MicroRNAs and cancer metabolism reprogramming : the paradigm of metformin

Increasing evidence witnesses that cancer metabolism alterations represent a critical hallmark for many types of human tumors. There is a strong need to understand and dissect the molecular mechanisms underlying cancer metabolism to envisage specific biomarkers and underpin critical molecular components that might represent novel therapeutic targets. One challenge, that is the focus of this review, is the reprogramming of the altered metabolism of a cancer cell toward that of un-transformed cell. The anti-hyperglicemic agent, metformin has proven to be effective in reprogramming the metabolism of cancer cells even from those subpopulations endowed with cancer stem like features and very high chemoresistenace to conventional anticancer treatments. A functional interplay involving selective modulation of microRNAs (miRNAs) takes place along the anticancer metabolic effects exerted by metformin. The implications of this interplay will be also discussed in this review

The Impact of Work-Related Barriers on Job Satisfaction of Practitioners Working with Migrants

Abstract The work environment of practitioners working with migrants may be very demanding as they are frequently exposed to the sad narratives of such a vulnerable population, the lack of professional support, or the frequent change of policies towards refugees and asylum seekers. Little research has been conducted to explore the job satisfaction of practitioners working with migrants and the organizational characteristics that can hinder or promote such satisfaction. The present study investigated the relationship between work-related barriers (i.e., intra-organizational, legal, and interaction-related barriers) and job satisfaction of practitioners working with migrants, also testing if perceived organizational efficacy is mediating this relation. This study was part of a larger European funded project, and participants were 428 First-Line Practitioners working with migrants in various sectors (e.g., social and health services, immigration and asylum services, or border guards) and working in several European countries. Data were collected through an online survey in the period between October and December 2020. Results showed that intra-organizational and legal barriers had a negative impact on job satisfaction, while interaction-related barriers did not have any. Perceived organizational efficacy mediated the relationship between two work-related barriers (intra-organizational and interaction-related barriers) and job satisfaction. These findings suggest that organizations working with migrants should focus on addressing intra-organizational and legal barriers, and on implementing actions aimed at building employees’ collective efficacy beliefs to improve their job satisfaction

The role of Gpi-anchored axonal glycoproteins in neural development and neurological disorders.

This review article focuses on the Contactin (CNTN) subset of the Immunoglobulin supergene family (IgC2/FNIII molecules), whose components share structural properties (the association of Immunoglobulin type C2 with Fibronectin type III domains), as well as a general role in cell contact formation and axonal growth control. IgC2/FNIII molecules include 6 highly related components (CNTN 1-6), associated with the cell membrane via a Glycosyl Phosphatidyl Inositol (GPI)-containing lipid tail. Contactin 1 and Contactin 2 share ~50 (49.38)% identity at the aminoacid level. They are components of the cell surface, from which they may be released in soluble forms. They bind heterophilically to multiple partners in cis and in trans, including members of the related L1CAM family and of the Neurexin family Contactin-associated proteins (CNTNAPs or Casprs). Such interactions are important for organising the neuronal membrane, as well as for modulating the growth and pathfinding of axon tracts. In addition, they also mediate the functional maturation of axons by promoting their interactions with myelinating cells at the nodal, paranodal and juxtaparanodal regions. Such interactions also mediate differential ionic channels (both Na(+) and K(+)) distribution, which is of critical relevance in the generation of the peak-shaped action potential. Indeed, thanks to their interactions with Ankyrin G, Na(+) channels map within the nodal regions, where they drive axonal depolarization. However, no ionic channels are found in the flanking Contactin1-containing paranodal regions, where CNTN1 interactions with Caspr1 and with the Ig superfamily component Neurofascin 155 in cis and in trans, respectively, build a molecular barrier between the node and the juxtaparanode. In this region K(+) channels are clustered, depending upon molecular interactions with Contactin 2 and with Caspr2. In addition to these functions, the Contactins appear to have also a role in degenerative and inflammatory disorders: indeed Contactin 2 is involved in neurodegenerative disorders with a special reference to the Alzheimer disease, given its ability to work as a ligand of the Alzheimer Precursor Protein (APP), which results in increased Alzheimer Intracellular Domain (AICD) release in a γ-secretase-dependent manner. On the other hand Contactin-1 drives Notch signalling activation via the Hes pathway, which could be consistent with its ability to modulate neuroinflammation events, and with the possibility that Contactin 1-dependent interactions may participate to the pathogenesis of the Multiple Sclerosis and of other inflammatory disorders

On the role of the cellular prion protein in the uptake and signaling of pathological aggregates in neurodegenerative diseases

Neurodegenerative disorders are associated with intra- or extra-cellular deposition of aggregates of misfolded insoluble proteins. These deposits composed of tau, amyloid-\u3b2 or \u3b1-synuclein spread from cell to cell, in a prion-like manner. Novel evidence suggests that the circulating soluble oligomeric species of these misfolded proteins could play a major role in pathology, while insoluble aggregates would represent their protective less toxic counterparts. Recent convincing data support the proposition that the cellular prion protein, PrPC, act as a toxicity-inducing receptor for amyloid-\u3b2 oligomers. As a consequence, several studies focused their investigations to the role played by PrPC in binding other protein aggregates, such as tau and \u3b1-synuclein, for its possible common role in mediating toxic signalling. The biological relevance of PrPC as key ligand and potential mediator of toxicity for multiple proteinaceous aggregated species, prions or PrPSc included, could lead to relevant therapeutic implications. Here we describe the structure of PrPC and the proposed interplay with its pathological counterpart PrPSc and then we recapitulate the most recent findings regarding the role of PrPC in the interaction with aggregated forms of other neurodegeneration-associated proteins

Altered White-Matter Microstructure in Conduct Disorder Is Specifically Associated with Elevated Callous-Unemotional Traits

Adolescents with conduct disorder (CD) and elevated callous-unemotional (CU) traits have been reported to present with a more severe and persistent pattern of antisocial behaviour than those with low levels of CU traits. However, relatively few studies have investigated whether there are differences in brain structure between these subgroups.We acquired diffusion tensor imaging data and used tract-based spatial statistics (TBSS) to compare adolescents with CD and high levels of CU traits (CD/CU+; n = 18, CD and low levels of CU traits (CD/CU-; n = 17) and healthy controls (HC; n = 32) on measures of fractional anisotropy (FA), axial (AD), radial (RD) and mean (MD) diffusivity. Compared to CD/CU- adolescents, those with CD/CU+ presented increased FA and reduced RD and MD (lower diffusivity) in several tracts including: body and splenium of the corpus callosum, right inferior longitudinal fasciculus, ILF; right inferior fronto-occipital fasciculus, IFOF; left superior longitudinal fasciculus, SLF; left cerebral peduncle, bilateral internal capsule, left superior and posterior corona radiata, bilateral thalamic radiation and left external capsule. In addition, relative to CD/CU- individuals, adolescents with CD/CU+ showed lower diffusivity (indexed by reduced RD and MD) in left uncinate fasciculus and bilateral fornix. Finally, relative to healthy controls, CD/CU+ individuals showed lower diffusivity (reduced RD) in the genu and body of the corpus callosum and left anterior corona radiata. These results suggest that CD/CU+ individuals present with white-matter microstructural abnormalities compared to both CD/CU- individuals and age-matched healthy controls. This finding is consistent with emerging evidence suggesting that CD/CU+ represents a distinct subtype of CD, and illustrates the importance of accounting for heterogeneity within CD populations

Exact relations between damage spreading and thermodynamic functions for the N-color Ashkin-Teller model

Exact results are derived relating quantities computable by the so-called damage spreading method and thermodynamic functions for the N-color Ashkin-Teller model. The results are valid for any ergodic dynamics. Since we restrict our analysis to the ferromagnetic case the results are also valid for any translational invariant lattice. The derived relations should be used in order to determine numerically the N-color Ashkin-Teller critical exponents with better accuracy and less computational efforts than standard Monte Carlo simulations.Comment: 6 pages, to be published in JSTAT (Journal of Statistical Mechanics: Theory and Experiment). The results of a computer simulation were included for N=3 as an example on how to use the analytical relations derived in the paper as a guide to obtain the critical temperature and critical exponent

Scaling of spin avalanches in growing networks

Growing networks decorated with antiferromagnetically coupled spins are archetypal examples of complex systems due to the frustration and the multivalley character of their energy landscapes. Here we use the damage spreading method (DS) to investigate the cohesion of spin avalanches in the exponential networks and the scale-free networks. On the contrary to the conventional methods, the results obtained from DS suggest that the avalanche spectra are characterized by the same statistics as the degree distribution in their home networks. Further, the obtained mean range $Z$ of an avalanche, i.e. the maximal distance reached by an avalanche from the damaged site, scales with the avalanche size $s$ as $Z/N^\beta =f(s/N^{\alpha})$, where $\alpha=0.5$ and $\beta=0.33$. These values are true for both kinds of networks for the number $M$ of nodes to which new nodes are attached between 4 and 10; a check for M=25 confirms these values as well.Comment: 10 pages, 9 figures. More data in Fig.

Fluoxetine and vortioxetine reverse depressive-like phenotype and memory deficits induced by Aβ1-42 oligomers in mice: A key role of transforming growth factor-β1

Depression is a risk factor for the development of Alzheimer's disease (AD), and the presence of depressive symptoms significantly increases the conversion of mild cognitive impairment (MCI) into AD. A long-term treatment with antidepressants reduces the risk to develop AD, and different second-generation antidepressants such as selective serotonin reuptake inhibitors (SSRIs) are currently being studied for their neuroprotective properties in AD. In the present work, the SSRI fluoxetine and the new multimodal antidepressant vortioxetine were tested for their ability to prevent memory deficits and depressive-like phenotype induced by intracerebroventricular injection of amyloid-beta (1-42) (A beta(1-42)) oligomers in 2-month-old C57BL/6 mice. Starting from 7 days before A beta injection, fluoxetine (10 mg/kg) and vortioxetine (5 and 10 mg/kg) were intraperitoneally injected daily for 24 days. Chronic treatment with fluoxetine and vortioxetine (both at the dose of 10 mg/kg) was able to rescue the loss of memory assessed 14 days after A beta injection by the passive avoidance task and the object recognition test. Both antidepressants reversed the increase in immobility time detected 19 days after A beta injection by forced swim test. Vortioxetine exerted significant antidepressant effects also at the dose of 5 mg/kg. A significant deficit of transforming growth factor-beta 1 (TGF-beta 1), paralleling memory deficits and depressive-like phenotype, was found in the hippocampus of A beta -injected mice in combination with a significant reduction of the synaptic proteins synaptophysin and PSD-95. Fluoxetine and vortioxetine completely rescued hippocampal TGF-beta 1 levels in A beta -injected mice as well as synaptophysin and PSD-95 levels. This is the first evidence that a chronic treatment with fluoxetine or vortioxetine can prevent both cognitive deficits and depressive-like phenotype in a non-transgenic animal model of AD with a key contribution of TGF-beta 1