Enea è uno studente italiano. Nuove generazioni e cittadinanza

What ‘bridges’ there are between the first generations who immigrated to Italy from many different countries and the second or third generations born and raised in Italy? Along with the difficulties, and sometimes the suffering of the “lives in between” there are also positive aspects: the new generations of immigrants look like all the new generations but are more cosmopolitan and more “naturally” intercultural be-cause they are used to seeking a balance between different worlds. They are girls and boys who are indeed Italians, but still without citizenship. They know more languages than their Italian peers and achieve better results in learning English, as shown by the annual Invalsi surveys. They are projected towards the culture of the country in which they live. “Natural equilibrists”, they can teach us something about what it means to grow up managing similarities and differences. They can tell us about a new idea of citizenship.Che “ponti” ci sono tra le prime generazioni immigrate in Italia da tanti e diversi Paesi e le seconde generazioni, o le terze, nate e cresciute in Italia? Insieme alle dif-ficoltà, e a volte alle sofferenze delle “vite in mezzo” ci sono anche aspetti positivi: le nuove generazioni dell'immigrazione assomigliano a tutte le nuove generazioni ma sono più cosmopolite e più “naturalmente” interculturali perché abituate a cercare un equilibrio tra mondi diversi. Sono ragazze e ragazzi italiani di fatto, ma ancora privi di cittadinanza formale. Conoscono più lingue dei coetanei italiani, ottengono risultati migliori nell'apprendimento della lingua inglese, come dimostrano le rilevazioni annuali Invalsi. Sono proiettate verso la cultura del paese in cui vivono. “Equlibristi naturali”, possono insegnarci qualcosa su cosa significhi crescere gestendo somiglianze e differenze. Possono raccontarci un’idea nuova di cittadinanza

2-Benz­yloxy-1,2,4-triazolo[1,5-a]quinazolin-5(4H)-one

The title compound, C16H12N4O2, is a functionalized triazoloquinazoline with a substituted benz­yloxy group attached at the 2-position of a triazole spacer. The triazoloquinazoline fused-ring system is approximately planar (r.m.s. deviation = 0.016 Å) while the benzyl substituent is perpendicular to the ring system, making a dihedral angle of 65.29 (6)°. The phenyl ring of the benz­yloxy moiety is equally disordered over two sets of sites. A centrosymmetric N—H⋯N hydrogen bond connects mol­ecules into dimers

Patrimonio Natural y Cultural de Punta Cuevas Educar para la Conservación

ResumenEl presente trabajo es una experiencia didácticatransdisciplinaria realizada en la ciudad de PuertoMadryn por estudiantes y docentes de la EscuelaSecundaria de Educación Técnico ProfesionalN° 728 “Alfonsina Storni”. La misma consistióen una salida educativa al Parque Histórico PuntaCuevas con la finalidad de brindar herramientas através de la educación e interpretación ambiental,para que los estudiantes puedan comprenderla compleja estructura del ambiente, formándoseen una concepción holística donde se evidenciela interacción de los aspectos físicos, biológicos,sociales y culturales del lugar para la preservacióndel patrimonio natural y cultural. Natural and Cultural Heritage of Punta CuevasEducating for Conservation AbstractThis work is based on a transdisciplinary didacticexperience carried out in Puerto Madryn, bystudents and teachers of the 728 “AlfonsinaStorni” highschool of technical-professionaleducation. It consisted of an educational fieldtrip to the historical park Punta Cuevas withthe objective of providing, through the use ofconservation education and interpretation, anunderstanding of the complex structure of theenvironment, forming a broad conceptualisationwhere the interactions between the physical,biological, social and cultural aspects of the placeis evident, so as to promote the preservation ofthe natural and cultural heritage of the region

Persistent behavioral sensitization to chronic L-DOPA requires A2A adenosine receptors

To investigate the role of A2A adenosine receptors in adaptive responses to chronic intermittent dopamine receptor stimulation, we compared the behavioral sensitization elicited by repeated L-DOPA treatment in hemiparkinsonian wild-type (WT) and A2A adenosine receptor knock-out (A2A KO) mice. Although the unilateral nigrostriatal lesion produced by intrastriatal injection of 6-hydroxydopamine was indistinguishable between WT and A2A KO mice, they developed strikingly different patterns of behavioral sensitization after daily treatment with low doses of L-DOPA for 3 weeks. WT mice initially displayed modest contralateral rotational responses and then developed progressively greater responses that reached a maximum within 1 week and persisted for the duration of the treatment. In contrast, any rotational behavioral sensitization in A2A KO mice was transient and completely reversed within 2 weeks. Similarly, the time to reach the peak rotation was progressively shortened in WT mice but remained unchanged in A2A KO mice. Furthermore, daily L-DOPA treatment produced gradually sensitized grooming in WT mice but failed to induce any sensitized grooming in A2A KO mice. Finally, repeated L-DOPA treatment reversed the 6-OHDA-induced reduction of striatal dynorphin mRNA in WT but not A2A KO mice, raising the possibility that the A2A receptor may contribute to L-DOPA-induced behavioral sensitization by facilitating adaptations within the dynorphin-expressing striatonigral pathway. Together these results demonstrate that the A2A receptor plays a critical role in the development and particularly the persistence of behavioral sensitization to repeated L-DOPA treatment. Furthermore, they raise the possibility that the maladaptive dyskinetic responses to chronic L-DOPA treatment in Parkinson's disease may be attenuated by A2A receptor inactivation.Peer Reviewe

Bioactive and Elastic Emulsion Electrospun DegraPol Tubes Delivering IGF-1 for Tendon Rupture Repair

Tendon injuries can result in two major drawbacks. Adhesions to the surrounding tissue may limit the range of motion, while fibrovascular scar formation can lead to poor biomechanical outcomes. Prosthetic devices may help to mitigate those problems. Emulsion electrospinning was used to develop a novel three-layer tube based on the polymer DegraPol (DP), with incorporated insulin-like growth factor-1 (IGF-1) in the middle layer. Scanning electron microscopy was utilized to assess the fiber diameter in IGF-1 containing pure DP meshes. Further characterization was performed with Fourier Transformed Infrared Spectroscopy, Differential Scanning Calorimetry, and water contact angle, as well as through the assessment of mechanical properties and release kinetics from ELISA, and the bioactivity of IGF-1 by qPCR of collagen I, ki67, and tenomodulin in rabbit Achilles tenocytes. The IGF-1-containing tubes exhibited a sustained release of the growth factor up to 4 days and showed bioactivity by significantly upregulated ki67 and tenomodulin gene expression. Moreover, they proved to be mechanically superior to pure DP tubes (significantly higher fracture strain, failure stress, and elastic modulus). The novel three-layer tubes intended to be applied over conventionally sutured tendons after a rupture may help accelerate the healing process. The release of IGF-1 stimulates proliferation and matrix synthesis of cells at the repair site. In addition, adhesion formation to surrounding tissue can be reduced due to the physical barrier

Gastric tolerability and prolonged prostaglandin inhibition in the brain with a nitric oxide-releasing flurbiprofen derivative (NCX 2216, [3-[4-(2-fluoro-a-methyl[1,1-biphenyl]-4-acetyloxy)-3-methoxyphenyl]-2-propenoic acid 4-nitrooxybutyl

ABSTRACT NCX-2216 [3-[4-(2-fluoro-␣-methyl-[1,1Ј-biphenyl]-4-acetyloxy)-3-methoxyphenyl]-2-propenoic acid 4-nitrooxy butyl ester] is an NO-releasing flurbiprofen derivative that also contains a ferulic acid (antioxidant) moiety. NCX-2216 has been shown to be effective in reducing ␤-amyloid deposition in a transgenic mouse model of Alzheimer's disease. The tolerability of this compound in the stomach and its ability to suppress prostaglandin synthesis in the brain are not known. The purpose of this study was to assess the contribution of nitric oxide (NO) and ferulic acid to the pharmacological properties of NCX-2216 versus flurbiprofen; thus, we compared their gastric tolerability and suppression of prostaglandin synthesis, peripherally and centrally. Oral flurbiprofen produced extensive gastric damage and suppressed gastric prostaglandin synthesis. In contrast, while suppressing prostaglandin production, equimolar doses of NCX-2216 did not cause detectable gastric injury. The NO-releasing moiety of NCX-2216 (but not the ferulic acid moiety) was crucial for the gastric safety of this compound. NCX-2216 substantially inhibited prostanoid synthesis despite not being detectable in plasma and despite producing only low amounts of flurbiprofen in plasma and in the brain. Inhibition of brain prostaglandin synthesis by NCX-2216 (22 mg/ kg) persisted for a much longer period of time (up to 48 h) than was seen with flurbiprofen (Յ12 h). These results demonstrate that a single administration of NCX-2216 can produce prolonged suppression of brain prostaglandin synthesis without causing gastric injury. It is likely that an active metabolite of NCX-2216 contributes to the suppression of cyclooxygenase activity. NCX-2216 may represent an attractive alternative to conventional nonsteroidal anti-inflammatory drugs for long-term treatment of a variety of inflammatory disorders, especially those occurring in the central nervous system

An aging Interventions Testing Program: study design and interim report

The National Institute on Aging's Interventions Testing Program (ITP) has developed a plan to evaluate agents that are considered plausible candidates for delaying rates of aging. Key features include: (i) use of genetically heterogeneous mice (a standardized four-way cross), (ii) replication at three test sites (the Jackson Laboratory, TJL; University of Michigan, UM; and University of Texas, UT), (iii) sufficient statistical power to detect 10 changes in lifespan, (iv) tests for age-dependent changes in T cell subsets and physical activity, and (v) an annual solicitation for collaborators who wish to suggest new interventions for evaluation. Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen (NFP), 4-OH- -phenyl-N-tert-butyl nitrone (4-OH-PBN), or nordihydroguiaretic acid (NDGA). An interim analysis was conducted using survival data available on the date at which at least 50 of the male control mice had died at each test site. Survival of control males was significantly higher, at the interim time-point, at UM than at UT or TJL; all three sites had similar survival of control females. Males in the NDGA group had significantly improved survival ( P 0.0004), with significant effects noted at TJL ( P < 0.01) and UT ( P < 0.04). None of the other agents altered survival, although there was a suggestion ( P 0.07) of a beneficial effect of aspirin in males. More data will be needed to determine if any of these compounds can extend maximal lifespan, but the current data show that NDGA reduces early life mortality risks in genetically heterogeneous mice at multiple test sites.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74625/1/j.1474-9726.2007.00311.x.pd

Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice

The National Institute on Aging's Interventions Testing Program was established to evaluate agents that are purported to increase lifespan and delay the appearance of age-related disease in genetically heterogeneous mice. Up to five compounds are added to the study each year and each compound is tested at three test sites (The Jackson Laboratory, University of Michigan, and University of Texas Health Science Center at San Antonio). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen, 4-OH-Α-phenyl-N-tert-butyl nitrone, or nordihydroguaiaretic acid (NDGA). Sample size was sufficient to detect a 10% difference in lifespan in either sex, with 80% power, using data from two of the three sites. Pooling data from all three sites, a log-rank test showed that both NDGA ( p  = 0.0006) and aspirin ( p  = 0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan; neither NDGA ( p  = 0.12) nor aspirin ( p  = 0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on lifespan in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses, might prove to postpone death and various age-related outcomes reproducibly in mice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72117/1/j.1474-9726.2008.00414.x.pd

A non-imaging high throughput approach to chemical library screening at the unmodified adenosine-A3 receptor in living cells

Recent advances in fluorescent ligand technology have enabled the study of G protein-coupled receptors in their native environment without the need for genetic modification such as addition of N-terminal fluorescent or bioluminescent tags. Here, we have used a non-imaging plate reader (PHERAstar FS) to monitor the binding of fluorescent ligands to the human adenosine-A3 receptor (A3AR; CA200645 and AV039), stably expressed in CHO-K1 cells. To verify that this method was suitable for the study of other GPCRs, assays at the human adenosine-A1 receptor, and β1 and β2 adrenoceptors (β1AR and β2AR; BODIPY-TMR-CGP-12177) were also carried out. Affinity values determined for the binding of the fluorescent ligands CA200645 and AV039 to A3AR for a range of classical adenosine receptor antagonists were consistent with A3AR pharmacology and correlated well (R2 = 0.94) with equivalent data obtained using a confocal imaging plate reader (ImageXpress Ultra). The binding of BODIPY-TMR-CGP-12177 to the β1AR was potently inhibited by low concentrations of the β1-selective antagonist CGP 20712A (pKi 9.68) but not by the β2-selective antagonist ICI 118551(pKi 7.40). Furthermore, in experiments conducted in CHO K1 cells expressing the β2AR this affinity order was reversed with ICI 118551 showing the highest affinity (pKi 8.73) and CGP20712A (pKi 5.68) the lowest affinity. To determine whether the faster data acquisition of the non-imaging plate reader (∼3 min per 96-well plate) was suitable for high throughput screening (HTS), we screened the LOPAC library for inhibitors of the binding of CA200645 to the A3AR. From the initial 1,263 compounds evaluated, 67 hits (defined as those that inhibited the total binding of 25 nM CA200645 by ≥40%) were identified. All compounds within the library that had medium to high affinity for the A3AR (pKi ≥6) were successfully identified. We found three novel compounds in the library that displayed unexpected sub-micromolar affinity for the A3AR. These were K114 (pKi 6.43), retinoic acid p-hydroxyanilide (pKi 6.13) and SU 6556 (pKi 6.17). Molecular docking of these latter three LOPAC library members provided a plausible set of binding poses within the vicinity of the established orthosteric A3AR binding pocket. A plate reader based library screening using an untagged receptor is therefore possible using fluorescent ligand opening the possibility of its use in compound screening at natively expressed receptors