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

Facilitating development of research ethics and integrity leadership competencies

To build a culture of integrity in a HE institution, innovative approaches are needed to enhance education of research ethics and integrity (REI). In addition to educating students, understanding is needed on how to facilitate for those who lead others. The focus is on early-career researchers (ECRs) as future REI leaders. The current study sheds light on how learning and REI leadership competencies evolve during scaffolded collaborative research ethics training for this target group. The study combines new instruments as part of holistic DBR. Data was collected from 3 groups of experienced researchers attending 3 training sessions in the form of written group reports and group discussion recordings. Qualitative deductive analysis was utilised for monitoring the learning process, scaffolding patterns, and display of REI leadership principles. Also, quantitative analysis was applied to group discussion data, displaying the nature of collaboration. Results imply that collaborative case-based role play format is effective in training future REI leaders. All groups displayed high levels of understanding. Combining ECRs and researchers with leadership experience supported knowledge building in the groups by bringing in various perspectives. Even though groups required different amounts of scaffolding, the nature was similar: maintaining goal orientation, highlighting critical features and redirecting learners. Learning analytics of collaboration indicated that the person with leadership experience was not necessarily the most active participant nor took the role of a 'group leader'. Still, it was mostly that person who displayed leadership competencies thus supporting other group members to develop leadership aspects.Peer reviewe

Group-theoretical approach to a non-central extension of the Kepler-Coulomb problem

Bound and scattering states of a non-central extension of the three-dimensional Kepler-Coulomb Hamiltonian are worked out analytically within the framework of the potential groups of the problem, SO(7) for bound states and SO(6,1) for scattering states. In the latter case, the S matrix is calculated by the method of intertwining operators.Comment: 12 pages, to appear in J. Phys. A : Math. Theo

The Marketing and Reception of Women Writers in the Twenty-First Century Spanish Nation-State

The Marketing and Reception of Women Writers in the Twenty-First Century Spanish Nation-State By Jennifer Anne Rodriguez This thesis is a comparative study of the marketing and reception of women writers in the twenty-first century Spanish nation-state; more specifically, Galicia, Catalonia, the Basque Country and central Spain. This study analyses and discusses the strategies women writers in the Spanish nation-state use to achieve success and visibility within their respective literary fields, and also takes into account the complex situation that surrounds these women writers. As such, this thesis also discusses issues including language choice and national identity, as well as how women writers negotiate their position with their respective literary fields. Taking a cultural studies approach, this thesis takes eight women writers as case studies: María Xosé Queizán and María Reimóndez (Galicia); Mariasun Landa and Laura Mintegi (the Basque Country); Carme Riera and Maria de la Pau Janer (Catalonia); and Almudena Grandes and Lucía Etxebarria (central Spain) and examines the individual strategies they use to market their work and achieve success, associating themselves with canonical authors and careful use of paratexts such as prologues and epilogues. In addition, the reception of their mediated identities and their work is discussed through analysis of reviews and interviews in the press. This thesis shows that that women writers in the Spanish nation-state are engaged constantly in a complex negotiation of various inter-dependent factors. Achieving success – both economic and symbolic – is a complex process, and there may often be cases where economic success can be detrimental to symbolic success, or vice versa. However, if women writers in the Spanish nation-state are able to negotiate these complex inter-dependent factors, success – both economic and symbolic -, prestige and even canonisation are achievable

Nephroprotective Effect of the Virgin Olive Oil Polyphenol Hydroxytyrosol in Type 1-like Experimental Diabetes Mellitus: Relationships with Its Antioxidant Effect

The aim of this study was to determine whether hydroxytyrosol administration prevented kidney damage in an experimental model of type 1 diabetes mellitus in rats. Hydroxytyrosol was administered to streptozotocin-diabetic rats: 1 and 5 mg/kg/day p.o. for two months. After hydroxytyrosol administration, proteinuria was significantly reduced (67–73%), calculated creatinine clearance was significantly increased (26–38%), and the glomerular volume and glomerulosclerosis index were decreased (20–30%). Hydroxytyrosol reduced oxidative and nitrosative stress variables and thromboxane metabolite production. Statistical correlations were found between biochemical and kidney function variables. Oral administration of 1 and 5 mg/kg/day of hydroxytyrosol produced an antioxidant and nephroprotective effect in an experimental model of type 1-like diabetes mellitus. The nephroprotective effect was significantly associated with the systemic and renal antioxidant action of hydroxytyrosol, which also influenced eicosanoid production

The Fasciola hepatica thioredoxin: High resolution structure reveals two oxidation states.

addresses: Henry Wellcome Building for Biocatalysis, School of Biosciences, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.types: Comparative Study; Journal Article; Research Support, Non-U.S. Gov'tCopyright © 2008 Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Molecular and Biochemical Parasitology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Molecular and Biochemical Parasitology, 2008, Vol. 161, Issue 1, pp. 44 – 48 DOI: 10.1016/j.molbiopara.2008.06.009The Fasciola hepatica thioredoxin protein structure has been determined to 1.45A resolution. This is the first example of a single crystal structure to show the active site cysteine residues in both the reduced and disulfide oxidised form. Consistent with this observation the process of oxidation appears to require very little rearrangement of the surrounding protein structure. The F. hepatica thioredoxin structure has been compared to other thioredoxin protein structures already known and is found to be highly conserved. The F. hepatica protein is most similar to that of the thioredoxin from its human and animal hosts but it resembles other parasitic thioredoxins with regard to having no additional cysteine residues and is therefore not regulated by transient disulfide bond formation as proposed for thioredoxins from higher eukaryotic species

Intracellular trafficking and cellular uptake mechanism of PHBV nanoparticles for targeted delivery in epithelial cell lines

Indexación: Web of Science; Scopus; Scielo.Background: Nanotechnology is a science that involves imaging, measurement, modeling and a manipulation of matter at the nanometric scale. One application of this technology is drug delivery systems based on nanoparticles obtained from natural or synthetic sources. An example of these systems is synthetized from poly(3-hydroxybutyrate-co-3-hydroxyvalerate), which is a biodegradable, biocompatible and a low production cost polymer. The aim of this work was to investigate the uptake mechanism of PHBV nanoparticles in two different epithelial cell lines (HeLa and SKOV-3). Results: As a first step, we characterized size, shape and surface charge of nanoparticles using dynamic light scattering and transmission electron microscopy. Intracellular incorporation was evaluated through flow cytometry and fluorescence microscopy using intracellular markers. We concluded that cellular uptake mechanism is carried out in a time, concentration and energy dependent way. Our results showed that nanoparticle uptake displays a cell-specific pattern, since we have observed different colocalization in two different cell lines. In HeLa (Cervical cancer cells) this process may occur via classical endocytosis pathway and some internalization via caveolin-dependent was also observed, whereas in SKOV-3 (Ovarian cancer cells) these patterns were not observed. Rearrangement of actin filaments showed differential nanoparticle internalization patterns for HeLa and SKOV-3. Additionally, final fate of nanoparticles was also determined, showing that in both cell lines, nanoparticles ended up in lysosomes but at different times, where they are finally degraded, thereby releasing their contents. Conclusions: Our results, provide novel insight about PHBV nanoparticles internalization suggesting that for develop a proper drug delivery system is critical understand the uptake mechanism.https://jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-016-0241-

Quantum fluctuations in high field magnetization of 2D square lattice J1-J2 antiferromagnets

The J1-J2 square lattice Heisenberg model with spin S=1/2 has three phases with long-range magnetic order and two unconventionally ordered phases depending on the ratio of exchange constants. It describes a number of recently found layered vanadium oxide compounds. A simple means of investigating the ground state is the study of the magnetization curve and high-field susceptibility. We discuss these quantities by using the spin-wave theory and the exact diagonalization in the whole J1-J2 plane. We compare both results and find good overall agreement in the sectors of the phase diagram with magnetic order. Close to the disordered regions the magnetization curve shows strong deviations from the classical linear behaviour caused by large quantum fluctuations and spin-wave approximation breaks down. On the FM side (J1<0) where one approaches the quantum gapless spin nematic ground state this region is surprisingly large. We find that inclusion of second order spin-wave corrections does not lead to fundamental improvement. Quantum corrections to the tilting angle of the ordered moments are also calculated. They may have both signs, contrary to the always negative first order quantum corrections to the magnetization. Finally we investigate the effect of the interlayer coupling and find that the quasi-2D picture remains valid up to |J_\perp/J1| ~ 0.3.Comment: 13 pages, 6figure