Nicotinic receptor agonists as neuroprotective/neurotrophic drugs. Progress in molecular mechanisms

In the present work we reviewed recent advances concerning neuroprotective/neurotrophic effects of acute or chronic nicotine exposure, and the signalling pathways mediating these effects, including mechanisms implicated in nicotine addiction and nAChR desensitization. Experimental and clinical data largely indicate long-lasting effects of nicotine and nicotinic agonists that imply a neuroprotective/neurotrophic role of nAChR activation, involving mainly alpha 7 and alpha 4 beta 2 nAChR subtypes, as evidenced using selective nAChR agonists. Compounds interacting with neuronal nAChRs have the potential to be neuroprotective and treatment with nAChR agonists elicits long-lasting neurotrophic effects, e.g. improvement of cognitive performance in a variety of behavioural tests in rats, monkeys and humans. Nicotine addiction, which is mediated by interaction with nACh receptors, is believed to involve the modification of signalling cascades that modulate synaptic plasticity and gene expression. Desensitization, in addition to protecting cells from uncontrolled excitation, is recently considered as a form of signal plasticity. nAChR can generate these longe-lasting effects by elaboration of complex intracellular signals that mediate medium to long-term events crucial for neuronal maintenance, survival and regeneration. Although a comprehensive survey of the gene-based molecular mechanisms that underlie nicotine effects has yet not been performed a growing amount of data is beginning to improve our understanding of signalling mechanisms that lead to neurotrophic/neuroprotective responses. Evidence for an involvement of the fibroblast growth factor-2 gene in nAChR mechanisms mediating neuronal survival, trophism and plasticity has been obtained. However, more work is needed to establish the mechanisms involved in the effects of nicotinic receptor subtype activation from cognition-enhancing and neurotrophic effects to smoking behaviour and to determine more precisely the therapeutic objectives in potential nicotinic drug treatments of neurodegenerative diseases.In the present work we reviewed recent advances concerning neuroprotective/neurotrophic effects of acute or chronic nicotine exposure, and the signalling pathways mediating these effects, including mechanisms implicated in nicotine addiction and nAChR desensitization. Experimental and clinical data largely indicate long-lasting effects of nicotine and nicotinic agonists that imply a neuroprotective/neurotrophic role of nAChR activation, involving mainly alpha 7 and alpha 4 beta 2 nAChR subtypes, as evidenced using selective nAChR agonists. Compounds interacting with neuronal nAChRs have the potential to be neuroprotective and treatment with nAChR agonists elicits long-lasting neurotrophic effects, e.g. improvement of cognitive performance in a variety of behavioural tests in rats, monkeys and humans. Nicotine addiction, which is mediated by interaction with nACh receptors, is believed to involve the modification of signalling cascades that modulate synaptic plasticity and gene expression. Desensitization, in addition to protecting cells from uncontrolled excitation, is recently considered as a form of signal plasticity. nAChR can generate these longe-lasting effects by elaboration of complex intracellular signals that mediate medium to long-term events crucial for neuronal maintenance, survival and regeneration. Although a comprehensive survey of the gene-based molecular mechanisms that underlie nicotine effects has yet not been performed a growing amount of data is beginning to improve our understanding of signalling mechanisms that lead to neurotrophic/neuroprotective responses. Evidence for an involvement of the fibroblast growth factor-2 gene in nAChR mechanisms mediating neuronal survival, trophism and plasticity has been obtained. However, more work is needed to establish the mechanisms involved in the effects of nicotinic receptor subtype activation from cognition-enhancing and neurotrophic effects to smoking behaviour and to determine more precisely the therapeutic objectives in potential nicotinic drug treatments of neurodegenerative diseases

Slow and steady wins the race: Diversification rate is independent from body size and lifestyle in Malagasy skinks (Squamata: Scincidae: Scincinae)

Research data are available on the Mendeley Data platform (https://doi.org/10.17632/xfx2yhw949.2), which include datasets, input files and R scripts of the analyses.Appendix A. Supplementary material Supplementary data to this article can be found online at https://doi. org/10.1016/j.ympev.2022.107635Most of the unique and diverse vertebrate fauna that inhabits Madagascar derives from in situ diversification from colonisers that reached this continental island through overseas dispersal. The endemic Malagasy Scincinae lizards are amongst the most species-rich squamate groups on the island. They colonised all bioclimatic zones and display many ecomorphological adaptations to a fossorial (burrowing) lifestyle. Here we propose a new phylogenetic hypothesis for their diversification based on the largest taxon sampling so far compiled for this group. We estimated divergence times and investigated several aspects of their diversification (diversification rate, body size and fossorial lifestyle evolution, and biogeography). We found that diversification rate was constant throughout most of the evolutionary history of the group, but decreased over the last 6–4 million years and independently from body size and fossorial lifestyle evolution. Fossoriality has evolved from fully quadrupedal ancestors at least five times independently, which demonstrates that even complex morphological syndromes – in this case involving traits such as limb regression, body elongation, modification of cephalic scalation, depigmentation, and eyes and ear-opening regression – can evolve repeatedly and independently given enough time and eco-evolutionary advantages. Initial diversification of the group likely occurred in forests, and the divergence of sand-swimmer genera around 20 Ma appears linked to a period of aridification. Our results show that the large phenotypic variability of Malagasy Scincinae has not influenced diversification rate and that their rich species diversity results from a constant accumulation of lineages through time. By compiling large geographic and trait-related datasets together with the computation of a new time tree for the group, our study contributes important insights on the diversification of Malagasy vertebrates.Portuguese National Funds through FCT (Fundação para a Ciência e a Tecnologia) supported this work with the projects UIDP/50027/2020 and PTDC/BIA-EVL/31254/2017Contract grant to AC [2020.00823.CEECIND/CP1601/CT0003PD/BD/128493/2017SFRH/BD/102495/2014SFRH/BPD/111015/2015Agencia Española de Investigación, with a Juan de la Cierva-Formación grant [FCI2019-039443-I/AEI/10.13039/501100011033]Swedish Research Council [2019-05191]Swiss National Science Foundation [PCEFP3_187012]Swedish Research Council [VR: 2019-04739

mGluR2/3 agonist LY379268, by enhancing the production of GDNF, induces a time-related phosphorylation of RET receptor and intracellular signaling Erk1/2 in mouse striatum.

In the present study we aimed to verify if the enhancement of glial cell line-derived neurotrophic factor (GDNF) production in mouse striatum following treatment with LY379268 may also induce in the nigrostriatal system a time-related activation of RET receptor and its specific intracellular signaling. For this purpose, we have investigated the effects of LY379268 treatment on RET phosphorylation at the Tyr1062 and on downstream signaling Erk1/2, Akt and PLCγ1 pathway activation. The results showed that treatment with LY379268 (3 mg/kg) induces a significant increase of GDNF levels and time-related RET and Erk1/2 phosphorylation in the striatum. These increases were detected at 24 h and 48 h following LY379268 treatment. No changes were observed in the Akt and PLCγ1 phosphorylation levels. Similar results for p-Erk1/2 were observed in the substantia nigra. A complete block of LY379268 effect on striatal RET and p-Erk1/2 phosphorylation was observed in mice intrastriatal injected with anti-GDNF antibodies, suggesting a correlation between GDNF upregulation and RET activation. Overall, with present data we have shown that activation of mGluR2/3 receptors by LY379268 may be particularly promising for nigrostriatal dopaminergic system protection by enhancing striatal levels of GDNF/RET trophic system activity

I business model bancari tra vigilanza, riforme strutturali e crisi.

L’impatto della recente crisi finanziaria sull’economia mondiale è stato talmente grave da indurre policy makers, autorità di vigilanza e intermediari ad un ripensamento circa la regolamentazione finanziaria. Tra i diversi aspetti che hanno catturato l’attenzione dei regulators in questi anni vi è sicuramente l’importanza assunta dai modelli di business bancari. A partire dagli anni ’70 con la deregolamentazione dei mercati finanziari e con l’avvento dell’innovazione finanziaria si è affermato progressivamente il modello della banca universale in grado di offrire un ampia gamma di servizi, da quelli core destinati alla clientela retail a quelli a più alto valore aggiunto tipici dell’investment banking. La maggiore complessità di questo modello si è spesso accompagnata a dimensioni sempre maggiori, dando vita in casi estremi al cosiddetto fenomeno degli intermediari TBTF (Too big to fail). Una conseguenza diretta dell’evoluzione dei modelli di business è stato un cambiamento significativo del settore bancario nel complesso, infatti sul sistema hanno gravato rischi sempre maggiori tra i quali quelli di mercato e di liquidità. A seguito delle tristi vicende che hanno coinvolto importanti istituti di credito attivi a livello internazionale e che hanno comportato operazioni di salvataggio da parte dei governi nazionali, sono sorti dei dubbi circa la sostenibilità nel lungo periodo di determinati modelli di business. Tale consapevolezza ha spinto molti Paesi, tra i quali Stati Uniti, Regno Unito, Francia, Germania e Belgio a prendere in considerazione delle riforme strutturali in grado di rendere il settore bancario più stabile e trasparente. Elemento comune di tali iniziative è la previsione di una separazione tra le attività dell’intermediario; l’intento è quello di creare una separazione tra l’anima commerciale e quella altamente speculativa dello stesso, in modo da garantire l’operatività di base della banca anche in caso di crisi dell’entità dedita alla negoziazione di titoli sui mercati. Nel corso del primo capitolo della presente trattazione sarà dedicato un ampio spazio alla tematica dei modelli di business bancari, in particolare, una volta definito il concetto di modello di business sarà analizzata la relazione tra questo e le performance dell’intermediario, tenendo conto anche del profilo di rischio dello stesso. Nel corso del secondo capitolo, invece, sarà condotta un’analisi empirica sui modelli di business degli intermediari europei rilevanti a livello sistemico (G-SIBs). Segnatamente, sulla base di informazioni pubblicamente disponibili, si farà un confronto tra le performance e i profili di rischio dei due possibili modelli di business adottati da tali intermediari (retail oriented e investment oriented). Contestualmente sarà riportato il cambiamento di BNP Paribas relativamente alla composizione di alcune voci di bilancio che fa presumere un’evoluzione del modello di business. Nel terzo capitolo infine, si passeranno in rassegna le iniziative di riforma strutturale del sistema intraprese sia a livello comunitario che dai singoli Paesi. Nel corso dello stesso capitolo si avanzeranno delle considerazioni circa il possibile impatto di tali iniziative sul sistema e sui modelli di business in generale

L'INFORMATIVA DI SEGMENTO NEI BILANCI DELLE SOCIETA' QUOTATE: UN'INDAGINE EMPIRICA

Nel lavoro svolto, dopo aver argomentato lo IAS 14, verranno presentati i risultati di un'indagine empirica condotta su un campione di societa' quotate

Uncertainty in calibration and characterisation of pyranometers

This work quantifies the uncertainties of thermoelectric pyranometer measurements made with different calibration methods. Measurement campaigns supported both the evaluation of pyranometer calibrations and newly proposed approaches to characterise the pyranometers in indoor and outdoor conditions. Estimated uncertainties were then applied to a year-long irradiance dataset to evaluate the impact on the assessment of the annual solar irradiation. This study highlights the differences seen when calibrating pyranometers under different conditions and procedures. Such deeper insight of pyranometers response aims ultimately to assist the integration of short-term (pyranometers) and long-term (satellite-based) data to a more accurate evaluation of PV energy yield

Problemi metodologici nello studio del processo psicoterapico e nella valutazione dell’attaccamento e del rischio psicopatologico in adolescenza

Il gruppo di ricerca che attualmente opera presso il Dipartimento di Psicologia Dinamica e Clinica, ha orientato il proprio lavoro fondamentalmente attorno a due tematiche: lo studio multidimensionale del processo terapeutico (in una prospettiva tanto empirica quanto di ricerca concettuale); la rilevanza della teoria dell’attaccamento e dei sistemi motivazionali per la comprensione dello sviluppo della patologia di personalità e delle sue manifestazioni nel contesto clinico, con particolare riferimento all'adolescenza.Our research group, currently operating at the Department of Dynamic and Clinic Psychology, have mainly focused on two topics: the study on therapeutic process (in the perspectives of both empirical and conceptual research); the relevance of attachment theory for the understanding of abnormal personality development and its manifestations within the clinical context, with specific reference to adolescence

Identification of calcium sensing receptor (CaSR) mRNA-expressing cells in normal and injured rat brain

Calcium sensing receptor (CaSR), isolated for the first time from bovine and human parathyroid, is a G-protein-coupled receptors that has been involved in diverse physiological functions. At present a complete in vivo work on the identification of CaSR mRNA-expressing cells in the adult brain lacks and this investigation was undertaken in order to acquire more information on cell type expressing CaSR mRNA in the rat brain and to analyse for the first time its expression in different experimental models of brain injury. The expression of CaSR mRNAs was found mainly in scattered cells throughout almost all the brain regions. A double labeling analysis showed a colocalization of CaSR mRNA expression in neurons and oligodendrocytes, whereas it was not found expressed both in the microglia and in astrocytes. One week after kainate-induced seizure CaSR was found in the injured CA3 region of the hippocampus and very interestingly it was found up-regulated in the neurons of CA1-CA2 and dentate gyrus. Similarly, 1 week following ibotenic acid injection in the hippocampus, CaSR mRNA expression was increased in oligodendrocytes both in the lesioned area and in the contralateral CA1-CA3 pyramidal cell layers and dentate gyrus. One week after needle-induced mechanical lesion an increase of labeled cells expressing CaSR mRNA was observed along the needle track. In conclusion, the present results contribute to extend available data on cell type-expressing CaSR in normal and injured brain and could spur to understand the role of CaSR in repairing processes of brain injury

Early social adversity modulates the relation between attention biases and socioemotional behaviour in juvenile macaques

Affect-biased attention may play a fundamental role in early socioemotional development, but factors influencing its emergence and associations with typical versus pathological outcomes remain unclear. Here, we adopted a nonhuman primate model of early social adversity (ESA) to: (1) establish whether juvenile, pre-adolescent macaques demonstrate attention biases to both threatening and reward-related dynamic facial gestures; (2) examine the effects of early social experience on such biases; and (3) investigate how this relation may be linked to socioemotional behaviour. Two groups of juvenile macaques (ESA exposed and non-ESA exposed) were presented with pairs of dynamic facial gestures comprising two conditions: neutral-threat and neutral-lipsmacking. Attention biases to threat and lipsmacking were calculated as the proportion of gaze to the affective versus neutral gesture. Measures of anxiety and social engagement were also acquired from videos of the subjects in their everyday social environment. Results revealed that while both groups demonstrated an attention bias towards threatening facial gestures, a greater bias linked to anxiety was demonstrated by the ESA group only. Only the non-ESA group demonstrated a significant attention bias towards lipsmacking, and the degree of this positive bias was related to duration and frequency of social engagement in this group. These findings offer important insights into the effects of early social experience on affect-biased attention and related socioemotional behaviour in nonhuman primates, and demonstrate the utility of this model for future investigations into the neural and learning mechanisms underlying this relationship across development