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O presente artigo se desenvolve a partir da sugestão de perguntas-chave sobre as Soluções baseadas na Natureza (SbN) e sua aplicabilidade no contexto latino-americano. Faz uma revisão bibliográfica e uma investigação temporal do termo com o objetivo de apresentar como as SbN vêm sendo conceitualizadas globalmente, refletindo sobre como vêm sendo compreendidas e aplicadas na América Latina. Ao apresentar dois estudos de caso, um no Brasil e outro no Peru, o artigo não apenas delineia uma reflexão sobre as SbN no contexto latino-americano, mas evidencia lacunas, lições aprendidas e sugere passos futuros que poderão contribuir com o desenvolvimento conceitual, o planejamento, a implementação e escalamento das SbN na região.

This chapter highlights how cocreation processes have been applied for the implementation of nature-based solutions (NBS) in different organizational systems, governance, and cultural settings around the world. The cases are from Peru, the United States, and Korea. The cases show how collaborative governance arrangements for NBS have played out in different contexts. Finally, reflections on the cases are carried out considering the perspectives and limitations of cocreation for NBS delivery.

The present work aims to investigate the academic life-span of courses in Eastern and South-Eastern European languages and literatures at Ca’ Foscari University of Venice, currently taught in the Department of Linguistic and Cultural Comparative Studies. It presents a historical reconstruction of the teaching of Albanian, Bulgarian, Czech, Polish, Russian, Slovenian and Serbo-Croatian languages and literatures from their emergence as academic disciplines to the present day when they continue to be taught at the undergraduate and the graduate level (except for Bulgarian). The section on Russian language and literature is further enriched with a biography of Evel Gasparini. As the article shows, each language has followed a different path, but, with the important exception of Russian language and literature, what they have in common is the long-term attempt and the strong will to maintain their presence in the academic curricula in spite of the continuous fluctuation of conditions that has shaped their history at Ca’ Foscari.

The critical issue of floods in Brazilian cities is a consequence of an accelerated and disordered occupation and urbanization process, which results in excessive soil waterproofing, removal of riparian vegetation, silting of rivers and streams, water pollution, among others. In the last decades, the use of conventional drainage techniques has resulted in many problems, due to the fast flow of water to downstream and the pollutant loads that flow to the watercourses. Through Green Infrastructure it is possible to promote urban rainwater storage and infiltration, reducing the probability of flooding, and allowing for the retention of pollutants and consequent improvement of water quality in urban water systems. In this study, the application of Blue-Green Infrastructure (BGI) techniques for the reduction of peak flow and improve the water quality are proposed for the Jacarezinho watershed, located in the Municipality of São Paulo. Hydrological simulations of the proposed solutions indicated a reduction of about 36% of the peak flow, which highlights the relevance of BGI. Unlike the Brazilian conventional drainage that practice the construction of monofunctional flood storage reservoirs (called in Brazil as “piscinões”), the BGI also promotes a harmonious and balanced interaction between the population and the urban landscape.

O Projeto Jaguaré reuniu uma equipe multidisciplinar formada por engenheiros, arquitetos urbanistas e de paisagem a fim de desenvolver uma metodologia replicável para a requalificação das bacias hidrográficas da Região Metropolitana de São Paulo. Como estudo de caso piloto foi abordada a bacia do córrego Jaguaré, devido à existência de diversos tipos de uso e ocupação do solo, representativos das outras bacias hidrográficas da RMSP. Uma metodologia sistêmica foi desenvolvida, baseada na integração de estratégias e dispositivos de Infraestrutura Verde nas diversas escalas da paisagem urbana e periurbana, capazes de gerar redundância ao sistema de drenagem instalado e contribuir para o metabolismo urbano principalmente ao lidar com os problemas relacionados ao manejo dos volumes e da qualidade das águas de chuva. O presente artigo apresenta um panorama dos resultados atingidos pelo Projeto Jaguaré.

1 This study reports on the pharmacological characterization of ZP120, a novel ligand of the nociceptin/orphanin FQ (N/OFQ) peptide receptor, NOP. ZP120 is a structure inducing probes modified NOP ligand: Zealand Pharma proprietary SIP technology was used to increase the enzymatic stability and half-life of peptide. 2 In vitro, ZP120 mimicked the inhibitory eAects of N/OFQ in the electrically stimulated mouse vas deferens, showing however higher potency (pEC50 8.88 vs 7.74), lower maximal eAects (Emax 69+5% vs 91+2%), and slower onset of action. Like N/OFQ, the eAects of ZP120 were not modified by 1 mM naloxone, but they were antagonized by the NOP receptor selective antagonist J-113397 (pA2 7.80 vs ZP120, 7.81 vs N/OFQ). 3 In vivo, ZP120 mimicked the eAects of N/OFQ, producing pronociceptive eAects in the tail withdrawal assay and decreased locomotor activity after i.c.v., but not after i.v. administration in mice. ZP120 elicited similar maximal eAects as N/OFQ, but it was about 10 fold more potent and its eAects lasted longer. 4 In conclusion, the novel NOP receptor ligand ZP120 is a highly potent and selective partial agonist of the NOP receptor with prolonged eAects in vivo.

Phe4 in the nociceptin (NC) sequence has been identified as the most critical residue for receptor interaction. In the present study, we investigated the pharmacological activity of a series of NC(1-13)NH2 analogues, in which the hydrogen atom in the para position of Phe4 was substituted with F, NO2, CN, Cl, Br, I, CH3, OH or NH2. In receptor binding studies, performed using CHO cells expressing the recombinant human NC receptor (CHOhOP4) and in rat cerebral cortex membranes, [(pF)Phe4]NC(1-13)NH2, [(pNO2)Phe4]NC(1-13)NH2, and [(pCN)Phe4]NC(1-13)NH2 displayed higher affinity than NC(1-13)NH2. The affinity of [(pCl)Phe4]NC(1-13)NH2 was essentially identical to that of NC(1-13)NH2, while the remaining compounds displayed reduced affinity. In a series of functional assays (stimulation of GTPγS binding in CHOhOP4 cells and rat cerebral cortex membranes and inhibition of cAMP accumulation in CHOhOP4 cells), the para substituted analogues behaved as full agonists (with the exception of [(pOH)Phe4]NC(1-13)NH2 which acted as a partial agonist in the GTPγS binding assays) with the following rank order potency: ${\rm pF = pNO}_{\rm 2} \ge {\rm pCN} \ge {\rm NC = NC(1 - 13)NH}_{\rm 2} {\rm = pCl} \ge {\rm pBr > pI = pCH}_{\rm 3} {\rm > pOH > pNH}_{\rm 2} $ [(pF)Phe4]NC(1-13)NH2 and [(pNO2)Phe4]NC(1-13)NH2 were either inactive or displayed micromolar potencies in cAMP accumulation experiments performed on cells expressing classical opioid receptors. All compounds were full agonists in isolated tissues from various species (guinea pig ileum, mouse colon and mouse/rat vas deferens) with the exception of [(pOH)Phe4]NC(1-13)NH2 which displayed partial agonist/weak antagonist activities. The rank order of potency was similar to that found in the other assays. The effects of all analogues were not modified by naloxone. The selective OP4 receptor antagonist [Nphe1]NC(1-13)NH2, tested in all preparations against one or both of the highly potent derivatives [(pF)Phe4]NC(1-13)NH2 and [(pNO2)Phe4]NC(1-13)NH2, showed pA2 values similar to those found against NC, the pA2 in the GTPγS binding/rat cerebral cortex assay being much higher (ca. 7.5) than in the other functional assays (ca. 6). This study further supports the notion that Phe4 of NC is the critical residue for receptor occupation and activation. Moreover, as part of this study, we have identified two novel, highly potent and selective agonists for the OP4 receptor, [(pF)Phe4]NC(1-13)NH2 and [(pNO2)Phe4]NC(1-13)NH2.

1. Nociceptin/orphanin FQ (N/OFQ) modulates several biological functions by activating a specific G-protein coupled receptor (NOP). Few molecules are available that selectively activate or block the NOP receptor. Here we describe the in vitro and in vivo pharmacological profile of a novel NOP receptor ligand, [Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-101). 2. UFP-101 binds to the human recombinant NOP receptor expressed in Chinese hamster ovary (CHO) cells with high affinity (pK(i) 10.2) and shows more than 3000 fold selectivity over classical opioid receptors. UFP-101 competitively antagonizes the effects of N/OFQ on GTPgamma(35)S binding in CHO(hNOP) cell membranes (pA(2) 9.1) and on cyclic AMP accumulation in CHO(hNOP) cells (pA(2) 7.1), being per se inactive at concentrations up to 10 microM. 3. In isolated peripheral tissues of mice, rats and guinea-pigs, and in rat cerebral cortex synaptosomes preloaded with [(3)H]-5-HT, UFP-101 competitively antagonized the effects of N/OFQ with pA(2) values in the range of 7.3 - 7.7. In the same preparations, the peptide was inactive alone and did not modify the effects of classical opioid receptor agonists. 4. UFP-101 is also active in vivo where it prevented the depressant action on locomotor activity and the pronociceptive effect induced by 1 nmol N/OFQ i.c.v. in the mouse. In the tail withdrawal assay, UFP-101 at 10 nmol produces per se a robust and long lasting antinociceptive effect. 5. UFP-101 is a novel, potent and selective NOP receptor antagonist which appears to be a useful tool for future investigations of the N/OFQ-NOP receptor system.

A total of 32 compounds was prepared to investigate the functional role of Phe(4) in NC(1-13)-NH(2), the minimal sequence maintaining the same activity as the natural peptide nociceptin. These compounds could be divided into three series in which Phe(4) was replaced with residues that would (i) alter aromaticity or side chain length, (ii) introduce steric constraint, and (iii) modify the phenyl ring. Compounds were tested for biological activity as (a) inhibitors of the electrically stimulated contraction of the mouse vas deferens; (b) competitors of the binding of [(3)H]-NC-NH(2) to mouse brain membranes; and (c) inhibitors of forskolin-stimulated cAMP accumulation in CHO cells expressing the recombinant human OP(4) receptor. Results indicate that all compounds of the first and second series were inactive or very weak with the exception of [N(CH(3))Phe(4)]NC(1-13)-NH(2), which was only 3-fold less potent than NC(1-13)-NH(2). Compounds of the third series showed higher, equal, or lower potencies than NC(1-13)-NH(2). In particular, [(pF)Phe(4)]NC(1-13)-NH(2) (pF) and [(pNO(2))Phe(4)]NC(1-13)-NH(2) (pNO(2)) were more active than NC(1-13)-NH(2) by a factor of 5. In the mVD, these compounds showed the following order of potency: (pF) = (pNO(2)) > or = (pCN) > (pCl) > (pBr) > (pI) = (pCF(3)) = (pOCH(3)) > (pCH(3)) > (pNH(2)) = (pOH). (oF) and especially (mF) maintained high potencies but were less active than (pF). Similar orders of potency were observed in binding competition and cAMP accumulation studies. There was a strong (r(2) > or = 0.66) correlation between data observed in these assays. Biological activity data of compounds of the third series were plotted against some Hansch parameters that are currently used to quantify physicochemical features of the substituents. In the three biological assays agonist potency/affinity positively correlates with the electron withdrawal properties of the groups in the p-position of Phe(4) and inversely with their size.

A series of analogs of the ORL1 receptor antagonist [Nphe1]-NC(1-13)-NH2 was prepared and tested for agonistic and antagonistic activities in the mouse vas deferens, a preparation that shows high sensitivity to nociceptin and related peptides. The purpose of this study was to determine the role of the aromatic residue at the N-terminal for antagonism and eventually identify compounds with improved potency. Results indicated that all 23 compounds are inactive as agonists, and the antagonistic potency of the initial template [Nphe1]-NC(1-13)-NH2 is high (pKB 6.43) compared with those of all other compounds except [(S)(betaMe)Nphe1]NC(1-13)-NH2 (pK(B) 6.48). The other 22 compounds can be divided into two groups: 10 show antagonistic potencies (pK(B)) ranging from 5.30 to 5.86, whereas the other 12 compounds are inactive. This study clearly shows that the aromatic ring of Nphe is very critical for the interaction with the ORL1 receptor and can not be enlarged or sterically modified without significant loss of antagonistic potency.

Peptide III-BTD has been recently identified as a non selective nociceptin/orphanin FQ receptor ligand by screening of a synthetic peptide combinatorial library. In the present study we evaluated the pharmacological profile of peptide III-BTD in isolated tissues (mouse and rat vas deferens, guinea pig ileum) sensitive to both nociceptin and opioid peptides. In the mouse vas deferens and guinea pig ileum, III-BTD concentration dependently inhibited the electrically induced twitch (pEC50 5.91 and 6.18, respectively; Emax 94 ± 1% and 94 ± 2%) and this effect was blocked by naloxone (1 μM). In the rat vas deferens, III-BTD was inactive in most of the tissues, while in few others it elicited a slight inhibition only at the highest concentration tested (10 μM). In the presence of 1 μM naloxone, 1 μM III-BTD shifted to the right the concentration response curve of nociceptin in a parallel manner, showing pKB values in the range 6.6–6.9. These data confirm on native nociceptin receptors the pharmacological profile of peptide III-BTD which behaved as a mixed nociceptin receptor antagonist / opioid receptor agonist in the [35S]GTPγS binding assay performed on cells expressing the recombinant human receptors.

Previous structure-activity studies on nociceptin/orphanin FQ (N/OFQ) identified [Phe(1)Psi(CH(2)NH)Gly(2)]N/OFQ(1-13)-NH(2) and [Nphe(1)]N/OFQ(1-13)-NH(2) as a N/OFQ peptide receptor (NOP) partial agonist and pure antagonist, respectively. The addition of fluorine to the Phe(4) or the insertion of a further pair of basic amino acids Arg(14)-Lys(15) generate potent agonists. On the basis of these findings, we combined in the N/OFQ-NH(2) template the chemical modifications Arg(14)-Lys(15) and (pF)Phe(4) that increase the agonist potency with those conferring partial agonist (Phe(1)Psi(CH(2)NH)Gly(2)) or pure antagonist (Nphe(1)) properties. Twelve peptides were synthesized and pharmacologically evaluated in Chinese hamster ovary cells expressing the human recombinant NOP and in electrically stimulated mouse vas deferens and guinea pig ileum assays. All peptides behaved as NOP ligands; the chemical modifications Arg(14)-Lys(15) and (pF)Phe(4) increased ligand affinity/potency. Peptides with the normal Phe(1)-Gly(2) peptide bond behaved as full agonists, and those with the Phe(1)Psi(CH(2)NH)Gly(2) modification behaved as partial agonists, while those with the Nphe(1) modification behaved as partial agonists or pure antagonists depending on the presence or absence of the (pF)Phe(4) modification, respectively. The full agonist [(pF)Phe(4),Arg(14),Lys(15)]N/OFQ-NH(2), the partial agonist [Phe(1)Psi(CH(2)NH)Gly(2),(pF)Phe(4),Arg(14),Lys(15)]N/OFQ-NH(2), and the pure antagonist [Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2) represent the most potent peptide ligands for NOP.

A novel ligand for the nociceptin/orphanin FQ (N/OFQ) receptor (NOP), [(pF)Phe(4),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-102), has been generated by combining in the N/OFQ-NH(2) sequence two chemical modifications, [Arg(14),Lys(15)] and [(pF)Phe(4)], that have been previously demonstrated to increase potency. In vitro, UFP-102 bound with high affinity to the human NOP receptor, showed at least 200-fold selectivity over classical opioid receptors, and mimicked N/OFQ effects in CHO(hNOP) cells, isolated tissues from various species, and mouse cortical synaptosomes releasing 5-hydroxytryptamine. UFP-102 showed similar maximal effects but higher potency (2- to 48-fold) relative to N/OFQ. The effects of UFP-102 were sensitive to NOP-selective antagonists J-113397 [(+/-)-trans-1-[1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one] (pA(2) = 7.75-8.12) and UFP-101 ([Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2))(pA(2) = 6.91-7.33) but not to naloxone, and no longer observed in tissues taken from NOP receptor knockout mice (NOP(-/-)). In vivo, UFP-102 (0.01-0.3 nmol i.c.v.) mimicked the pronociceptive action of N/OFQ (0.1-10 nmol i.c.v.) in the mouse tail withdrawal assay, displaying higher potency and longer lasting effects. The action of UFP-102 was not apparent in NOP(-/-) mice. Similar results were obtained measuring locomotor activity in mice. In conscious rats, UFP-102 (0.05 nmol i.c.v.) produced a marked and sustained decrease in heart rate, mean arterial pressure, and urinary sodium excretion and a profound increase in urine flow rate. These effects were comparable with those evoked by N/OFQ at 5 nmol. Collectively, these findings demonstrate that UFP-102 behaves as a highly potent and selective NOP receptor agonist that produces long-lasting effects in vivo.

Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the G-protein coupled receptor referred to as N/OFQ peptide (NOP) receptor. NOP receptor activation by N/OFQ modulates several biological functions both at central and peripheral level. Structure activity relationship (SAR) studies demonstrated that the N/OFQ sequence can be divided into a N-terminal tetrapeptide ‘message’ crucial for receptor activation and a C-terminal ‘address’ important for receptor binding. On the basis of this message/address concept we synthesized some chimeric compounds in which we substituted the natural message domain with the nonselective nonpeptide NOP ligand (8-Naphthalen-1-yl-methyl-4-oxo-1-phenyl-1,3,8-triaza-spiro[4,5]dec-3-yl)-aceticacid methyl ester (NNC 63-0532) and used as address domain the peptide sequences Thr-NH2, N/OFQ(5-9)-NH2, N/OFQ(5-13)-NH2 and N/OFQ(5-17)-NH2. All the compounds were pharmacologically evaluated in the electrically stimulated guinea-pig ileum. NNC 63-0532 produced a concentration-dependent inhibition of the electrically induced twitches showing, in comparison with N/OFQ, lower potency and higher maximal effects. In addition, contrary to N/OFQ, the effects of NNC 63-0532 were insensitive to the NOP selective antagonist [Nphe1, Arg14, Lys15]N/OFQ-NH2 (UFP-101) while prevented by naloxone. Similar results were obtained with NNC 63-0532/Thr-NH2 and NNC 63-0532/N/OFQ(1-9)-NH2. On the contrary, the inhibitory effects of NNC 63-0532/N/OFQ(5-13)-NH2 and NNC 63-0532/N/OFQ(5-17)-NH2 were slightly antagonized by UFP-101 while naloxone prevented the effects of the high but not of the low concentrations of the two ligands. These data indicate that it is possible to functionalize with the N/OFQ address sequence a nonpeptide NOP ligand for increasing its binding to the NOP receptor. Moreover, these results corroborate the idea that the 5–13 sequence represents the crucial core of the N/OFQ address domain.

UNLABELLED Complex regional pain syndrome is often treated with the sympatholytic guanethidine and a local anesthetic in a Bier's block. The efficacy of this treatment has been questioned. Because local anesthetics inhibit the norepinephrine uptake transporter, we hypothesized that this variable efficacy results from the local inhibiting the uptake of guanethidine. In this study, we tested this hypothesis by using a sympathetically innervated mouse vas deferens preparation. Organ bath-mounted mouse vasa deferentia were electrically stimulated in the absence and presence of guanethidine, prilocaine, procaine, and cocaine in various combinations. Prilocaine (1 mM) induced an immediate inhibition of twitch response (maximum 100% after 2 min) that fully reversed after washing. Guanethidine (3 microM) also inhibited twitching by 95% +/- 3% in 15 min, but this effect was only partially reversed after 1 h of washing (33% +/- 12% of control). When prilocaine and guanethidine were added in combination, a reversal of 80% +/- 13% (at 1 h) was observed. Procaine (300 micro M) produced a transient increase (152% +/- 14%) in response. When co-incubated with guanethidine (3 microM), the twitch was reduced to 24% +/- 4% of control and was reversed to 77% +/- 7% after 1 h. Cocaine (30 microM) inhibited the twitch response to 53% +/- 8%, which was fully reversed by 1 h of washing. When co-incubated with guanethidine, the response was reduced to 39% +/- 6% of control and was reversed to 86% +/- 10% after 1 h. In all cases, the reversal produced by the combination was significantly more intense (P < 0.05) than that produced by guanethidine alone. Local anesthetics reduce the sympatholytic actions of guanethidine, and this may explain the variable efficacy of guanethidine in the treatment of complex regional pain syndrome. IMPLICATIONS In this study, with a sympathetically innervated vas deferens preparation, local anesthetics reduced the efficacy of the sympatholytic guanethidine, questioning its co-administration in the pain clinic.

1 This study reports on the pharmacological characterization of ZP120, a novel ligand of the nociceptin/orphanin FQ (N/OFQ) peptide receptor, NOP. ZP120 is a structure inducing probes modified NOP ligand: Zealand Pharma proprietary SIP technology was used to increase the enzymatic stability and half-life of peptide. 2 In vitro, ZP120 mimicked the inhibitory effects of N/OFQ in the electrically stimulated mouse vas deferens, showing however higher potency (pEC(50) 8.88 vs 7.74), lower maximal effects (E(max) 69+/-5% vs 91+/-2%), and slower onset of action. Like N/OFQ, the effects of ZP120 were not modified by 1 micro M naloxone, but they were antagonized by the NOP receptor selective antagonist J-113397 (pA(2) 7.80 vs ZP120, 7.81 vs N/OFQ). 3 In vivo, ZP120 mimicked the effects of N/OFQ, producing pronociceptive effects in the tail withdrawal assay and decreased locomotor activity after i.c.v., but not after i.v. administration in mice. ZP120 elicited similar maximal effects as N/OFQ, but it was about 10 fold more potent and its effects lasted longer. 4 In conclusion, the novel NOP receptor ligand ZP120 is a highly potent and selective partial agonist of the NOP receptor with prolonged effects in vivo.

Phe(4) in the nociceptin (NC) sequence has been identified as the most critical residue for receptor interaction. In the present study, we investigated the pharmacological activity of a series of NC(1-13)NH(2) analogues, in which the hydrogen atom in the para position of Phe(4) was substituted with F, NO(2), CN, Cl, Br, I, CH(3), OH or NH(2). In receptor binding studies, performed using CHO cells expressing the recombinant human NC receptor (CHO(hOP4)) and in rat cerebral cortex membranes, [(pF)Phe(4)]NC(1-13)NH(2), [(pNO(2))Phe(4)]NC(1-13)NH(2), and [(pCN)Phe(4)]NC(1-13)NH(2) displayed higher affinity than NC(1-13)NH(2). The affinity of [(pCl)Phe(4)]NC(1-13)NH(2) was essentially identical to that of NC(1-13)NH(2), while the remaining compounds displayed reduced affinity. In a series of functional assays (stimulation of GTPgammaS binding in CHO(hOP4)cells and rat cerebral cortex membranes and inhibition of cAMP accumulation in CHO(hOP4) cells), the para substituted analogues behaved as full agonists (with the exception of [(pOH)Phe(4)]NC(1-13)NH(2) which acted as a partial agonist in the GTPgammaS binding assays) with the following rank order potency:[(pF)Phe(4)]NC(1-13)NH(2) and [(pNO(2))Phe(4)]NC(1-13)NH(2) were either inactive or displayed micromolar potencies in cAMP accumulation experiments performed on cells expressing classical opioid receptors. All compounds were full agonists in isolated tissues from various species (guinea pig ileum, mouse colon and mouse/rat vas deferens) with the exception of [(pOH)Phe(4)]NC(1-13)NH(2) which displayed partial agonist/weak antagonist activities. The rank order of potency was similar to that found in the other assays. The effects of all analogues were not modified by naloxone. The selective OP(4) receptor antagonist [Nphe(1)]NC(1-13)NH(2), tested in all preparations against one or both of the highly potent derivatives [(pF)Phe(4)]NC(1-13)NH(2) and [(pNO(2))Phe(4)]NC(1-13)NH(2), showed pA(2) values similar to those found against NC, the pA(2) in the GTPgammaS binding/rat cerebral cortex assay being much higher (ca. 7.5) than in the other functional assays (ca. 6). This study further supports the notion that Phe(4) of NC is the critical residue for receptor occupation and activation. Moreover, as part of this study, we have identified two novel, highly potent and selective agonists for the OP(4) receptor, [(pF)Phe(4)]NC(1-13)NH(2) and [(pNO(2))Phe(4)]NC(1-13)NH(2).

Nociceptin (NC)/orphanin FQ (H-Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-Arg-Lys-Leu-Ala-Asn-Gln-OH) is a neuropeptide, which modulates several biological functions by activating the ORL1 receptor [1]. In the past years, we have performed systematic structure activity studies on NC that have established: a) NC residues 1–13 are sufficient both for high ORL1 receptor binding and biological activity; b) The basic residues in the C-terminal sequence, especially Arg8, appear to be instrumental for ORL1 receptor recognition; c) Contrary to opioid peptides, which strictly require Tyrfor opioid receptor activation, the active core of NC that stimulates the ORL1 receptor, is the Phe4; d) Specific changes of the N-terminal sequence, expecially at Phe, led to the discovery of a partial agonist, [PheΨ(CH2-NH)Gly2]NC(1–13)-NH2, and [Nphe]NC(1–13)-NH2, a pure antagonist of the ORL1 receptor [2]. In the present investigation, we describe the effect of substitutions with a halogen series of the Phe4aromatic side chain of the NC(1–13)-NH2, and identification of new ligands, which behave as superagonists of the ORL1 receptor.

Several synthetic peptides containing L-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (L-Tic) in the second position show δ-selective opioid antagonist activity [1]. We have reported that enhancement of δ-opioid antagonist potency was achieved by synthetic di- and tri-peptides in which Tyr1 was substituted by 2,6-dimethyl-L- tyrosine (Dmt) [2]. Recently, Schiller et al. [3] reported the development of novel δ opioid agonists structurally derived from the prototype δ antagonist TIPP (H-Tyr-Tic-Phe-Phe-OH). In the present investigation, we modified the selective δ antagonist Dmt-Tic, and identified highly potent δ opioid agonists and δ opioid antagonists/µ agonists.

This chapter aims to further the conceptual clarity of co-creation, by classifying and exploring the spectrum of non-government actor–led governance arrangements for the co-creation of nature-based solutions (NBS) across different European contexts. Case studies from pilot demonstrators in current Horizon 2020 projects (proGIreg, CLEVER Cities, and EdiCitNet in Italy, Germany, the Netherlands, and the United Kingdom) are used to illustrate collaborative governance arrangements within the operating space of co-creation, delineate respective actor roles, and identify lessons learnt.

A presente tese considera dois dos grandes desafios globais da atualidade: a emergência climática e a perda de biodiversidade. Por serem problemas extremamente complexos e interrelacionados a diferentes origens, temáticas e áreas do conhecimento, apresentam distintas formas de serem analisados e endereçados. A busca por ações pelo clima e pela biodiversidade, a fim de tentar minimamente estancar ou reverter as tendências mais pessimistas apontadas pela ciência, é algo imperativo. A partir de meados da década de 2010, o conceito de Soluções baseadas na Natureza (SbN) começa a ser disseminado e apresenta-se como uma das possíveis abordagens para endereçar desafios sociais, econômicos e ambientais, incluindo aspectos da mudança do clima, e que garantam benefícios diretos para a biodiversidade. A vertente de adaptação às mudanças do clima tem ganhado importância diante da concretude dos riscos climáticos, porém precisa ser otimizada e aprimorada, a fim de reduzir os potenciais impactos negativos. Muitas medidas de adaptação, em sua maioria, ainda são vistas como soluções de engenharia ou tecnológicas, mas há um crescente reconhecimento da importância de medidas sociais, institucionais e inspiradas na natureza. Diante dos cenários de incerteza climática, enfatiza-se cada vez mais a necessidade da busca por soluções mais flexíveis, multifuncionais e contempladas em processos mais amplos de aprendizagem e tecnologias sociais. No contexto brasileiro, os municípios que se aproximam dessas temáticas o fazem por diferentes formas e por distintas motivações. A pesquisa pretende apresentar possíveis contribuições para o planejamento e implementação de Soluções baseadas na Natureza (SbN) no contexto brasileiro, que possam também apoiar no enfrentamento e adaptação à mudança do clima, a partir da sistematização e análise das experiências de Campinas (SP) e Recife (PE). A tese é composta por seis capítulos e suas respectivas subseções. Abrange conceitos gerais de mitigação e adaptação à mudança do clima, da perda da biodiversidade e degradação dos serviços ecossistêmicos, princípios relacionados às SbN e como esses tópicos são endereçados no Brasil, atualmente. A partir do referencial teórico, da definição dos estudos de caso, da observação e pesquisa participante e de entrevistas semiestruturadas com especialistas e representantes dos dois municípios, foram feitas observações em relação aos ciclos de políticas públicas na escala local, principalmente no que se refere às etapas de formulação e planejamento para implementação. Para um olhar mais analítico, foi proposta uma primeira camada de aspectos comuns e fundamentais à maioria das políticas públicas, sendo eles os aspectos políticos, técnicos, sociais e financeiros. No âmbito de cada um desses quatro aspectos, foram identificados e estimados fatores que inibem o avanço da temática, que são barreiras (Fatores Inibidores) ou que podem apoiar e incentivar os avanços no respectivo contexto municipal (Fatores Propulsores). Os resultados indicam fatores que podem ser favoráveis ao avanço das agendas, ou que representam um desafio que precisa ser superado ou são um ponto de atenção que mereça ser observado no contexto municipal. Com isso, pretende-se que essas recomendações possam apoiar uma maior robustez e efetividade dos processos de planejamento e implementação a nível municipal, e possam reforçar alguns dos princípios e critérios relacionados ao conceito de SbN. This thesis considers two of the greatest current global challenges: the climate emergency and the loss of biodiversity. Since those are extremely complex problems interrelated to different causes, themes, and knowledge areas, they present distinct ways of being analyzed and addressed. The search climate and biodiversity actions, in order to minimally staunch or revert the most pessimist tendencies indicated by science, is imperative. After the mid-2010s, the concept of Nature-based Solutions (NbS) begins to be disclosed and is presented as one of the possible approaches to address social, economic, and environmental challenges, including aspects of climate change, and guaranteeing direct benefits for biodiversity. The adaptation to climate change dimension has been gaining significance in face of the materiality of climate risks, but it needs to be optimized and improved to reduce potential negative impacts. Most of the adaptation measures are still seen as engineering or technological solutions, but there is a growing recognition of the importance of social, institutional, and nature-inspired measures. Given the climate uncertainty scenarios, the need for solutions that are more flexible, multifunctional, and covered by broader learning and social technology processes is emphasized. In the Brazilian context, municipalities that approach these themes do so using different forms and motivations. This research aims to present possible contributions for planning and implementing Nature-based Solutions (NbS) in the Brazilian context, which can also support in coping and adapting to climate change, based on the systematization and analysis of the Campinas (SP) and Recife (PE) experiences. This thesis is composed by six chapters and its respective subsections. It covers general concepts of mitigation and adaptation to climate change, loss of biodiversity, and degradation of ecosystem services, principles related to NbS and how these topics are currently addressed in Brazil. Based on the theoretical references, on the definition of the case studies, on participative observations and research, and on semi-structured interview with specialists and representatives from both municipalities, observations were drawn in relation to the cycles of public policies in local scale, especially regarding the phases of formulation and planning for implementation. To cast a more analytical look, a first layer of aspects that are common and essential to most public policies was proposed, namely: the political, technical, social, and financial aspects. Within the scope of each of these four aspects, it was identified factors that constrain the advancement of the theme, which are barriers (Constrain Factors) or that may support and encourage advances in their respective municipal contexts (Enabling Factors). The results indicate factors that can be favorable to the advancement of the agendas, or that pose a challenge that needs to be overcome or are a point of attention that needs to be observed in the municipal context. With that, these recommendations are intended to support more robust and effective municipal planning and implementation processes and to reinforce some principles and criteria related to the NbS concept.

Presenze russe al Teatro alla Scala di Milano nella prima metà del Novecento.

G.L. Vakevič (1907-1984) - Dal 1921 è vissuto in Francia. Scenografo e costumista di fama internazionale in spettacoli d'opera, balletto, prosa e cinema, collabora a più di 200 opere liriche e 300 spettacoli teatrali, lavorando per teatri famosi come il Théâtre du Vieux Colombier e la Comédie Française a Parigi, la Royal Opera House del Covent Garden a Londra, il Festival di Salisburgo e la Scala di Milano, dove allestisce numerosi spettacoli negli anni Cinquanta e nei primi anni Sessanta.Nel 1982 gli è stato conferito il titolo di Accademico di Francia nella sezione pittura.

Elena Aleksandrovna Benois (1898-1972): pittrice, scenografa. Dal 1926 si trasferisce a Parigi. Partecipa insieme al padre e al fratello Nikolaj alla "Mostra dei Benois" organizzata nel 1955 a Villa Olmo a Como.

E. Ždanovskij (1892-1949) - cantante d'opera. Nel 1924 lascia la Russia. Si esibisce al Teatro Reale di Madrid e poi al Teatro alla Scala di Milano fino al 1941, dove riveste ruoli di basso in diverse opere. Si esibisce in diversi teatri italiani.

P.P. Muratov (1881-1950) - scrittore e storico dell'arte. Emigra nel 1923. Dal 1923 al 1927 vive a Roma e poi si trasferisce a Parigi. Autore dei tre volumi Immagini d'Italia.