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The objective of the present article, without pretending make an exhaustive analysis about the cultural tourism, is to introduce some reflections about this way of tourism from different points of view. Firstly, it will broach the relationship between cultural tourism and globalisation, and then it will be centered in the incidence of this activity as factor of local and regional development, specially considering some examples in Argentina.It will also try to introduce the discussion about their the positive and negative aspects, or strengths and weaknesses of cultural tourism. Finally, it will comment some considerations about the role of the international bodies and the agencies of cooperation, including the most significant declarations, resolutions and recomendations in this field

Nervous system development involves proliferation and cell specification of progenitor cells into neurons and glial cells. Unveiling how this complex process is orchestrated under physiological conditions and deciphering the molecular and cellular changes leading to neurological diseases is mandatory. To date, great efforts have been aimed at identifying gene mutations associated with many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Mutations in the RNA/DNA binding protein Fused in Sarcoma/Translocated in Liposarcoma (FUS/TLS) have been associated with motor neuron degeneration in rodents and humans. Furthermore, increased levels of the wild-type protein can promote neuronal cell death. Despite the well-established causal link between FUS mutations and ALS, its role in neural cells remains elusive. In order to shed new light on FUS functions we studied its role in the control of neural stem progenitor cell (NSPC) properties. Here, we report that human wild-type Fused in Sarcoma (WT FUS), exogenously expressed in mouse embryonic spinal cord-derived NSPCs, was localized in the nucleus, caused cell cycle arrest in G1 phase by affecting cell cycle regulator expression, and strongly reduced neuronal differentiation. Furthermore, the expression of the human mutant form of FUS (P525L-FUS), associated with early-onset ALS, drives the cells preferentially towards a glial lineage, strongly reducing the number of developing neurons. These results provide insight into the involvement of FUS in NSPC proliferation and differentiation into neurons and glia.

Young adults with personality disorders (PD) other than borderline are in urgent need of validated treatments to help them in managing important life transitions. Therapeutic interventions focused upon social and interpersonal difficulties may facilitate these individuals in maximizing opportunities for employment, forming stable romantic relationships, and belong to social groups. It is also important that they are offered evidence-based, first-line time-limited treatments in order to maximize effectiveness and reduce costs. We developed a 16-session programme of group-based Metacognitive Interpersonal Therapy (MIT-G) including psychoeducation on the main interpersonal motives, an experiential component enabling practice of awareness of mental states; and use of mentalistic knowledge for purposeful problem-solving. We report a feasibility, acceptability, and clinical significance randomized clinical trial. Participants meeting inclusion criteria were randomized to receive MIT-G (n = 10) or waiting list+TAU (n = 10). Dropout rate was low and session attendance high (92.19%). Participants in the MIT-G arm had symptomatic and functional improvements consistent with large effect sizes. In the MIT-G arm similarly large effects were noted for increased capacity to understand mental states and regulate social interactions using mentalistic knowledge. Results were sustained at follow-up. Our findings suggest potential for applying MIT-G in larger samples to further test its effectiveness in reducing PD-related symptoms and problematic social functioning., (© 2018 The British Psychological Society.)

Mutations of Fused in sarcoma (FUS), a ribonucleoprotein involved in RNA metabolism, have been found associated with both familial and sporadic cases of amyotrophic lateral sclerosis (ALS). Notably, besides mutations in the coding sequence, also mutations into the 3' untranslated region, leading to increased levels of the wild-type protein, have been associated with neuronal death and ALS pathology, in ALS models and patients. The mechanistic link between altered FUS levels and ALS-related neurodegeneration is far to be elucidated, as well as the consequences of elevated FUS levels in the modulation of the inflammatory response sustained by glial cells, a well-recognized player in ALS progression. Here, we studied the effect of wild-type FUS overexpression on the responsiveness of mouse and human neural progenitor-derived astrocytes to a pro-inflammatory stimulus (IL1β) used to mimic an inflammatory environment. We found that astrocytes with increased FUS levels were more sensitive to IL1β, as shown by their enhanced expression of inflammatory genes, compared with control astrocytes. Moreover, astrocytes overexpressing FUS promoted neuronal cell death and pro-inflammatory microglia activation. We conclude that overexpression of wild-type FUS intrinsically affects astrocyte reactivity and drives their properties toward pro-inflammatory and neurotoxic functions, suggesting that a non-cell autonomous mechanism can support neurodegeneration in FUS-mutated animals and patients.

Patients with personality disorders (PDs) other than borderline, with prominent features of social inhibition and over-regulation of emotions, are in need of specialized treatments. Individuals present with poor metacognition, that is the capacity to understand mental states and use psychological knowledge for the sake of purposeful problem solving; and are guided by maladaptive interpersonal schemas. We developed a short-term group intervention, Metacognitive Interpersonal Therapy in Groups (MIT-G), incorporating psychoeducational and experiential elements, to help these individuals become more aware of their drives when interacting with others; and to help them adopt more flexible behaviors via improvements in metacognition. We present results of an effectiveness study, evaluating whether we could replicate the initial positive results of our first pilot randomized controlled trial. Seventeen young adults outpatients with personality disorders were included in the 16 session program. Effect sizes were calculated for change from baseline to treatment end for the primary outcome, symptoms and functioning (Clinical Outcomes in Routine Evaluation Outcome Measure) and then for one putative mechanism of change - metacognition. Emotional dysregulation and alexithymia were also assessed. Qualitative evaluations of the acceptability and subjective impact of the treatment were also performed. MIT-G was acceptable to participants. There were medium to large magnitude changes from pre- to post- treatment on wellbeing, emotion dysregulation, alexithymia and metacognition. These gains were maintained at follow-up. There was evidence of clinically significant change on key variables. MITG appears acceptable to patients, as evidenced by the absence of drop-out from treatment. In light of the positive outcomes of this study and the expanding evidence base, MIT-G is a candidate for dissemination and investigations in larger trials as a possible effective intervention for PDs characterized by tendencies to overcontrol., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest., (©Copyright R. Popolo et al., 2018.)

In adult mammals, neural stem cells (NSCs) reside in specialized niches at the level of selected CNS regions, such as the subventricular zone (SVZ). The signaling pathways that reg-ulate NSC proliferation and differentiation remain poorly understood. Early growth response protein 1 (Egr-1) is an important transcription factor, widely studied in the adult mammalian brain, mediating the activation of target genes by a variety of extracellular stimuli. In our study, we aimed at testing how Egr-1 regulates adult NSCs derived from mouse SVZ and, in particular, the interplay between Egr-1 and the proliferative factor EGF. We demonstrate that Egr-1 expression in NSCs is induced by growth factor stimulation, and its level decreases after EGF deprivation or by using AG1478, an inhibitor of the EGF/EGFR signaling pathway. We also show that Egr-1 overexpression rescues the cell proliferation decrease observed either after EGF removal or upon treatment with AG1478, suggesting that Egr-1 works downstream of the EGF pathway. To better understand this mechanism, we investigated targets downstream of both the EGF pathway and Egr-1, and found that they regulate genes involved in NSC proliferation, such as cell cycle regulators, cyclins, and cyclin-dependent kinase inhibitors., (© 2018 S. Karger AG, Basel.)

Adult neural stem cell (aNSC) activity is tuned by external stimuli through the recruitment of transcription factors. This study examines the RE1 silencing transcription factor (REST) in neural stem/progenitor cells isolated from the subventricular zone of adult mouse brain and provides the first extensive characterization of REST-mediated control of the cellular and molecular properties. This study shows that REST knockdown affects the capacity of progenitor cells to generate neurospheres, reduces cell proliferation, and triggers cell differentiation despite the presence of growth factors. Genome- and transcriptome-wide analyses show that REST binding sites are significantly enriched in genes associated with synaptic transmission and nervous system development and function. Seeking candidate regulators of aNSC function, this study identifies a member of the bone morphogenetic protein (BMP) family, BMP6, the mRNA and protein of which increased after REST knockdown. The results of this study extend previous findings, demonstrating a reciprocal control of REST expression by BMPs. Administration of exogenous BMP6 inhibits aNSC proliferation and induces the expression of the astrocytic marker glial fibrillary acidic protein, highlighting its antimitogenic and prodifferentiative effects. This study suggests that BMP6 produced in a REST-regulated manner together with other signals can contribute to regulation of NSC maintenance and fate., (© 2015 Wiley Periodicals, Inc.)

β-cell mass in the pancreas increases significantly during pregnancy as an adaptation to maternal insulin resistance. Lineage tracing studies in rodents have presented conflicting evidence on the role of cell duplication in the formation of new β-cells during gestation, while recent human data suggest that new islets are a major contributor to increased β-cell mass in pregnancy. Here, we aim to: 1) determine whether a non-β-cell source contributes to the appearance of new β-cells during pregnancy and 2) investigate whether recapitulation of the embryonic developmental pathway involving high expression of neurogenin 3 (Ngn3) plays a role in the up-regulation of β-cell mass during pregnancy. Using a mouse β-cell lineage-tracing model, which labels insulin-producing β-cells with red fluorescent protein (RFP), we found that the percentage of labeled β-cells dropped from 97% prior to pregnancy to 87% at mid-pregnancy. This suggests contribution of a non-β-cell source to the increase in total β-cell numbers during pregnancy. In addition, we observed a population of hormone-negative, Ngn3-positive cells in islets of both non-pregnant and pregnant mice, and this population dropped from 12% of all islets cells in the non-pregnant mice to 5% by day 8 of pregnancy. Concomitantly, a decrease in expression of Ngn3 and changes in its upstream regulatory network (Sox9 and Hes-1) as well as downstream targets (NeuroD, Nkx2.2, Rfx6 and IA1) were also observed during pregnancy. Our results show that duplication of pre-existing β-cells is not the sole source of new β-cells during pregnancy and that Ngn3 may be involved in this process.

Musashi1 is an RNA binding protein that controls the neural cell fate, being involved in maintaining neural progenitors in their proliferative state. In particular, its downregulation is needed for triggering early neural differentiation programs. In this study, we profiled microRNA expression during the transition from neural progenitors to differentiated astrocytes and underscored 2 upregulated microRNAs, miR-23a and miR-125b, that sinergically act to restrain Musashi1 expression, thus creating a regulatory module controlling neural progenitor proliferation.