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Il contributo presenta uno studio che si propone di analizzare la vasta produzione neologica nell'opera di Jacques Lacan, tanto da un punto di vista teorico (statuto e funzioni del neologismo nella teoria lacaniana), quanto da un punto di vista linguistico (analisi formale dei neologismi lacaniani).

International audience; L'ipotesi ossidativa è in grado di spiegare vari aspetti della sindrome di Rett (RTT), un disturbo pervasivo del neurosviluppo che colpisce quasi esclusivamente il sesso femminile, causato nella maggior parte dei casi da una mutazione del gene X-legato MeCP2 (methyl-CpG binding protein 2). I risultati dei nostri studi indicano che lo sbilanciamento ossidativo è correlato con il tipo di mutazione MeCP2, così come con la storia naturale e l'eterogeneità clinica della malattia. Inoltre l'ipotesi ossidativa è compatibile con la reversibilità potenziale della malattia che è stata dimostrata nei modelli animali sperimentali. Questi risultati indicano anche l'importanza di utilizzare campioni di sangue periferico per monitorare un potenziale danno ossidativo a carico del sistema nervoso centrale e sottolineano il ruolo chiave dell'interazione il chimico organico, l'esperto di stress ossidativo ed il clinico nella ricerca di potenziali nuovi marker nella RTT e l'identificazione di potenziali target terapeutici e strategie di intervento focalizzate al miglioramento della qualità di vita in questi pazienti affetti da una patologia finora incurabile. Ulteriori studi si rendono necessari per comprendere nei dettagli la catena di eventi molecolari che presumibilmente si verificano all'interno della "scatola nera" che lega lo sbilanciamento ossidativo con l'espressione clinica della malattia.

The oxidative stress (OS) hypothesis is able to explain several features of Rett syndrome (RTT), a pervasive development disorder almost exclusively affecting females mainly caused by a mutation in the X-linked methyl-CpG binding protein 2 (MeCP2) gene. In particular, the generation of an OS imbalance is related to MeCP2 gene mutation type, as well as natural history, clinical heterogeneity of the disease, and is compatible with the potential reversibility of the disease observed in the RTT animal models. In addition, our findings indicate the importance of blood as a suitable biological fluid for detecting markers of central nervous system oxidative damage in RTT and underline the key role of interaction between organic chemists, OS biochemists, and clinicians in revealing potential new markers of the disease and identifying potential new targets and interventional strategies aimed at improving the quality of life of these patients, affected by a so far incurable disease. Further efforts in the near future are needed in order to dissect the "black box" of the molecular events likely linking the MeCP2 gene mutation to OS derangement and subsequent disease expression.

Background Rett syndrome (RTT), an X-linked neurodevelopmental rare disease mainly caused by MECP2-gene mutations, is a prototypic intellectual disability disorder. Reversibility of RTT-like phenotypes in an adult mouse model lacking the Mecp2-gene has given hope of treating the disease at any age. However, adult RTT patients still urge for new treatments. Given the relationship between RTT and monoamine deficiency, we investigated mirtazapine (MTZ), a noradrenergic and specific-serotonergic antidepressant, as a potential treatment. Methods Adult heterozygous-Mecp2 (HET) female mice (6-months old) were treated for 30 days with 10 mg/kg MTZ and assessed for general health, motor skills, motor learning, and anxiety. Motor cortex, somatosensory cortex, and amygdala were analyzed for parvalbumin expression. Eighty RTT adult female patients harboring a pathogenic MECP2 mutation were randomly assigned to treatment to MTZ for insomnia and mood disorders (mean age = 23.1 ± 7.5 years, range = 16–47 years; mean MTZ-treatment duration = 1.64 ± 1.0 years, range = 0.08–5.0 years). Rett clinical severity scale (RCSS) and motor behavior assessment scale (MBAS) were retrospectively analyzed. Results In HET mice, MTZ preserved motor learning from deterioration and normalized parvalbumin levels in the primary motor cortex. Moreover, MTZ rescued the aberrant open-arm preference behavior observed in HET mice in the elevated plus-maze (EPM) and normalized parvalbumin expression in the barrel cortex. Since whisker clipping also abolished the EPM-related phenotype, we propose it is due to sensory hypersensitivity. In patients, MTZ slowed disease progression or induced significant improvements for 10/16 MBAS-items of the M1 social behavior area: 4/7 items of the M2 oro-facial/respiratory area and 8/14 items of the M3 motor/physical signs area. Conclusions This study provides the first evidence that long-term treatment of adult female heterozygous Mecp2tm1.1Bird mice and adult Rett patients with the antidepressant mirtazapine is well tolerated and that it protects from disease progression and improves motor, sensory, and behavioral symptoms.

Background Rett syndrome (RTT) is a neurological disorder mainly caused by mutations in MeCP2 gene. It has been shown that MeCP2 impairments can lead to cytokine dysregulation due to MeCP2 regulatory role in T-helper and T-reg mediated responses, thus contributing to the pro-inflammatory status associated with RTT. Furthermore, RTT subjects suffer from an intestinal dysbiosis characterized by an abnormal expansion of the Candida population, a known factor responsible for the hyper-activation of pro-inflammatory immune responses. Therefore, we asked whether the intestinal fungal population of RTT subjects might contribute the sub-inflammatory status triggered by MeCP2 deficiency. Methods We evaluated the cultivable gut mycobiota from a cohort of 50 RTT patients and 29 healthy controls characterizing the faecal fungal isolates for their virulence-related traits, antifungal resistance and immune reactivity in order to elucidate the role of fungi in RTT’s intestinal dysbiosis and gastrointestinal physiology. Results Candida parapsilosis, the most abundant yeast species in RTT subjects, showed distinct genotypic profiles if compared to healthy controls’ isolates as measured by hierarchical clustering analysis from RAPD genotyping. Their phenotypical analysis revealed that RTT’s isolates produced more biofilm and were significantly more resistant to azole antifungals compared to the isolates from the healthy controls. In addition, the high levels of IL-1β and IL-10 produced by peripheral blood mononuclear cells and the mixed Th1/Th17 cells population induced by RTT C. parapsilosis isolates suggest the capacity of these intestinal fungi to persist within the host, being potentially involved in chronic, pro-inflammatory responses. Conclusions Here we demonstrated that intestinal C. parapsilosis isolates from RTT subjects hold phenotypic traits that might favour the previously observed low-grade intestinal inflammatory status associated with RTT. Therefore, the presence of putative virulent, pro-inflammatory C. parapsilosis strains in RTT could represent an additional factor in RTT’s gastrointestinal pathophysiology, whose mechanisms are not yet clearly understood. Electronic supplementary material The online version of this article (10.1186/s12876-018-0785-z) contains supplementary material, which is available to authorized users.

Background Autism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by social and behavioural impairments. In addition to neurological symptoms, ASD subjects frequently suffer from gastrointestinal abnormalities, thus implying a role of the gut microbiota in ASD gastrointestinal pathophysiology. Results Here, we characterized the bacterial and fungal gut microbiota in a cohort of autistic individuals demonstrating the presence of an altered microbial community structure. A fraction of 90% of the autistic subjects were classified as severe ASDs. We found a significant increase in the Firmicutes/Bacteroidetes ratio in autistic subjects due to a reduction of the Bacteroidetes relative abundance. At the genus level, we observed a decrease in the relative abundance of Alistipes, Bilophila, Dialister, Parabacteroides, and Veillonella in the ASD cohort, while Collinsella, Corynebacterium, Dorea, and Lactobacillus were significantly increased. Constipation has been then associated with different bacterial patterns in autistic and neurotypical subjects, with constipated autistic individuals characterized by high levels of bacterial taxa belonging to Escherichia/Shigella and Clostridium cluster XVIII. We also observed that the relative abundance of the fungal genus Candida was more than double in the autistic than neurotypical subjects, yet due to a larger dispersion of values, this difference was only partially significant. Conclusions The finding that, besides the bacterial gut microbiota, also the gut mycobiota contributes to the alteration of the intestinal microbial community structure in ASDs opens the possibility for new potential intervention strategies aimed at the relief of gastrointestinal symptoms in ASDs. Electronic supplementary material The online version of this article (doi:10.1186/s40168-017-0242-1) contains supplementary material, which is available to authorized users.

A strong disatisfaction with the conception and policy prescriptions regarding competitive advantage put forward by the mainstream approach is the general stimulus stirring the present work. Essentially, in this approach, economic policy prescriptions aiming at enhancing the competitive advantage of economic systems are mainly based on two intertwined foundations: equilibrium in a labour market shaped by wage competition and ubiquitous predominance of the comparative advantage principle. In fact, most of the liberalisation and privatisation strategies as well as ‘structural reform’ policies have been conceived and implemented within this analytic scaffold. The principal research question concerns the role of knowledge and competences in structural economic dynamics and business cycle. In particular, we will study the trade-off between the need of change, flexibility and new human resources inputs faced by the firms in the business cycle downswings and the destruction of knowledge and competences taking place in them. The model is based on a very simplified stylisation of the actual working of the economic system. It offers only an aggregate view of the production process. In particular, it concentrates on the impact on firm productivity of some of its key determinants. Since the economic system is typified by a representative firm, the stress is on international competition between different economic systems, rather than on competition between different firms within each system. Given the importance of productivity dynamics, the model shows that even very simple assumptions concerning its determinants can bring about complex paths that soften usual unilateral conjectures about the causal links between productivity and employment. Different configurations of the ‘competence pipeline’ and the related cost functions are explored.

In this essay a model of the learning function is specified and applied to the study of the learning patterns implicit in the job openings by firms, which are converted in demand for skilled labour services. This model makes it possible to focus our attention on some features of the learning processes dynamics whose importance is emphasised in the recent economic literature. The first objective is to understand whether further education and/or training have cumulative effects. The second one is to analyse the modes through which different learning processes can be combined and, in particular, to understand whether complementarity or substitution between them prevails. The third objective is to focus on tenure and on its potential role as a learning device for easing knowledge transfer. Different results are obtained for different sectors and firm dimensions, showing that the institutional and organisational contexts is far from neutral. This suggests that the different components of learning processes should be better selected and combined, primarily through a new approach to the economic organisation of education and training both within and outside the firm.