Mesenchymal stem cells and their use as cell replacement therapy and disease modelling tool.

Mesenchymal stem cells (MSCs) from adult somatic tissues may differentiate in vitro and in vivo into multiple mesodermal tissues including bone, cartilage, adipose tissue, tendon, ligament or even muscle. MSCs preferentially home to damaged tissues where they exert their therapeutic potential. A striking feature of the MSCs is their low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes and antigen-presenting cells. Instead, MSCs appear to be immunosuppressive in vitro. Their multilineage differentiation potential coupled to their immuno-privileged properties is being exploited worldwide for both autologous and allogeneic cell replacement strategies. Here, we introduce the readers to the biology of MSCs and the mechanisms underlying immune tolerance. We then outline potential cell replacement strategies and clinical applications based on the MSCs immunological properties. Ongoing clinical trials for graft-versus-host-disease, haematopoietic recovery after co-transplantation of MSCs along with haematopoietic stem cells and tissue repair are discussed. Finally, we review the emerging area based on the use of MSCs as a target cell subset for either spontaneous or induced neoplastic transformation and, for modelling non-haematological mesenchymal cancers such as sarcomas

Transcriptomic Characterization of a Synergistic Genetic Interaction during Carpel Margin Meristem Development in Arabidopsis thaliana

In flowering plants the gynoecium is the female reproductive structure. In Arabidopsis thaliana ovules initiate within the developing gynoecium from meristematic tissue located along the margins of the floral carpels. When fertilized the ovules will develop into seeds. SEUSS (SEU) and AINTEGUMENTA (ANT) encode transcriptional regulators that are critical for the proper formation of ovules from the carpel margin meristem (CMM). The synergistic loss of ovule initiation observed in the seu ant double mutant suggests that SEU and ANT share overlapping functions during CMM development. However the molecular mechanism underlying this synergistic interaction is unknown. Using the ATH1 transcriptomics platform we identified transcripts that were differentially expressed in seu ant double mutant relative to wild type and single mutant gynoecia. In particular we sought to identify transcripts whose expression was dependent on the coordinated activities of the SEU and ANT gene products. Our analysis identifies a diverse set of transcripts that display altered expression in the seu ant double mutant tissues. The analysis of overrepresented Gene Ontology classifications suggests a preponderance of transcriptional regulators including multiple members of the REPRODUCTIVE MERISTEMS (REM) and GROWTH-REGULATING FACTOR (GRF) families are mis-regulated in the seu ant gynoecia. Our in situ hybridization analyses indicate that many of these genes are preferentially expressed within the developing CMM. This study is the first step toward a detailed description of the transcriptional regulatory hierarchies that control the development of the CMM and ovule initiation. Understanding the regulatory hierarchy controlled by SEU and ANT will clarify the molecular mechanism of the functional redundancy of these two genes and illuminate the developmental and molecular events required for CMM development and ovule initiation

Plasticity of the β-Trefoil Protein Fold in the Recognition and Control of Invertebrate Predators and Parasites by a Fungal Defence System

Discrimination between self and non-self is a prerequisite for any defence mechanism; in innate defence, this discrimination is often mediated by lectins recognizing non-self carbohydrate structures and so relies on an arsenal of host lectins with different specificities towards target organism carbohydrate structures. Recently, cytoplasmic lectins isolated from fungal fruiting bodies have been shown to play a role in the defence of multicellular fungi against predators and parasites. Here, we present a novel fruiting body lectin, CCL2, from the ink cap mushroom Coprinopsis cinerea. We demonstrate the toxicity of the lectin towards Caenorhabditis elegans and Drosophila melanogaster and present its NMR solution structure in complex with the trisaccharide, GlcNAcβ1,4[Fucα1,3]GlcNAc, to which it binds with high specificity and affinity in vitro. The structure reveals that the monomeric CCL2 adopts a β-trefoil fold and recognizes the trisaccharide by a single, topologically novel carbohydrate-binding site. Site-directed mutagenesis of CCL2 and identification of C. elegans mutants resistant to this lectin show that its nematotoxicity is mediated by binding to α1,3-fucosylated N-glycan core structures of nematode glycoproteins; feeding with fluorescently labeled CCL2 demonstrates that these target glycoproteins localize to the C. elegans intestine. Since the identified glycoepitope is characteristic for invertebrates but absent from fungi, our data show that the defence function of fruiting body lectins is based on the specific recognition of non-self carbohydrate structures. The trisaccharide specifically recognized by CCL2 is a key carbohydrate determinant of pollen and insect venom allergens implying this particular glycoepitope is targeted by both fungal defence and mammalian immune systems. In summary, our results demonstrate how the plasticity of a common protein fold can contribute to the recognition and control of antagonists by an innate defence mechanism, whereby the monovalency of the lectin for its ligand implies a novel mechanism of lectin-mediated toxicity

Geographic variations of the prevalence and distribution of COPD phenotypes in Spain: “the ESPIRAL-ES study”

Bernardino Alcázar-Navarrete,1 Juan Antonio Trigueros,2 Juan Antonio Riesco,3,4 Anna Campuzano,5 Joselín Pérez5 1Pulmonology Department, Hospital La Loja, Granada, 2Centro de Salud de Menasalvas, Toledo, 3Pulmonology Department, Hospital San Pedro de Alcántara, 4Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Cáceres, 5Grupo Ferrer Internacional, Barcelona, Spain Purpose: The purpose of this study was to assess the prevalence of COPD phenotypes at a national level and to determine their geographic distribution among different autonomous communities in Spain. Patients and methods: A total of 1,610 patients (82% men, median age 67 years) recruited in primary care centers and pneumology services participated in an observational, cross-sectional, and multicenter study. Phenotypes evaluated were the non-exacerbator phenotype, the asthma–COPD overlap syndrome (ACOS), the exacerbator phenotype with emphysema, and the exacerbator phenotype with chronic bronchitis. Results: The non-exacerbator phenotype was the most common (46.7%) followed by exacerbator with chronic bronchitis (22.4%) and exacerbator with emphysema (16.4%). The ACOS phenotype accounted for the lowest rate (14.5%). For each phenotype, the highest prevalence rates were concentrated in two or three autonomous communities, with relatively similar rates for the remaining regions. Overall prevalence rates were higher for the non-exacerbator and the exacerbator with chronic bronchitis phenotypes than for ACOS and the exacerbator with chronic bronchitis phenotypes. Differences in the distribution of COPD phenotypes according to gender, age, physician specialty, smoking habit, number of comorbidities, quality of life assessed with the COPD Assessment Test, and BODEx index (body mass index, airflow obstruction, dyspnea, and exacerbations) were all statistically significant. Conclusion: Differences in the prevalence rates of COPD phenotypes among the Spanish autonomous communities have been documented. Mapping the distribution of COPD phenotypes is useful to highlight regional differences as starting point for comparisons across time. This geographic analysis provides health-care planners a valuable platform to assess changes in COPD burden at nationwide and regional levels. Keywords: pulmonary disease, chronic obstructive, phenotype, quality of lif

Mesenchymal stem cells and their use as cell replacement therapy and disease modelling tool.

Mesenchymal stem cells (MSCs) from adult somatic tissues may differentiate in vitro and in vivo into multiple mesodermal tissues including bone, cartilage, adipose tissue, tendon, ligament or even muscle. MSCs preferentially home to damaged tissues where they exert their therapeutic potential. A striking feature of the MSCs is their low inherent immunogenicity as they induce little, if any, proliferation of allogeneic lymphocytes and antigen-presenting cells. Instead, MSCs appear to be immunosuppressive in vitro. Their multilineage differentiation potential coupled to their immuno-privileged properties is being exploited worldwide for both autologous and allogeneic cell replacement strategies. Here, we introduce the readers to the biology of MSCs and the mechanisms underlying immune tolerance. We then outline potential cell replacement strategies and clinical applications based on the MSCs immunological properties. Ongoing clinical trials for graft-versus-host-disease, haematopoietic recovery after co-transplantation of MSCs along with haematopoietic stem cells and tissue repair are discussed. Finally, we review the emerging area based on the use of MSCs as a target cell subset for either spontaneous or induced neoplastic transformation and, for modelling non-haematological mesenchymal cancers such as sarcomas

Brucella spondylitis complicated by an infected abdominal aortic aneurysm and deep venous thrombosis: case report and review of the literature

Brucellosis is a common zoonosis, which still remains as a major health problem in certain parts of the world. Spondylodiscitis is the most frequent osteoarticular complication of brucellosis. Herein is reported an uncommon case of a middle-aged male treated for brucellosis who developed 2 years after the treatment brucellar spondylo-discitis complicated by a psoas muscle abscess, an infected abdominal aorta aneurysm and deep venous thrombosis of IVC, common iliac, external iliac and common femoral veins. CT and CT angiography were the imaging modalities depicting the findings. After an endovascular stent graft placement in abdominal aorta aneurysm, a CT guided drainage of retroperitoneal abscess revealed Brucella melitensis as the pathogen microorganism. Diagnosis of spondylodiscitis and contiguous psoas abscess is usually simple but aortic involvement is difficult to identify and can be easily overlooked. A high degree of suspicion is essential to reduce the delay for the treatment