Magnetic resonance imaging of experimental autoimmune encephalomyelitis in the common marmoset.

Magnetic resonance imaging (MRI) is an invaluable tool for the diagnosis and monitoring of patients with multiple sclerosis (MS) as well as for the study of the disease pathophysiology. Because of its strong clinical, radiological and histopathological similarities with the human disease, experimental autoimmune encephalomyelitis (EAE) in the common marmoset has been studied more intensively over the past several years. Here, we review the current knowledge on MRI in the marmoset EAE, and we outline the physiopathological significance and translational values of these studies with respect to MS. Accumulating evidences suggest that the application of conventional, as well as non-conventional, MRI techniques in the marmoset EAE is a promising approach to elucidate the pathological processes underlying the development of inflammatory demyelinated lesions in the central nervous system, potentially improving the identification and development of new therapeutics

The GENIUS Grid Portal and robot certificates: a new tool for e-Science

<p>Abstract</p> <p>Background</p> <p>Grid technology is the computing model which allows users to share a wide <it>pletora </it>of distributed computational resources regardless of their geographical location. Up to now, the high security policy requested in order to access distributed computing resources has been a rather big limiting factor when trying to broaden the usage of Grids into a wide community of users. Grid security is indeed based on the Public Key Infrastructure (PKI) of X.509 certificates and the procedure to get and manage those certificates is unfortunately not straightforward. A first step to make Grids more appealing for new users has recently been achieved with the adoption of robot certificates.</p> <p>Methods</p> <p>Robot certificates have recently been introduced to perform automated tasks on Grids on behalf of users. They are extremely useful for instance to automate grid service monitoring, data processing production, distributed data collection systems. Basically these certificates can be used to identify a person responsible for an unattended service or process acting as client and/or server. Robot certificates can be installed on a smart card and used behind a portal by everyone interested in running the related applications in a Grid environment using a user-friendly graphic interface. In this work, the GENIUS Grid Portal, powered by EnginFrame, has been extended in order to support the new authentication based on the adoption of these robot certificates.</p> <p>Results</p> <p>The work carried out and reported in this manuscript is particularly relevant for all users who are not familiar with personal digital certificates and the technical aspects of the Grid Security Infrastructure (GSI). The valuable benefits introduced by robot certificates in e-Science can so be extended to users belonging to several scientific domains, providing an asset in raising Grid awareness to a wide number of potential users.</p> <p>Conclusion</p> <p>The adoption of Grid portals extended with robot certificates, can really contribute to creating transparent access to computational resources of Grid Infrastructures, enhancing the spread of this new paradigm in researchers' working life to address new global scientific challenges. The evaluated solution can of course be extended to other portals, applications and scientific communities.</p

Toxoplasmosis in Kosovo pregnant women

This study presents the initial results of a collaborative project aimed at the evaluation of Toxoplasma seroprevalence in a population of Kosovar pregnant women. The serum samples of 334 pregnant women were tested to detect IgG, IgM, IgG avidity for toxoplasmosis. Data regarding age, occupation, area of origin and education were also obtained for the pregnant women examined; 97/334 (29.4%) resulted positive for IgG antibodies, four of whom (4.1%) were also positive for IgM, (1.2% of the total population examined). All four IgM-positive pregnant women also demonstrated low avidity tests. The rate of IgG seroprevalence found in our study was lower than that observed in various European countries, especially those of western Europe. Conversely, the percentage of recent infections was higher than expected. The higher rate of infections could be the result of a recent toxoplasmosis epidemic in Kosovo, most likely due to the altered hygienic conditions caused by the forced transfer of the ethnic-Albanian population from an area of low (Serbia) to high (Kosovo) toxoplasmosis prevalence

Glibenclamide Mimics Metabolic Effects of Metformin in H9c2 Cells

BACKGROUND: Sulfonylureas, such as glibenclamide, are antidiabetic drugs that stimulate beta-cell insulin secretion by binding to the sulfonylureas receptors (SURs) of adenosine triphosphate-sensitive potassium channels (KATP). Glibenclamide may be also cardiotoxic, this effect being ascribed to interference with the protective function of cardiac KATP channels for which glibenclamide has high affinity. Prompted by recent evidence that glibenclamide impairs energy metabolism of renal cells, we investigated whether this drug also affects the metabolism of cardiac cells. METHODS: The cardiomyoblast cell line H9c2 was treated for 24 h with glibenclamide or metformin, a known inhibitor of the mitochondrial respiratory chain. Cell viability was evaluated by sulforodhamine B assay. ATP and AMP were measured according to the enzyme coupling method and oxygen consumption by using an amperometric electrode, while Fo-F1 ATP synthase activity assay was evaluated by chemiluminescent method. Protein expression was measured by western blot. RESULTS: Glibenclamide deregulated energy balance of H9c2 cardiomyoblasts in a way similar to that of metformin. It inhibited mitochondrial complexes I, II and III with ensuing impairment of oxygen consumption and ATP synthase activity, ATP depletion and increased AMPK phosphorylation. Furthermore, glibenclamide disrupted mitochondrial subcellular organization. The perturbation of mitochondrial energy balance was associated with enhanced anaerobic glycolysis, with increased activity of phosphofructo kinase, pyruvate kinase and lactic dehydrogenase. Interestingly, some additive effects of glibenclamide and metformin were observed. CONCLUSIONS: Glibenclamide deeply alters cell metabolism in cardiac cells by impairing mitochondrial organization and function. This may further explain the risk of cardiovascular events associated with the use of this drug, alone or in combination with metformin

TTV and other anelloviruses: The astonishingly wide spread of a viral infection

The broad family of viruses known as anelloviruses (AV) infects both humans and numerous animal species. They have a tiny, covalently closed single-stranded DNA genome and the astonishing capacity to infect a very high percentage of healthy and ill people with chronic infections that could last a lifetime. AV, and particularly the prototype Torquetenovirus, have established a successful interaction with the host's immune system and the rate at which they replicate is a gauge to measure overall immune function, even though many aspects of their life cycle and pathogenesis are still poorly understood

Mechanisms of diffusion of radon in buildings and mitigation techniques

Radon is a naturally occurring radioactive gas found in rocks, soil, and building materials. Precisely because of its gaseous nature, it tends to concentrate in indoor environments, resulting in a danger to human health. The effects of radon have been described, documented, and attested by the international scientific community and recognized as the second cause of lung cancer after cigarette smoking and in synergy with it. In December 2013, the Council of the European Union issued Council Directive 2013/59/Euratom, which establishes basic safety standards relating to protection against the dangers deriving from exposure to ionized radiation and managing the health risks associated with radon. In addition, designing buildings against radon risk in synergy with the use of low environmental impact materials is one of the objectives of building sustainability certifications. This work presents how radon creeps into buildings and reports several technologies that are needed to remove and mitigate the risk associated with indoor radon in existing and new buildings

A multidisciplinary approach to study a couple of monozygotic twins discordant for the chronic fatigue syndrome: a focus on potential salivary biomarkers

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a severe, systemic illness characterized by persistent, debilitating and medically unexplained fatigue. The etiology and pathophysiology of CFS remains obscure, and diagnosis is formulated through the patient’s history and exclusion of other medical causes. Thereby, the availability of biomarkers for CFS could be useful for clinical research. In the present study, we used a proteomic approach to evaluate the global changes in the salivary profile in a couple of monozygotic twins who were discordant for CFS. The aim was to evaluate differences of salivary protein expression in the CFS patient in respect to his healthy twin. METHODS: Saliva samples were submitted to two-dimensional electrophoresis (2DE). The gels were stained with Sypro, and a comparison between CFS subject and the healthy one was performed by the software Progenesis Same Spot including the Analysis of variance (ANOVA test). The proteins spot found with a ≥2-fold spot quantity change and p<0.05 were identified by Nano-liquid chromatography electrospray ionization tandem mass spectrometry. To validate the expression changes found with 2DE of 5 proteins (14-3-3 protein zeta/delta, cyclophilin A, Cystatin-C, Protein S100-A7, and zinc-alpha-2-glycoprotein), we used the western blot analysis. Moreover, proteins differentially expressed were functionally analyzed using the Ingenuity Pathways Analysis software with the aim to determine the predominant canonical pathways and the interaction network involved. RESULTS: The analysis of the protein profiles allowed us to find 13 proteins with a different expression in CFS in respect to control. Nine spots were up-regulated in CFS and 4 down-regulated. These proteins belong to different functional classes, such as inflammatory response, immune system and metabolism. In particular, as shown by the pathway analysis, the network built with our proteins highlights the involvement of inflammatory response in CFS pathogenesis. CONCLUSIONS: This study shows the presence of differentially expressed proteins in the saliva of the couple of monozygotic twins discordant for CFS, probably related to the disease. Consequently, we believe the proteomic approach could be useful both to define a panel of potential diagnostic biomarkers and to shed new light on the comprehension of the pathogenetic pathways of CFS

Novel Marmoset (Callithrix jacchus) Model of Human Herpesvirus 6A and 6B Infections: Immunologic, Virologic and Radiologic Characterization

Human Herpesvirus 6 (HHV-6) is a ubiquitous virus with an estimated seroprevalence of 95% in the adult population. HHV-6 is associated with several neurologic disorders, including multiple sclerosis, an inflammatory demyelinating disease affecting the CNS. Animal models of HHV-6 infection would help clarify its role in human disease but have been slow to develop because rodents lack CD46, the receptor for cellular entry. Therefore, we investigated the effects of HHV-6 infections in a non-human primate, the common marmoset Callithrix jacchus. We inoculated a total of 12 marmosets with HHV-6A and HHV-6B intravenously and HHV-6A intranasally. Animals were monitored for 25 weeks post-inoculation clinically, immunologically and by MRI. Marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms and generated virus-specific antibody responses, while those inoculated intravenously with HHV-6B were asymptomatic and generated comparatively lower antibody responses. Viral DNA was detected at a low frequency in paraffin-embedded CNS tissue of a subset of marmosets inoculated with HHV-6A and HHV-6B intravenously. When different routes of HHV-6A inoculation were compared, intravenous inoculation resulted in virus-specific antibody responses and infrequent detection of viral DNA in the periphery, while intranasal inoculation resulted in negligible virus-specific antibody responses and frequent detection of viral DNA in the periphery. Moreover, marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms, while marmosets inoculated with HHV-6A intranasally were asymptomatic. We demonstrate that a marmoset model of HHV-6 infection can serve to further define the contribution of this ubiquitous virus to human neurologic disorders