Development of a + Cardiac Mouse Progenitor Immortalized Model to Unravel the Relationship with Its Protective Vascular Endothelial Niche.

The adult mammalian heart has been demonstrated to be endowed with low but real turnover capacity, especially for cardiomyocytes, the key functional cell type. The source, however, of that turnover capacity remains controversial. In this regard, we have defined and characterized a resident multipotent cardiac mouse progenitor population, +DR (for + Damage-Responsive cells).

Cardiac Progenitor Cell Exosomal miR-935 Protects against Oxidative Stress.

Oxidative stress-induced myocardial apoptosis and necrosis are critically involved in ischemic infarction, and several sources of extracellular vesicles appear to be enriched in therapeutic activities. The central objective was to identify and validate the differential exosome miRNA repertoire in human cardiac progenitor cells (CPC). CPC exosomes were first analyzed by LC-MS/MS and compared by RNAseq with exomes of human mesenchymal stromal cells and human fibroblasts to define their differential exosome miRNA repertoire (exo-miR).

Selection of phage-displayed antibodies with high affinity and specificity by electrophoresis in microfluidic devices.

A method development aimed for high-throughput and automated antibody screening holds great potential for areas ranging from fundamental molecular interactions to the discovery of novel disease markers, therapeutic targets, and monoclonal antibody engineering. Surface display techniques enable efficient manipulation of large molecular libraries in small volumes. Specifically, phage display appeared as a powerful technology for selecting peptides and proteins with enhanced, target-specific binding affinities.

High-rate activated sludge at very short SRT: Key factors for process stability and performance of COD fractions removal.

In high-rate activated sludge (HRAS) processes, reducing the solid retention time (SRT) minimizes COD oxidation and allows to obtain the maximum energy recovery. The aim of this research was to operate a pilot plant with an automatic control strategy to assure the HRAS process stability and high COD fractions removal at very low SRT. This study combines simulation and experimental tools (pilot plant 35 m·d  ) operating at SRT (0.

Comparative proteomic analysis of nuclear and cytoplasmic compartments in human cardiac progenitor cells.

Clinical trials evaluating cardiac progenitor cells (CPC) demonstrated feasibility and safety, but no clear functional benefits. Therefore a deeper understanding of CPC biology is warranted to inform strategies capable to enhance their therapeutic potential. Here we have defined, using a label-free proteomic approach, the differential cytoplasmic and nuclear compartments of human CPC (hCPC).

Fungal bioremediation of diuron-contaminated waters: Evaluation of its degradation and the effect of amendable factors on its removal in a trickle-bed reactor under non-sterile conditions.

The occurrence of the extensively used herbicide diuron in the environment poses a severe threat to the ecosystem and human health. Four different ligninolytic fungi were studied as biodegradation candidates for the removal of diuron. Among them, T.

The removal of diuron from agricultural wastewaters by Trametes versicolor immobilized on pinewood in simple channel reactors.

The presence of pesticides in agricultural wastewater entails harmful risks to both the environment and public health. In this study, two channel-type bioreactors with Trametes versicolor immobilized on pinewood chips were evaluated in terms of the removal efficiency of diuron from agricultural wastewater under non-sterile conditions. First, both single and successive sorption processes of diuron on pinewood chips were evaluated.

Exploring the degradation capability of Trametes versicolor on selected hydrophobic pesticides through setting sights simultaneously on culture broth and biological matrix.

Pesticides introduced inadvertently or deliberately into environment by global agricultural practices have caused growing public concern, therefore the search of approaches for elimination of such xenobiotics should be motivated. The degradation of hydrophobic pesticides including chlorpyrifos, dicofol and cypermethrin were assayed with the white-rot fungus Trametes versicolor. Experiments were set at realistic concentration as 5 μg L, and both culture medium and biologic matrix were analyzed for pollutants residues.

Dose-dependent improvement of cardiac function in a swine model of acute myocardial infarction after intracoronary administration of allogeneic heart-derived cells.

Background: Allogeneic cardiac-derived progenitor cells (CPC) without immunosuppression could provide an effective ancillary therapy to improve cardiac function in reperfused myocardial infarction. We set out to perform a comprehensive preclinical feasibility and safety evaluation of porcine CPC (pCPC) in the infarcted porcine model, analyzing biodistribution and mid-term efficacy, as well as safety in healthy non-infarcted swine.

Methods: The expression profile of several pCPC isolates was compared with humans using both FACS and RT-qPCR.

Definition of a cell surface signature for human cardiac progenitor cells after comprehensive comparative transcriptomic and proteomic characterization.

Adult cardiac progenitor/stem cells (CPC/CSC) are multipotent resident populations involved in cardiac homeostasis and heart repair. Assisted by complementary RNAseq analysis, we defined the fraction of the CPC proteome associable with specific functions by comparison with human bone marrow mesenchymal stem cells (MSC), the reference population for cell therapy, and human dermal fibroblasts (HDF), as a distant reference. Label-free proteomic analysis identified 526 proteins expressed differentially in CPC.

CXCL6 is an important paracrine factor in the pro-angiogenic human cardiac progenitor-like cell secretome.

Studies in recent years have established that the principal effects in cardiac cell therapy are associated with paracrine/autocrine factors. We combined several complementary techniques to define human cardiac progenitor cell (CPC) secretome constituted by 914 proteins/genes; 51% of these are associated with the exosomal compartment. To define the set of proteins specifically or highly differentially secreted by CPC, we compared human mesenchymal stem cells and dermal fibroblasts; the study defined a group of growth factors, cytokines and chemokines expressed at high to medium levels by CPC.

Comparison between several reactors with Trametes versicolor immobilized on lignocellulosic support for the continuous treatments of hospital wastewater.

Hospital wastewater is a major source of pharmaceutically active compounds (PhACs), which are not all removed in conventional wastewater treatment plants. White rot fungi can degrade PhACs, but their application has been limited to non-sterile conditions due to the competition with other microorganisms for growth. In this study, immobilization of Trametes versicolor on different lignocellulosic supports was studied as strategy to ensure fungal survival under continuous treatment conditions.

An Efficient Microarray-Based Genotyping Platform for the Identification of Drug-Resistance Mutations in Majority and Minority Subpopulations of HIV-1 Quasispecies.

The response of human immunodeficiency virus type 1 (HIV-1) quasispecies to antiretroviral therapy is influenced by the ensemble of mutants that composes the evolving population. Low-abundance subpopulations within HIV-1 quasispecies may determine the viral response to the administered drug combinations. However, routine sequencing assays available to clinical laboratories do not recognize HIV-1 minority variants representing less than 25% of the population.

Chemokine receptor homo- or heterodimerization activates distinct signaling pathways.

Chemokine receptors of both the CC and CXC families have been demonstrated to undergo a ligand-mediated homodimerization process required for Ca2+ flux and chemotaxis. We show that, in the chemokine response, heterodimerization is also permitted between given receptor pairs, specifically between CCR2 and CCR5. This has functional consequences, as the CCR2 and CCR5 ligands monocyte chemotactic protein-1 (MCP-1) and RANTES (regulated upon activation, normal T cell-expressed and secreted) cooperate to trigger calcium responses at concentrations 10- to 100-fold lower than the threshold for either chemokine alone.

Improvement in affinity and HIV-1 neutralization by somatic mutation in the heavy chain first complementarity-determining region of antibodies triggered by HIV-1 infection.

We assessed the impact of somatic hypermutation in the framework region 1 (FR1) and complementarity-determining region 1 (CDR1) of three clonally-related heavy chains from the human monovalent antigen-binding fragments Fab S19, S8 and S20 on gp120 binding and HIV-1 neutralization capacity. Nucleotide changes were introduced in the heavy chains to revert single and multiple amino acid residues, and two Fab libraries were constructed with the same light chain to express equivalent amounts of parental and reverted phage Fab. We studied the contribution of each amino acid replacement to antigen binding by calculating the frequency of phage Fab retrieval after competitive library selection on gp120.

Employment outcomes in family-aided assertive community treatment.

Family-aided assertive community treatment (FACT) was enhanced by adding vocational specialists to help persons with severe mental illness obtain competitive employment. Results were then tested against those of conventional vocational rehabilitation (CVR). The FACT cohort demonstrated significantly better employment rates than did the CVR, while negative symptoms declined in the former and increased in the latter.

Antibody repertoire against HIV-1 gp120 triggered in nude and normal mice by GM-CSF/gp120 immunization.

Granulocyte-macrophage colony stimulating factor (GM-CSF) facilitates the induction of primary immune responses by activating and recruiting antigen-presenting cells (APC), which efficiently present antigen determinants to Th cells. We have derived a functional GM-CSF/gp120 chimeric protein that, following immunization in soluble, adjuvant-independent form in normal mice, triggers highly specific, high affinity anti-gp120 antibodies. In contrast, nude mice respond with mutated, polyreactive, low affinity antibodies that mature further and increase in affinity in T cell-reconstituted nude mice.

Molecular analysis of HIV-1 gp120 antibody response using isotype IgM and IgG phage display libraries from a long-term non-progressor HIV-1-infected individual.

To characterize the variable heavy chain (VH)3 antibody response to HIV-1 gp120, we analyzed a panel of IgM and IgG1 Fab fragments from phage display isotype libraries from a long-term, non-progressor HIV-1-infected individual. The IgM Fab antibodies isolated had low affinity for gp120, were not restricted to a particular VH3 germ-line gene, and consisted mainly of unmutated VH genes. In contrast, IgG Fab fragments were gp120 specific, with high affinity and extensive somatic mutation; all were clonally related and were derived from a single VH3 germ-line gene (DP50).

Natural human antibodies retrieved by phage display libraries from healthy donors: polyreactivity and recognition of human immunodeficiency virus type 1gp120 epitopes.

We have characterized the human natural antibody repertoire that contains antibodies recognizing the human immunodeficiency virus type 1 (HIV-1) gp120. A panel of monovalent antigen-binding fragments (Fab) selected from IgM and IgG isotype libraries generated from peripheral blood mononuclear cells (PBMC) of a healthy, HIV-1 noninfected individual was analysed, reflecting that only IgM, but not IgG, Fab were able to recognize HIV-1 gp120. The IgM Fab antibodies were not restricted to any particular heavy chain variable region (VH) germ line gene.

Anti-Vbeta8 antibodies induce and maintain staphylococcal enterotoxin B-triggered Vbeta8+ T cell anergy.

The mechanism involved in the maintenance of staphylococcal enterotoxin B (SEB)-induced T cell anergy is poorly understood. We demonstrated earlier that B cells play an important role in the maintenance of SEB-induced T cell anergy in vivo and in vitro. Here, we demonstrate that B cells are not essential in SEB-induced T cell activation, but are important for the maintenance of T cell memory phenotype and anergy in vivo.

Suppression of HIV-1 infection in linomide-treated SCID-hu-PBL mice.

Background: Proinflammatory cytokine overproduction, as well as synthesis of the inducible form of nitric oxide synthase (iNOS), are known to play a major role in HIV-1-triggered disease. AIDS patients show increased serum tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma levels, which synergize with HIV-1-produced nitric oxide (NO) to augment viral replication. Linomide has strong immunomodulatory effects in animals and humans, yielding promising clinical benefits in several pathological disorders including septic shock and autoimmune disease, processes largely mediated by overproduction of these cytokines.

Identification and characterization of a new oncogene derived from the regulatory subunit of phosphoinositide 3-kinase.

p85/p110 phosphoinositide 3-kinase (PI3K) is a heterodimer composed of a p85-regulatory and a p110-catalytic subunit, which is involved in a variety of cellular responses including cytoskeletal organization, cell survival and proliferation. We describe here the cloning and characterization of p65-PI3K, a mutant of the regulatory subunit of PI3K, which includes the initial 571 residues of the wild type p85alpha-protein linked to a region conserved in the eph tyrosine kinase receptor family. We demonstrate that this mutation, obtained from a transformed cell, unlike previously engineered mutations of the regulatory subunit, induces the constitutive activation of PI3K and contributes to cellular transformation.

Multiple-family groups and psychoeducation in the treatment of schizophrenia.

Objective: To compare outcomes in psychoeducational multiple-family group treatment vs psychoeducational single-family treatment.

Method: A total of 172 acutely psychotic patients, aged 18 to 45 years, with DSM-III-R schizophrenic disorders were randomly assigned to single- or multiple-family psychoeducational treatment at six public hospitals in the state of New York. Psychotic relapse, symptom status, medication compliance, rehospitalization, and employment were assessed independently during 2 years of supervised treatment.