Opinion dynamics and synchronization in a network of scientific collaborations

In this paper we discuss opinion dynamics in the Opinion Changing Rate (OCR) model, recently proposed (A.Pluchino, V.Latora and A.Rapisarda Int. J. Mod. Phys. C, 16, No.4, 515-531 (2005)). The OCR model allows to study whether and how a group of social agents, with a different intrinsic tendency rate to change opinion, finds agreement. In particular, we implement the OCR model on a small graph describing the topology of a real social system. The nodes of the graph are scientists partecipating to the Tepoztlan conference, celebrating Alberto Robledo's 60th birthday, and the links are based on coauthorship in scientific papers. We study how opinions evolve in time according to the frequency rates of the nodes, to the coupling term, and also to the presence of group structures.Comment: 15 pages, 4 figures, Physica A (2006) in pres

Inside-out: unpredicted Annexin A2 localisation on the surface of extracellular vesicles

This is the author accepted manuscript. The final version is available from Science Matters via https://www.sciencematters.io/articles/201602000015Inside-out: unpredicted Annexin A2 localisation on the surface of extracellular vesicles Extracellular vesicles (EVs) contain many proteins, both cytosolic and surface bound. The current model for EV biogenesis dictates that cytosolic proteins remain in the lumen and cell surface proteins reside on the outside of vesicles. This is consistent with the traditional protein trafficking pathway, where proteins destined for the plasma membrane contain a signal sequence targeting them to the secretory pathway. According to this ‘classical’ pathway for membrane and secretory protein trafficking, proteins lacking a signal sequence should not reside at the cell surface. It has been shown that transmembrane proteins are retained in the membrane of EVs and RNAs reside in the lumen of EVs. However, there is little known about the packaging and location of other proteins enriched in EVs. Annexin A2 is a cytosolic protein abundant in EVs. We show for the first time that Annexin A2 is expressed not only in the lumen of EVs as predicted but also on the surface of EVs. This raises fundamental questions regarding Annexin A2 transport to the outer leaflet of the EV membrane as it lacks a signal peptide for secretion.This work was supported by Wellcome Trust Strategic Award [100574/Z/12/Z] and MRC Metabolic Diseases Unit [MRC_MC_UU_12012/5], from the Italian Multiple Sclerosis Association (AISM, grant 2010/R/31), the Italian Ministry of Health (GR08-7), the European Research Council (ERC) under the ERC-2010-StG Grant agreement n° 260511-SEM_SEM, the UK Regenerative Medicine Platform Acellular hub (Partnership award RG69889), and core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute. FG is supported by a scholarship of the Gates Cambridge Trust

The role of immune cells, glia and neurons in white and gray matter pathology in multiple sclerosis.

Multiple sclerosis is one of the most common causes of chronic neurological disability beginning in early to middle adult life. Multiple sclerosis is idiopathic in nature, yet increasing correlative evidence supports a strong association between one's genetic predisposition, the environment and the immune system. Symptoms of multiple sclerosis have primarily been shown to result from a disruption in the integrity of myelinated tracts within the white matter of the central nervous system. However, recent research has also highlighted the hitherto underappreciated involvement of gray matter in multiple sclerosis disease pathophysiology, which may be especially relevant when considering the accumulation of irreversible damage and progressive disability. This review aims at providing a comprehensive overview of the interplay between inflammation, glial/neuronal damage and regeneration throughout the course of multiple sclerosis via the analysis of both white and gray matter lesional pathology. Further, we describe the common pathological mechanisms underlying both relapsing and progressive forms of multiple sclerosis, and analyze how current (as well as future) treatments may interact and/or interfere with its pathology. Understanding the putative mechanisms that drive disease pathogenesis will be key in helping to develop effective therapeutic strategies to prevent, mitigate, and treat the diverse morbidities associated with multiple sclerosis.The authors thank Dr. Gillian Tannahill and Prof. Alasdair Coles for critically reviewing the article, and Prof. Kenneth J Smith for the illuminating discussions on MS pathophysiology. We acknowledge the contribution of past and present members of Pluchino laboratory, who have contributed to (or inspired) this manuscript. Research in the author’s laboratory is supported by the National Multiple Sclerosis Society (NMSS; RG-4001-A1), the Italian Multiple Sclerosis Foundation (FISM; RG 2010/R/31), the Italian Ministry of Health (GR08/7) the European Research Council (ERC) 2010-StG (RG 260511-SEM_SEM), the European Community (EC) 7th Framework Program (FP7/2007–2013; RG 280772-iONE), The Evelyn Trust (RG 69865), The Bascule Charitable Trust (RG 75149), The Great Britain Sakakawa Foundation and a core support grant from the Wellcome Trust and MRC to the Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute. GM was supported by an European Neurological Society (ENS) Training fellowship. LPJ was supported by the Wellcome Trust [RRZA/057 RG79423]. JDB was supported by a NIH-OxCam fellowship.This is the final version of the article. It was first available from Elsevier via http://dx.doi.org/10.1016/j.pneurobio.2015.02.00

Mesenchymal Stem Cells as Promoters, Enhancers, and Playmakers of the Translational Regenerative Medicine.

Since their first isolation and characterization by Friedenstein et al. in 1974 [1], mesenchymal stem cells (MSCs) were proven essential for tissue regeneration and homeostasis

Metabolic reprograming of mononuclear phagocytes in progressive multiple sclerosis.

UNLABELLED: Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). Accumulation of brain damage in progressive MS is partly the result of mononuclear phagocytes (MPs) attacking myelin sheaths in the CNS. Although there is no cure yet for MS, significant advances have been made in the development of disease modifying agents. Unfortunately, most of these drugs fail to reverse established neurological deficits and can have adverse effects. Recent evidence suggests that MPs polarization is accompanied by profound metabolic changes, whereby pro-inflammatory MPs (M1) switch toward glycolysis, whereas anti-inflammatory MPs (M2) become more oxidative. It is therefore possible that reprograming MPs metabolism could affect their function and repress immune cell activation. This mini review describes the metabolic changes underpinning macrophages polarization and anticipates how metabolic re-education of MPs could be used for the treatment of MS. KEY POINTS: Inflammation in progressive MS is mediated primarily by MPs.Cell metabolism regulates the function of MPs.DMAs can re-educate the metabolism of MPs to promote healing

Stem Cells of the Aging Brain.

The adult central nervous system (CNS) contains resident stem cells within specific niches that maintain a self-renewal and proliferative capacity to generate new neurons, astrocytes, and oligodendrocytes throughout adulthood. Physiological aging is associated with a progressive loss of function and a decline in the self-renewal and regenerative capacities of CNS stem cells. Also, the biggest risk factor for neurodegenerative diseases is age, and current in vivo and in vitro models of neurodegenerative diseases rarely consider this. Therefore, combining both aging research and appropriate interrogation of animal disease models towards the understanding of the disease and age-related stem cell failure is imperative to the discovery of new therapies. This review article will highlight the main intrinsic and extrinsic regulators of neural stem cell (NSC) aging and discuss how these factors impact normal homeostatic functions within the adult brain. We will consider established in vivo animal and in vitro human disease model systems, and then discuss the current and future trajectories of novel senotherapeutics that target aging NSCs to ameliorate brain disease

The neural stem cell secretome and its role in brain repair.

Compelling evidence from experimental animal disease models and early-phase clinical trials identifies the transplantation of neural progenitor/stem cells (NSCs) as a viable path towards the development of clinically applicable exogenous stem cell therapies. Building from current advances in the field of NSC biology and following the positive outcomes of NSC transplantation studies, the contemporary view is that transplanted NSCs act as local 'factories' capable of producing and secreting a wide array of immune and neurotrophic factors. This has launched a 'stem cell race' to identify the mechanisms behind stem-cell mediated repair in what has been labeled the paracrine hypothesis. This hypothesis proposes that NSC grafts act as a natural source of potent biologics capable of modulating and promoting the restoration of several key functions in the central nervous system (CNS) tissue following acute or chronic tissue damage. Investigators have been inspired to examine novel ways to harness and utilize the pro-regenerative properties of NSC therapies as an alternative approach to a more classical (small molecule based) treatment of CNS diseases. In this review, we will discuss the most recent findings of human NSC (hNSCs) transplants in experimental animal models of CNS diseases that identify of hNSC-secreted factors, including those trafficked within extracellular membrane vesicles (EVs), and the outcomes of recent clinical trials utilizing hNSC therapeutics in CNS diseases

Metabolic Control of Smoldering Neuroinflammation.

Compelling evidence exists that patients with chronic neurological conditions, which includes progressive multiple sclerosis, display pathological changes in neural metabolism and mitochondrial function. However, it is unknown if a similar degree of metabolic dysfunction occurs also in non-neural cells in the central nervous system. Specifically, it remains to be clarified (i) the full extent of metabolic changes in tissue-resident microglia and infiltrating macrophages after prolonged neuroinflammation (e.g., at the level of chronic active lesions), and (ii) whether these alterations underlie a unique pathogenic phenotype that is amenable for therapeutic targeting. Herein, we discuss how cell metabolism and mitochondrial function govern the function of chronic active microglia and macrophages brain infiltrates and identify new metabolic targets for therapeutic approaches aimed at reducing smoldering neuroinflammation