Differential Gene Expression Profiling of Dystrophic Dog Muscle after MuStem Cell Transplantation

BackgroundSeveral adult stem cell populations exhibit myogenic regenerative potential, thus representing attractive candidates for therapeutic approaches of neuromuscular diseases such as Duchenne Muscular Dystrophy (DMD). We have recently shown that systemic delivery of MuStem cells, skeletal muscle-resident stem cells isolated in healthy dog, generates the remodelling of muscle tissue and gives rise to striking clinical benefits in Golden Retriever Muscular Dystrophy (GRMD) dog. This global effect, which is observed in the clinically relevant DMD animal model, leads us to question here the molecular pathways that are impacted by MuStem cell transplantation. To address this issue, we compare the global gene expression profile between healthy, GRMD and MuStem cell treated GRMD dog muscle, four months after allogenic MuStem cell transplantation.ResultsIn the dystrophic context of the GRMD dog, disease-related deregulation is observed in the case of 282 genes related to various processes such as inflammatory response, regeneration, calcium ion binding, extracellular matrix organization, metabolism and apoptosis regulation. Importantly, we reveal the impact of MuStem cell transplantation on several molecular and cellular pathways based on a selection of 31 genes displaying signals specifically modulated by the treatment. Concomitant with a diffuse dystrophin expression, a histological remodelling and a stabilization of GRMD dog clinical status, we show that cell delivery is associated with an up-regulation of genes reflecting a sustained enhancement of muscle regeneration. We also identify a decreased mRNA expression of a set of genes having metabolic functions associated with lipid homeostasis and energy. Interestingly, ubiquitin-mediated protein degradation is highly enhanced in GRMD dog muscle after systemic delivery of MuStem cells.ConclusionsOverall, our results provide the first high-throughput characterization of GRMD dog muscle and throw new light on the complex molecular/cellular effects associated with muscle repair and the clinical efficacy of MuStem cell-based therapy.     

Topology Analysis of Social Networks Extracted from Literature

In a world where complex networks are an increasingly important part of science, it is interesting to question how the new reading of social realities they provide applies to our cultural background and in particular, popular culture. Are authors of successful novels able to reproduce social networks faithful to the ones found in reality? Is there any common trend connecting an author’s oeuvre, or a genre of fiction? Such an analysis could provide new insight on how we, as a culture, perceive human interactions and consume media. The purpose of the work presented in this paper is to define the signature of a novel’s story based on the topological analysis of its social network of characters. For this purpose, an automated tool was built that analyses the dialogs in novels, identifies characters and computes their relationships in a time-dependent manner in order to assess the network’s evolution over the course of the story.     

Infectious Chikungunya Virus in the Saliva of Mice,Monkeys and Humans

Chikungunya virus (CHIKV) is a reemerging, ordinarily mosquito-transmitted, alphavirus that occasionally produces hemorrhagic manifestations, such as nose bleed and bleeding gums, in human patients. Interferon response factor 3 and 7 deficient (IRF3/7^-/-) mice, which are deficient for interferon α/β responses, reliably develop hemorrhagic manifestations after CHIKV infection. Here we show that infectious virus was present in the oral cavity of CHIKV infected IRF3/7^-/- mice, likely due to hemorrhagic lesions in the olfactory epithelium that allow egress of infected blood into the nasal, and subsequently, oral cavities. In addition, IRF3/7^-/- mice were more susceptible to infection with CHIKV via intranasal and oral routes, with IRF3/7^-/- mice also able to transmit virus mouse-to-mouse without an arthropod vector. Cynomolgus macaques often show bleeding gums after CHIKV infection, and analysis of saliva from several infected monkeys also revealed the presence of viral RNA and infectious virus. Furthermore, saliva samples collected from several acute CHIKV patients with hemorrhagic manifestations were found to contain viral RNA and infectious virus. Oral fluids can therefore be infectious during acute CHIKV infections, likely due to hemorrhagic manifestations in the oral/nasal cavities.     

Secondary metabolites of Bagassa guianensis Aubl. wood: A study of the chemotaxonomy of the Moraceae family

In order to explain the durability of the Moraceae plant family, phytochemistry of Bagassa guianensis was performed. Ethyl acetate extract was obtained from the heartwood and 18 secondary metabolites were isolated, including 6 moracins [6-O-methyl-moracin M, 6-O-methyl-moracin N and moracin Z; previously identified: moracin M, moracin N and moracin P], 8 stilbenoids [presently identified: (?)-epialboctalol and arachidin 4; previously identified: alboctalol, trans-resveratrol, arachidin 2, trans-oxyresveratrol and artogomezianol], 3 previously identified flavonoids, steppogenin, katuranin and dihydromorin, β-sitosterol and resorcinol. Previous studies suggest that stilbenoids are responsible for the natural durability of wood. Our study has determined that B. guianensis is closely related to Morus sp. in phylogeny and should be included in the Moreae sensu stricto tribe of the Moraceae family.     

The RASSF1A Tumor Suppressor Regulates XPA-Mediated DNA Repair

RASSF1A may be the most frequently inactivated tumor suppressor identified in human cancer so far. It is a proapoptotic Ras effector and plays an important role in the apoptotic DNA damage response (DDR). We now show that in addition to DDR regulation, RASSF1A also plays a key role in the DNA repair process itself. We show that RASSF1A forms a DNA damage-regulated complex with the key DNA repair protein xeroderma pigmentosum A (XPA). XPA requires RASSF1A to exert full repair activity, and RASSF1A-deficient cells exhibit an impaired ability to repair DNA. Moreover, a cancer-associated RASSF1A single-nucleotide polymorphism (SNP) variant exhibits differential XPA binding and inhibits DNA repair. The interaction of XPA with other components of the repair complex, such as replication protein A (RPA), is controlled in part by a dynamic acetylation/deacetylation cycle. We found that RASSF1A and its SNP variant differentially regulate XPA protein acetylation, and the SNP variant hyperstabilizes the XPA-RPA70 complex. Thus, we identify two novel functions for RASSF1A in the control of DNA repair and protein acetylation. As RASSF1A modulates both apoptotic DDR and DNA repair, it may play an important and unanticipated role in coordinating the balance between repair and death after DNA damage.     

Parkinsonism-associated Protein DJ-1/Park7 Is a Major Protein Deglycase That Repairs Methylglyoxal- and Glyoxal-glycated Cysteine,Arginine, and Lysine Residues

Glycation is an inevitable nonenzymatic covalent reaction between proteins and endogenous reducing sugars or dicarbonyls (methylglyoxal, glyoxal) that results in protein inactivation. DJ-1 was reported to be a multifunctional oxidative stress response protein with poorly defined function. Here, we show that human DJ-1 is a protein deglycase that repairs methylglyoxal- and glyoxal-glycated amino acids and proteins by acting on early glycation intermediates and releases repaired proteins and lactate or glycolate, respectively. DJ-1 deglycates cysteines, arginines, and lysines (the three major glycated amino acids) of serum albumin, glyceraldehyde-3-phosphate dehydrogenase, aldolase, and aspartate aminotransferase and thus reactivates these proteins. DJ-1 prevented protein glycation in an Escherichia coli mutant deficient in the DJ-1 homolog YajL and restored cell viability in glucose-containing media. These results suggest that DJ-1-associated Parkinsonism results from excessive protein glycation and establishes DJ-1 as a major anti-glycation and anti-aging protein.     

Canopy interactions and physical stress gradients in subtidal communities

Species interactions are integral drivers of community structure and can change from competitive to facilitative with increasing environmental stress. In subtidal marine ecosystems, however, interactions along physical stress gradients have seldom been tested. We observed seaweed canopy interactions across depth and latitudinal gradients to test whether light and temperature stress structured interaction patterns. We also quantified interspecific and intraspecific interactions among nine subtidal canopy seaweed species across three continents to examine the general nature of interactions in subtidal systems under low consumer pressure. We reveal that positive and neutral interactions are widespread throughout global seaweed communities and the nature of interactions can change from competitive to facilitative with increasing light stress in shallow marine systems. These findings provide support for the stress gradient hypothesis within subtidal seaweed communities and highlight the importance of canopy interactions for the maintenance of subtidal marine habitats experiencing environmental stress.     

Invasive alga <Emphasis Type="Italic">Caulerpa racemosa</Emphasis> var. <Emphasis Type="Italic">cylindracea</Emphasis> makes a strong impact on the Mediterranean sponge <Emphasis Type="Italic">Sarcotragus spinosulus</Emphasis>

Here we present the first observation of the impact of the invasive Caulerpa racemosa var. cylindracea on native photophilic sponge species in the Adriatic Sea, with special focus on Sarcotragus spinosulus. Caulerpa racemosa var. cylindracea is able to completely overgrow the sponge, developing an exceptionally thick canopy with a maximum measured density of 1,887 m of stolons m⁻² and 40,561 fronds m⁻². Necrosis of the sponge surface was significantly correlated with the algal dry biomass, frond number and stolon length. Dense algal canopy, penetration of the algal stolon and rhizoids into the sponge oscula and covering of the ostiae probably diminishes the seawater circulation through the sponge and consequently results in its smothering and even death. We suggest that chemotropism is the reason why C. racemosa penetrates the sponge oscula and establishes such dense canopy on the sponge.