 50% in beams reinforced with steel but no significant increase was achieved with the glass fibre reinforcement.

Equações de predição da composição química corporal a partir do corte da 9-10-11ª costelas de bovinos castrados Nelore

Objetivou-se obter equações de regressão linear simples para estimativa da composição química corporal de novilhos Nelore a partir da composição química do corte da 9-10-11ª costelas. Foram utilizados 27 bovinos em confinamento, com 21 a 31 meses de idade e 338,0 a 503,6 kg de peso corporal. do total, foram abatidos seis animais (referência) ao início do experimento para estimativa da composição química corporal. A composição química em água, proteína, EE e cinzas foi determinada no corte da 9-10-11ª costelas e nos tecidos corporais. As equações de regressão para estimativa do peso de corpo vazio (PCVZ) a partir dos pesos de jejum (PV) e carcaça quente (PCQ) foram PCVZ = 0,8726 PV - 2,7399 e PCVZ = 1,5350 PCQ + 13,598 (R² = 0,98). O ganho de 1 kg de PCVZ correspondeu a aproximadamente 1,15 kg de PV. A porcentagem de água no corpo vazio (CVz) esteve altamente correlacionada às porcentagens de água (R² = 0,98) e EE (R² = 0,91) no corte das costelas. A equação mais indicada foi a desenvolvida a partir da porcentagem de água no corte das costelas (Sx, y = 0,46). Verificou-se alta correlação entre a porcentagem de EE no CVz e a porcentagem de EE (R² = 0,95) no corte das costelas, portanto, a equação %EE CVz = 0,9662%EE costelas + 1,5294 pode ser utilizada para estimativa da composição do CVz em EE. O mesmo ocorreu para a porcentagem de cinzas, sendo recomendada a equação %MM CVz = 0,5915%MM costelas + 0,7619 (R² = 0,88). A composição química percentual em água, EE e minerais no corte das 9-10-11ª costelas permitiu estimar com acuidade a composição do corpo vazio.

Map of Cambridge and Somerville, Mass

"318 D."

Boston Harbor Islands National Recreation Area

prepared for the National Park Service by the Metropolitan Area Planning Council.

Map of town of Walpole, Massaachusetts

Peter Boghossian, town engineer.

City of New-York.

Scale ca. 1:15,000.

The harbour of St. Augustín in East Florida.

Scale approximately 1:32,500.