Human Adipose-Derived Mesenchymal Stem Cells in Cell Therapy: Safety and Feasibility in Different "Hospital Exemption" Clinical Applications

Based on immunomodulatory, osteogenic, and pro-angiogenic properties of adipose-derived stem cells (ASCs), this study aims to assess the safety and efficacy of ASC-derived cell therapies for clinical indications. Two autologous ASC-derived products were proposed to 17 patients who had not experienced any success with conventional therapies: (1) a scaffold-free osteogenic three-dimensional graft for the treatment of bone non-union and (2) a biological dressing for dermal reconstruction of non-healing chronic wounds. Safety was studied using the quality control of the final product (genetic stability, microbiological/mycoplasma/endotoxin contamination) and the in vivo evaluation of adverse events after transplantation. Feasibility was assessed by the ability to reproducibly obtain the final ASC-based product with specific characteristics, the time necessary for graft manufacturing, the capacity to produce enough material to treat the lesion, the surgical handling of the graft, and the ability to manufacture the graft in line with hospital exemption regulations. For 16 patients (one patient did not undergo grafting because of spontaneous bone healing), in-process controls found no microbiological/mycoplasma/endotoxin contamination, no obvious deleterious genomic anomalies, and optimal ASC purity. Each type of graft was reproducibly obtained without significant delay for implantation and surgical handling was always according to the surgical procedure and the implantation site. No serious adverse events were noted for up to 54 months. We demonstrated that autologous ASC transplantation can be considered a safe and feasible therapy tool for extreme clinical indications of ASC properties and physiopathology of disease.     

L'espace minéral au Paléolithique moyen dans le Sud du Massif central : premiers résultats pétroarchéologiques

The Middle Palaeolithic mineral environment in the South of the Massif Central: preliminary petroarchaeological results. Five Middle-Palaeolithic assemblages coming from archaeological sites in the Haute-Loire and Ardèche dated to isotopic stages 7 to 5 have been studied using a petroarchaeological method based on the optimization of observation techniques at different scales with respect to genetic and postgenetic characteristics of flint raw materials. The method reveals a relatively large collection area for the middle mountain sites (Sainte-Anne I, Baume-Vallée, Le Rond-de-Saint-Arcons, Rochelimagne), but apparently a smaller one for the site of Payre, located nearby the side of the Rhône Valley. For all sites, gathering is predominantly local, but some distant sources are utilised too. The rare exogenous materials, for example the Bedoulian flint from Ardèche identified in the Velay assemblages (Sainte-Anne I, Baume-Vallée) are in fact located in the heart of the massif as well as in secondary deposits and thus do not allow one to establish firm circulation routes for, or certain contact between the relevant human groups. To cite this article: P. Fernandes et al., C. R. Palevol 5 (2006).     

Moth pollination of woody species in the Cerrados of Central Brazil: a case of so much owed to so few?

We present a survey of moth pollination in woody species of the Cerrado of Central Brazil. Although with the exception of Roupala montana (which has simple polysepalous flowers arranged in dense cymes) all moth pollinated species in this community have tubular flowers, or a pseudo-tube formed from a single folded petal in Qualea grandiflora, settling moth flowers (tube less than 15 mm) vs. hawkmoth flowers (tube more than 50 mm) are markedly different in size. Moths visit some 20 woody Cerrado species, but they are probably effective pollinators of only 13 species or ca.14% of the woody taxa studied, and even in these latter species they are often very sparse visitors. Nevertheless, it is notable that moths are pollinators for 21% of the 38 most commonly distributed woody Cerrado species. Moreover, the reproductive efficacy of the studied moth pollinated species was similar to that of species pollinated by other kind of vectors.     

Framing the Salmonidae Family Phylogenetic Portrait: A More Complete Picture from Increased Taxon Sampling

Considerable research efforts have focused on elucidating the systematic relationships among salmonid fishes; an understanding of these patterns of relatedness will inform conservation- and fisheries-related issues, as well as provide a framework for investigating evolutionary mechanisms in the group. However, uncertainties persist in current Salmonidae phylogenies due to biological and methodological factors, and a comprehensive phylogeny including most representatives of the family could provide insight into the causes of these difficulties. Here we increase taxon sampling by including nearly all described salmonid species (n = 63) to present a time-calibrated and more complete portrait of Salmonidae using a combination of molecular markers and analytical techniques. This strategy improved resolution by increasing the signal-to-noise ratio and helped discriminate methodological and systematic errors from sources of difficulty associated with biological processes. Our results highlight novel aspects of salmonid evolution. First, we call into question the widely-accepted evolutionary relationships among sub-families and suggest that Thymallinae, rather than Coregoninae, is the sister group to the remainder of Salmonidae. Second, we find that some groups in Salmonidae are older than previously thought and that the mitochondrial rate of molecular divergence varies markedly among genes and clades. We estimate the age of the family to be 59.1 MY (CI: 63.2-58.1 MY) old, which likely corresponds to the timing of whole genome duplication in salmonids. The average, albeit highly variable, mitochondrial rate of molecular divergence was estimated as ∼0.31%/MY (CI: 0.27–0.36%/MY). Finally, we suggest that some species require taxonomic revision, including two monotypic genera, Stenodus and Salvethymus. In addition, we resolve some relationships that have been notoriously difficult to discern and present a clearer picture of the evolution of the group. Our findings represent an important contribution to the systematics of Salmonidae, and provide a useful tool for addressing questions related to fundamental and applied evolutionary issues.     

A CUG codon adapted two-hybrid system for the pathogenic fungus Candida albicans

The genetics of the most common human pathogenic fungus Candida albicans has several unique characteristics. Most notably, C. albicans does not follow the universal genetic code, by translating the CUG codon into serine instead of leucine. Consequently, the use of Saccharomyces cerevisiae as a host for yeast two-hybrid experiments with C. albicans proteins is limited due to erroneous translation caused by the aberrant codon usage of C. albicans. To circumvent the need for heterologous expression and codon optimalization of C. albicans genes we constructed a two-hybrid system with C. albicans itself as the host with components that are compatible for use in this organism. The functionality of this two-hybrid system was shown by successful interaction assays with the protein pairs Kis1–Snf4 and Ino4-Ino2. We further confirmed interactions between components of the filamentation/mating MAP kinase pathway, including the unsuspected interaction between the MAP kinases Cek2 and Cek1. We conclude that this system can be used to enhance our knowledge of protein–protein interactions in C. albicans.     

Force to Divide: Structural and Mechanical Requirements for Actomyosin Ring Contraction

One of the unresolved questions in the field of cell division is how the actomyosin cytoskeleton remains structurally organized while generating the contractile force to divide one cell into two. In analogy to the actomyosin-based force production mechanism in striated muscle, it was originally proposed that contractile stress in the actomyosin ring is generated via a sliding filament mechanism within an organized sarcomere-like array. However, over the last 30 years, ultrastructural and functional studies have noted important distinctions between cytokinetic structures in dividing cells and muscle sarcomeres. Myosin-II motor activity is not always required, and there is evidence that actin depolymerization contributes to contraction. In this Review, the architecture and contractile dynamics of the actomyosin ring at the cell division plane will be discussed. We will report the interdisciplinary advances in the field as well as their integration into a mechanistic understanding of contraction in cell division and in other biological processes that rely on an actomyosin-based force-generating system.