Alginate Scaffolds for Mesenchymal Stem Cell Cardiac Therapy: Influence of Alginate Composition

Despite the success of alginate scaffolds and mesenchymal stem cells (MSCs) therapy in cardiac failure treatment, the impact of the physicochemical environment provided by alginate matrices on cell behavior has never been investigated. The purpose of this work was double: to determine the alginate composition influence on (1) encapsulated rat MSC viability, paracrine activity, and phenotype in vitro and (2) cardiac implantability and in vivo biocompatibility of patch shape scaffolds. Two alginates, differing in composition and thus presenting different mechanical properties when hydrogels, were characterized. In both cases, encapsulated MSC viability was maintained at around 75%, and their secretion characteristics were retained 28 days postencapsulation. In vivo study revealed a high cardiac compatibility of the tested alginates: cardiac parameters were maintained, and rats did not present any sign of infection. Moreover, explanted hydrogels appeared surrounded by a vascularized tissue. However, scaffold implantability was highly dependent on alginate composition. G-type alginate patches, presenting higher elastic and Young moduli than M-type alginate patches, showed a better implantation easiness and were the only ones that maintained their shape and morphology in vivo. As a consequence of alginate chemical composition and resulting hydrogel structuration, G-type alginate hydrogels appear to be more adapted for cardiac implantation

Oxidative inactivation of NiFeSe hydrogenase

International audienceWe propose a resolution to the paradox that spectroscopic studies of NiFeSe hydrogenase have not revealed any major signal attributable to NiIII states formed upon reaction with O2, despite the fact that two inactive states are formed upon either aerobic or anaerobic oxidation

The demand for money in developing countries: Assessing the role of financial innovation

Traditional specifications of money demand have been commonly plagU4:!d by persistent overprediction, implausible parameter estimates, and highly autocorrelated errors. This paper argues that some of those problems stem from the failure to account for the impact of financial innovation. We estimate money demand for ten developing countries employing various proxies for the innovation process and provide an assessment of the relative importance of this variable. We find that financial innovation plays an important role in determining money demand and its fluctuations, and that the importance of this role increases with the rate of inflation.

Elaboration and evaluation of alginate foam scaffolds for soft tissue engineering

Controlling microarchitecture in polymer scaffolds is a priority in material design for soft tissue applications. This paper reports for the first time the elaboration of alginate foam-based scaffolds for mesenchymal stem cell (MSC) delivery and a comparative study of various surfactants on the final device performance. The use of surfactants permitted to obtain highly interconnected porous scaffolds with tunable pore size on surface and in cross-section. Their mechanical properties in compression appeared to be adapted to soft tissue engineering. Scaffold structures could sustain MSC proliferation over 14 days. Paracrine activity of scaffold-seeded MSCs varied with the scaffold structure and growth factors release was globally improved in comparison with control alginate scaffolds. Our results provide evidence that exploiting different surfactant types for alginate foam preparation could be an original method to obtain biocompatible scaffolds with tunable architecture for soft tissue engineering

CEST: a Cognitive Event based Semi-automatic Technique for behavior segmentation

This work introduces CEST, a Cognitive Event based Semiautomatic Technique for behavior segmentation. The technique was inspired by an everyday cognitive process. Humans, in fact, make sense of what happens to them by breaking the continuous stream of activity into smaller units, through a process known as segmentation. A cognitive theory, the Event Segmentation Theory, provides a computational and neurophysiological account of this process, describing how the detection of changes in the current situation drive boundary perception. CEST was designed with the aim of providing affective researchers with a tool to semi-automatically segment behavior. Researchers investigating behavior, as a matter of fact, often need to parse their research data into simpler units, either manually or automatically. To perform segmentation, the technique combines manual annotations and the output of change-point detection algorithms, techniques from time-series research that afford the detection of abrupt changes in time-series. CEST is inherently multidisciplinary: it is, to the best of our knowledge, the first attempt to adopt a cognitive science perspective on the issue of (semi) automatic behavior segmentation. CEST is a general-purpose technique, as it aims at providing a tool for segmenting behavior across research areas. In this manuscript, we detail the theories behind the design of CEST and the results of two experimental studies aimed at assessing the feasibility of the approach on both single and group scenarios. Most importantly, we present the results of the evaluation of CEST on a data-set of dance performances. We explore seven different techniques for change-point detection that could be leveraged to achieve semi-automatic segmentation through CEST and illustrate how two different bayesian algorithms led to the highest scores. Upon selecting the best algorithms, we measured the effect of the temporal grain of the analysis on the performance. Overall, our results support the idea of a semiautomatic segmentation technique for behavior segmentation. The output of the analysis mirrors cognitive science research on segmentation and on event structure perception. The work also tackles new challenges that may arise from our approach

Evaluation of polyelectrolyte complex-based scaffolds for mesenchymal stem cell therapy in cardiac ischemia treatment

Three-dimensional (3D) scaffolds hold great potential for stem cell-based therapies. Indeed, recent results have shown that biomimetic scaffolds may enhance cell survival and promote an increase in the concentration of therapeutic cells at the injury site. The aim of this work was to engineer an original polymeric scaffold based on the respective beneficial effects of alginate and chitosan. Formulations were made from various alginate/chitosan ratios to form opposite-charge polyelectrolyte complexes (PECs). After freeze-drying, the resultant matrices presented a highly interconnected porous microstructure and mechanical properties suitable for cell culture. In vitro evaluation demonstrated their compatibility with mesenchymal stell cell (MSC) proliferation and their ability to maintain paracrine activity. Finally, the in vivo performance of seeded 3D PEC scaffolds with a polymeric ratio of 40/60 was evaluated after an acute myocardial infarction provoked in a rat model. Evaluation of cardiac function showed a significant increase in the ejection fraction, improved neovascularization, attenuated fibrosis as well as less left ventricular dilatation as compared to an animal control group. These results provide evidence that 3D PEC scaffolds prepared from alginate and chitosan offer an efficient environment for 3D culturing of MSCs and represent an innovative solution for tissue engineering

Integrating DNA damage repair with the cell cycle

Abstract DNA is labile and constantly subject to damage. In addition to external mutagens, DNA is continuously damaged by the aqueous environment, cellular metabolites and is prone to strand breakage during replication. Cell duplication is orchestrated by the cell division cycle and specific DNA structures are processed differently depending on where in the cell cycle they are detected. This is often because a specific structure is physiological in one context, for example during DNA replication, while indicating a potentially pathological event in another, such as interphase or mitosis. Thus, contextualising the biochemical entity with respect to cell cycle progression provides information necessary to appropriately regulate DNA processing activities. We review the links between DNA repair and cell cycle context, drawing together recent advances

A route to new cancer therapies:the FA pathway is essential in BRCA1- or BRCA2-deficient cells

Mutations in the BRCA1 and BRCA2 genes strongly predispose carriers to breast and ovarian cancers. Two new studies reveal that FANCD2, a key component of the Fanconi anemia pathway, is essential for the survival of cells with BRCA1 or BRCA2 mutations. These findings pave the way for new 'synthetic lethal' strategies to kill BRCA-mutated cancers.<br/

Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair.

Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification