60 research outputs found

    Novel Cell-Free Strategy for Therapeutic Angiogenesis: In Vitro Generated Conditioned Medium Can Replace Progenitor Cell Transplantation

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    BACKGROUND: Current evidence suggests that endothelial progenitor cells (EPC) contribute to ischemic tissue repair by both secretion of paracrine factors and incorporation into developing vessels. We tested the hypothesis that cell-free administration of paracrine factors secreted by cultured EPC may achieve an angiogenic effect equivalent to cell therapy. METHODOLOGY/PRINCIPAL FINDINGS: EPC-derived conditioned medium (EPC-CM) was obtained from culture expanded EPC subjected to 72 hours of hypoxia. In vitro, EPC-CM significantly inhibited apoptosis of mature endothelial cells and promoted angiogenesis in a rat aortic ring assay. The therapeutic potential of EPC-CM as compared to EPC transplantation was evaluated in a rat model of chronic hindlimb ischemia. Serial intramuscular injections of EPC-CM and EPC both significantly increased hindlimb blood flow assessed by laser Doppler (81.2+/-2.9% and 83.7+/-3.0% vs. 53.5+/-2.4% of normal, P<0.01) and improved muscle performance. A significantly increased capillary density (1.62+/-0.03 and 1.68+/-0.05/muscle fiber, P<0.05), enhanced vascular maturation (8.6+/-0.3 and 8.1+/-0.4/HPF, P<0.05) and muscle viability corroborated the findings of improved hindlimb perfusion and muscle function. Furthermore, EPC-CM transplantation stimulated the mobilization of bone marrow (BM)-derived EPC compared to control (678.7+/-44.1 vs. 340.0+/-29.1 CD34(+)/CD45(-) cells/1x10(5) mononuclear cells, P<0.05) and their recruitment to the ischemic muscles (5.9+/-0.7 vs. 2.6+/-0.4 CD34(+) cells/HPF, P<0.001) 3 days after the last injection. CONCLUSIONS/SIGNIFICANCE: Intramuscular injection of EPC-CM is as effective as cell transplantation for promoting tissue revascularization and functional recovery. Owing to the technical and practical limitations of cell therapy, cell free conditioned media may represent a potent alternative for therapeutic angiogenesis in ischemic cardiovascular diseases

    Response to Treatment and Disease Progression Linked to CD4+ T Cell Surface CC Chemokine Receptor 5 Density in Human Immunodeficiency Virus Type 1 Vertical Infection

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    The factors governing interindividual variability in disease progression among children vertically infected with human immunodeficiency virus type 1 (HIV-1) remain unclear. Because it has recently been shown in infected adults that the density of CC chemokine receptor 5 (CCR5) molecules at the surface of nonactivated (human leukocyte antigen [HLA]-DR-) CD4+ T cells correlates with disease progression, the same correlation was sought in children. HLA-DR-CD4+ T cell surface CCR5 density was constant over time and correlated with the bioclinical stage and with the CD4 cell slope observed before antiretroviral treatment. In addition, CCR5 density was negatively correlated with the intensity of the decrease in viremia during antiretroviral therapy and was positively correlated with CD4 cell slope since birth. These results are compatible with the hypothesis that CCR5 density is a key factor governing disease progression in pediatric HIV-1 infection and, thereby, an indicator of prognosis. Moreover, they suggest that therapies aimed at reducing CCR5 accessibility should slow down HIV disease evolution in childre

    Implementing Green Infrastructure for the Spatial Planning of Peri-Urban Areas in Geneva, Switzerland

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    The concept of green infrastructure (GI) seeks to identify and prioritize areas of high ecological value for wildlife and people, to improve the integration of natural values in landscape planning decisions. In 2018, the canton of Geneva, Switzerland, established a roadmap for biodiversity conservation, which includes the operationalization of GI covering 30% of the territory by 2030. In this paper, we demonstrate a GI mapping framework in the canton of Geneva. Our approach is based on the combined assessment of three 'pillars', namely species' distribution, landscape structure and connectivity, and ecosystem services, to optimize the allocation of conservation actions using the spatial prioritization software, Zonation. The identified priority conservation areas closely overlap existing natural reserves. Including the three pillars in the landscape prioritization should also improve adhesion to the GI idea, without undermining the protection of threatened species. With regards to land use planning, public and private land parcels with high values for GI may require specific incentives to maintain their desirable characteristics, as they are more likely to be degraded than areas with more building restrictions. Visualizing priority conservation areas in a spatially explicit manner will support decision-makers in Geneva to optimally allocate limited resources for ecosystem preservation.Peer reviewe

    The UV RESISTANCE LOCUS 8-Mediated UV-B Response Is Required Alongside CRYPTOCHROME 1 For Plant Survival Under Sunlight In Field Conditions

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    As sessile, photoautotrophic organisms, plants are subjected to fluctuating sunlight that includes potentially detrimental ultraviolet-B radiation (UV-B). Experiments under controlled conditions have shown that the UV-B photoreceptor UV RESISTANCE LOCUS 8 (UVR8) controls acclimation and tolerance to UV-B in Arabidopsis thaliana; however, its long-term impacts on plant fitness remain poorly understood in naturally fluctuating environments. Here we quantified the survival and reproduction of different Arabidopsis mutant genotypes in diverse field and laboratory conditions. We found that uvr8 mutants produced more fruits than wild type when grown in growth chambers under artificial low UV-B conditions but not in natural field conditions, indicating a fitness cost in absence of UV-B stress. Importantly, independent double mutants of UVR8 and the blue-light photoreceptor gene CRYPTOCHROME 1 (CRY1) in two genetic backgrounds showed a drastic reduction in fitness in the field. Experiments with UV-B attenuation experiments in field and with supplemental UV-B in growth chambers demonstrated that UV-B caused the conditional cry1 uvr8 lethality phenotype. Using RNA-seq data of field-grown single and double mutants, we explicitly identified genes showing statistical interaction of UVR8 and CRY1 mutations in the presence of UV-B in the field. They were enriched in Gene Ontology categories related to oxidative stress, photoprotection, and DNA damage repair in addition to UV-B response. Our study demonstrates the functional importance of the UVR8-mediated response across life stages in natura, which is partially redundant with that of cry1. Moreover, these data provide an integral picture of gene expression associated with plant responses under field conditions

    The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

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    The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article
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