Investigating alkyl nitrates as nitric oxide releasing precursors of multitarget acetylcholinesterase-monoamine oxidase B inhibitors

Herein we envisaged the possibility of exploiting alkyl nitrates as precursors of alcohol-bearing dual inhibitors targeting acetylcholinesterase (AChE) and monoamine oxidase B (MAO B), key enzymes in neurodegenerative syndromes such as Alzheimer's disease (AD), through biotransformation unmasking an alcoholic function upon nitric oxide (NO) release. The cooperation to neuroprotection of low fluxes of NO and target enzymes’ inhibition by the alcohol metabolites might return a multitargeting effect. The in vitro screening towards ChEs and MAOs of a collection of 21 primary alcohols disclosed a subset of dual inhibitors, among which three diverse chemotypes were selected to study the corresponding nitrates. Nitrate 14 proved to be a brain permeant, potent AChE-MAO B inhibitor by itself. Moreover, it protected human SH-SY5Y lines against rotenone and hydrogen peroxide with a poor inherent cytotoxicity and showed a slow conversion profile to its alcohol metabolite 9d that still behaved as bimodal and neuroprotective molecule

Five Years of Experimental Warming Increases the Biodiversity and Productivity of Phytoplankton

Phytoplankton are key components of aquatic ecosystems, fixing CO2 from the atmosphere through photosynthesis and supporting secondary production, yet relatively little is known about how future global warming might alter their biodiversity and associated ecosystem functioning. Here, we explore how the structure, function, and biodiversity of a planktonic metacommunity was altered after five years of experimental warming. Our outdoor mesocosm experiment was open to natural dispersal from the regional species pool, allowing us to explore the effects of experimental warming in the context of metacommunity dynamics. Warming of 4°C led to a 67% increase in the species richness of the phytoplankton, more evenly-distributed abundance, and higher rates of gross primary productivity. Warming elevated productivity indirectly, by increasing the biodiversity and biomass of the local phytoplankton communities. Warming also systematically shifted the taxonomic and functional trait composition of the phytoplankton, favoring large, colonial, inedible phytoplankton taxa, suggesting stronger top-down control, mediated by zooplankton grazing played an important role. Overall, our findings suggest that temperature can modulate species coexistence, and through such mechanisms, global warming could, in some cases, increase the species richness and productivity of phytoplankton communities

Enantiomeric Separation and Molecular Modelling of Bioactive 4-Aryl-3,4-dihydropyrimidin-2(1H)-one Ester Derivatives on Teicoplanin-Based Chiral Stationary Phase

The enantiomeric separation of 15 racemic 4-aryl-3,4-dihydropyrimidin-2(1H)-one (DHP) alkoxycarbonyl esters, some of which proved to be highly active as A2B adenosine receptor antagonists, was carried out by HPLC on ChirobioticTM TAG, a chiral stationary phase (CSP) bearing teicoplanin aglycone (TAG) as the chiral selector. The racemic compounds were separated under polar organic (PO) conditions. Preliminarily, the same selectands were investigated on three different Pirkle-type CSPs in normal-phase (NP) conditions. A baseline separation was successfully obtained on TAG-based CSPs for the majority of compounds, some of which achieved high enantioselectivity ratios ( > 2) in contrast with the smaller values (1–1.5) and the lack of baseline resolution observed with the Pirkle-type CSPs. In particular, the racemic tetrazole-fused DHP ester derivatives, namely compounds 8 and 9, were separated on TAG-based HPLC columns with noteworthy values (8.8 and 6.0, respectively), demonstrating the potential of the method for preparative purposes. A competition experiment, carried out with a racemic analyte (6) by adding N-acetyl-D-alanine (NADA) to the mobile phase, suggested that H-bonding interactions involved in the recognition of the natural dipeptide ligand D-Ala-D-Ala into the TAG cleft should be critical for enantioselective recognition of 4-aryl DHPs by TAG. The X-ray crystal structure of TAG was elucidated at a 0.77 Å resolution, whereas the calculation of molecular descriptors of size, polar, and H-bond interactions, were complemented with molecular docking and molecular dynamics calculations, shedding light on repulsive (steric effects) and attractive (H-bond—polar and apolar) interactions between 4-aryl DHP selectands and TAG chiral selectors

Roma: Oltre le baraccopoli: Agenda politica per ripartire dalle periferie dimenticate

Con il presente documento, presentato in vista delle elezioni comunali che si svolgeranno a Roma nel 2016, l’Associazione 21 luglio vuole proporre alle forze politiche e ai candidati a cariche elettive i principi essenziali per mutare radicalmente le politiche verso gli abitanti delle baraccopoli e dei micro insediamenti presenti nella Capitale. Le azioni previste nel documento hanno come obiettivo, nell’arco temporale di 5 anni: la chiusura graduale e progressiva delle baraccopoli e dei micro insediamenti della Capitale e il superamento dei centri di raccolta dove sono concentrate le famiglie vittime degli sgomberi che nel passato hanno coinvolto abitanti di numerose baraccopoli. “Roma: oltre le baraccopoli” si avvale degli studi condotti dall’Associazione 21 luglio e, nell’ultima parte, del prezioso apporto del prof. Tommaso Vitale, Sciences Po (Université Sorbonne Paris Cité)1. Il testo condivide medesimi principi e metodi riportati all’interno della “Delibera di iniziativa popolare per il superamento dei campi rom”, promossa da nove associazioni2 e sottoscritta da oltre 6.000 cittadini, depositata in Campidoglio l’11 settembre 2015

Évaluation de l’état écologique des plans d’eau aquitains à partir des communautés de producteurs primaires

En raison de leur importante capacité de réponse aux changements environnementaux, les producteurs primaires sont depuis longtemps utilisés comme indicateurs biologiques de la qualité des milieux aquatiques. La Directive Cadre Européenne sur l’Eau (2000/60/CE) préconise ainsi l’utilisation du phytoplancton, du phytobenthos et des macrophytes afin de mesurer l’état écologique des écosystèmes lacustres. Dans cette étude, ces trois compartiments ont été utilisés pour déterminer l’état écologique de cinq lacs localisés dans la région Aquitaine (Sud-Ouest de la France), lacs ayant la particularité de présenter des niveaux trophiques différents. Les résultats ont montré qu’au niveau intra-lac la composition floristique dépend fortement des variables physiques dans la plupart des systèmes tandis qu’au niveau inter-lac celle-ci dépend du niveau trophique. Le phytoplancton s’est révélé être l’indicateur de qualité le plus performant et le seul utilisable dans les eaux ouvertes, et le plus précis dans les systèmes où les macrophytes submergés étaient absents. Cependant, dans les lacs humiques, les assemblages phytoplanctoniques semblent répondre davantage à la turbidité et aux brassages fréquents de la colonne d’eau qu’aux nutriments. Dans de telles conditions, afin de mieux caractériser la qualité de l’eau, l’utilisation complémentaire du phytobenthos et des macrophytes se révèle plus pertinente. En conclusion, considérant les trois compartiments biologiques, la présente étude permet une approche complémentaire de l’état écologique des systèmes lacustres. Certaines des méthodes appliquées ici représentent un outil potentiel de détermination de la qualité de l’eau selon les exigences de la DCE, mais elles nécessitent d’être affinées pour une meilleure évaluation de l’état écologique des lacs français. Une attention particulière a été portée aux taxa exotiques observés dans ces lacs tempérés, et cet aspect doit être pris en considération lors de l’évaluation écologique. En effet, ces espèces sensiblement avantagées par les conséquences du changement climatique, peuvent altérer la structure et le fonctionnement des écosystèmes aquatiques en place, et aboutir à une perte de diversité.Due to their important ability to respond to environmental changes, primary producers have been used for a long time as biological indicators of water quality. The Water Framework Directive (2000/60/EC) recommends the use of the phytoplankton, phytobenthos (diatoms) and macrophytes in the ecological status assessment of lakes. In this study, these three compartments have been used to determine the ecological status of five lakes located in the Aquitaine region (southwest of France) with different trophic status. The results showed that within lakes, the floristic composition in most of the systems strongly depends on physical parameters whereas among lakes it depends on the trophic status. The phytoplankton proved to be the most powerful indicator of quality in open-water areas as well as in systems where submerged macrophytes are absent. However, in the humic lakes, the phytoplankton assemblages seem to respond more to turbidity and mixing than to nutrient load. Under such conditions, water quality could be underestimated and the complementary use of phytobenthos and macrophytes appears more appropriated. In conclusion, considering the three biological elements, the present study allows a complementary approach of the ecological status of the lakes. Some of the methods applied here represent a potential tool for the assessment of the ecological status in the context of WFD, but they need to be refined to assess more properly the ecological status of French lakes. A special attention was paid to exotic taxa observed in these temperate lakes, and this aspect must be taken into account in the ecological assessment. Indeed, these species favoured by the consequences of the climate change, can modify the structure and functioning of the aquatic ecosystems, and lead to a loss of diversity

Ecological status assessment of Aquitaine lakes using primary producer communities

En raison de leur importante capacité de réponse aux changements environnementaux, les producteurs primaires sont depuis longtemps utilisés comme indicateurs biologiques de la qualité des milieux aquatiques. La Directive Cadre Européenne sur l'Eau (DCE) préconise ainsi, de 2000, l'utilisation du phytoplancton, du phytobenthos et des macrophytes afin de mesurer l'état écologique des écosystèmes lacustres. Dans cette étude, ces trois compartiments ont été utilisés pour déterminer l'état écologique de cinq lacs localisés dans la région Aquitaine (Sud-Ouest de la France), lacs ayant la particularité de présenter des niveaux trophiques différents. Les résultats ont montré qu'au niveau intra-lac la composition floristique dépend fortement des variables physiques dans la plupart des systèmes tandis qu'au niveau inter-lac celle-ci dépend du niveau trophique. Le phytoplancton s'est révélé être l'indicateur de qualité le plus performant dans les eaux ouvertes, ainsi que dans les systèmes où les macrophytes submergés étaient absents. Cependant, dans les lacs humiques, les assemblages phytoplanctoniques semblent répondre davantage à la turbidité et aux brassages fréquents de la colonne d'eau qu'aux nutriments. Dans de telles conditions, afin de mieux caractériser la qualité de l'eau, l'utilisation complémentaire du phytobenthos et des macrophytes se révèle plus pertinente.En conclusion, considérant les trois éléments biologiques, la présente étude permet une approche intégrée de l'état écologique du système. Certaines des méthodes appliquées ici représentent un outil potentiel de détermination de la qualité de l'eau selon les exigences de la DCE, mais elles nécessitent d'être affinées pour une meilleure évaluation de l'état écologique des lacs français. Une attention particulière a été portée aux taxa exotiques observés dans ces lacs tempérés, et cet aspect doit être pris en considération lors de l'évaluation écologique. En effet, ces espèces sensiblement avantagées par les conséquences du changement climatique, peuvent altérer la structure et le fonctionnement des écosystèmes aquatiques en place, et aboutir à une perte de diversité.Due to their important ability to respond to environmental changes, primary producers have been used for a long time as biological indicators of water quality. The Water Framework Directive (WFD) in 2000 recommends the use of the phytoplankton, phytobenthos (diatoms) and macrophytes in the ecological status assessment of lakes. In this study, these three compartments have been used to determine the ecological status of five lakes located in the Aquitaine region (southwest of France) with different trophic status. The results showed that within lakes, the floristic composition in most of the systems strongly depends on physical parameters whereas among lakes it depends on the trophic status. The phytoplankton proved to be the most powerful indicator of quality in open-water areas as well as in systems where submerged macrophytes are absent. However, in the humic lakes, the phytoplankton assemblages seem to respond more to turbidity and mixing than to nutrient load. Under such conditions, water quality could be underestimated and the complementary use of phytobenthos and macrophytes appears more appropriated.In conclusion, considering the three biological elements, the present study allows an integrated approach of the ecological status of the system. Some of the methods applied here represent a potential tool for the assessment of the ecological status in the context of WFD, but they need to be refined to assess more properly the ecological status of French lakes. A special attention was paid to exotic taxa observed in these temperate lakes, and this aspect must be taken into account in the ecological assessment. Indeed, these species favoured by the consequences of the climate change, can modify the structure and functioning of the aquatic ecosystems, and lead to a loss of diversity

Forme di autorganizzazione sociale nelle periferie urbane e sul territorio

In vari contesti urbani, rurali e montani si sono diffuse sia pratiche molecolari sia forme di autorganizzazione socio-territoriale che rispondono ad esigenze e situazioni differenti spesso compresenti e complementari: il desiderio e la capacità di riappropriarsi dello spazio di vita ma anche di alcune dinamiche di sviluppo e gestione del territorio; l’obiettivo di superamento dell’inerzia della pubblica amministrazione in un contesto di progressivo allontanamento della politica e delle istituzioni dai territori; la necessità di rispondere ad esigenze urbane e sociali (servizi, spazi verdi, spazi pubblici, attrezzature, ecc.) che sempre meno sono disponibili soprattutto in forza del forte arretramento del welfare state; il desiderio e l’obiettivo di recuperare una dimensione di qualità (e, nei contesti urbani, di urbanità) che il modello di sviluppo neoliberista sta cancellando, reclamando così una diversa idea di città e di territorio.In various urban, rural and mountain contexts, both molecular practices and forms of socio-territorial self-organization that respond to different needs and situations that are often present and complementary have spread: the desire and the ability to regain the living space but also some dynamics of territory development and management; the goal of overcoming the inertia of the public administration in a context of progressive removal of politics and institutions from the territories; the need to respond to urban and social needs (services, green spaces, public spaces, equipment, etc.) which are increasingly available mainly due to the strong retreat of the welfare state; the desire and the goal of recovering a quality dimension (and, in urban contexts, of urbanity) that the neoliberal development model is canceling, thus claiming a different idea of city and territory