Cellular xenotransplantation of animal cells into people: benefits and risk

The main benefit of xenotransplantation is its potential to overcome the worldwide organ shortage experienced in allotransplantation. Allogeneic transplantation is the only successful therapy for several life-threatening diseases, with cell, tissue or organ donation only partially meeting the demand and many patients dying while waiting for treatment. With supply falling short of demand, it is foreseen that the use of porcine material may at some stage overcome the existing gap between organ availability and clinical need. Recently, pig islet cells have been utilised in clinical trials, with safety being demonstrated. Indeed, pig-derived cells present several advantages: i) porcine cells have a stable function and differentiation pattern and are not tumorigenic; ii) pig cells have been shown to meet the physiological needs in large animal models; iii) the source of pig cells can be scaled up to meet demands in a highly standardised manner, and with respect to animal welfare regulations; iv) ‘designated-pathogen-free’ (DPF) pig lines can be produced, which could result in a higher safety profile than allotransplantation itself; v) the risk of zoonosis, which was raised years ago as the major hurdle, has been recently circumvented and is actually viewed as a controlled risk; and vi) immune risks are being circumvented via the use of genetically modified donor animals and encapsulation of porcine cells, particularly for the treatment of diabetes. Overall, the benefit appears to outweigh potential risks with respect to cellular xenotransplantation and this is discussed further in this review

Stereospecific synthesis of syn-alpha-oximinoamides by a three-component reaction of isocyanides, syn-chlorooximes, and carboxylic acids

A stereospecific multicomponent reaction among isocyanides, nitrile N-oxides and carboxylic acids provides an efficient synthesis of biologically relevant syn \u3b1-oximinoimides

High-resolution genetic map of the Rvi15 ( Vr2 ) apple scab resistance locus

The Rvi15 (Vr2) apple scab resistance locus found in the GMAL 2473 accession has been previously mapped to the top of the Linkage Group 2 (LG2) by analyzing 89 progeny plants of a cross between ‘Idared' and GMAL 2473. A new population of 989 progeny plants, derived from a cross between ‘Golden Delicious' and GMAL 2473, has been analyzed with the two SSR markers CH02c02a and CH02f06, previously found to be associated with Rvi15 (Vr2), and with two published markers derived from NBS sequences (ARGH17 and ARGH37) estimated to map close to the Rvi15 (Vr2) locus. ARGH17 and ARGH37, were found to be the closest markers to the resistance locus, bracketing it within an interval of 1.5cM. The SSRs mapped one on each side of Rvi15 (Vr2). CH02f06 mapped at 2.9cM from ARGH37 while CH02a02a mapped at 1.7 from ARGH17. The position of Rvi15 (Vr2) respect to CH02a02a indicates that Rvi15 (Vr2) and Rvi4 (Vh4), a second apple scab gene mapped on the top of LG2, are two different resistance genes. In order to develop even more tightly linked markers to Rvi15 (Vr2), ARGH17 was used as the starting point for chromosome walking through the Rvi15 (Vr2) homolog region of the cv. ‘Florina'. A single ‘Florina' BAC clone, 36I17, was sufficient to span the homologous locus in the new population's recombinant progeny. Sequencing of the 36I17 BAC clone allowed identifying seven putative ORFs, including two showing a TIR-NBS-LRR structure. Ten additional markers could be developed mapping within a 1.8cM interval around the Rvi15 (Vr2) resistance gene. ARGH17 and GmTNL1 markers, the latter also derived from NBS-LRR resistance gene homolog sequence, are the closest markers to Rvi15 (Vr2) bracketing it within a 0.5cM interval. The availability of 12 markers within the Rvi15 (Vr2) region, all within a small physical distance (kbp) in ‘Florina', suggests that cloning of the Rvi15 (Vr2) apple scab resistance gene from GMAL 2473 will be possibl

Assessment of telomere length during post-natal period in offspring produced by a bull and its fibroblast derived clone

Objective: To investigate the telomere length in bovine offspring produced by a cloned and control bull, and the telomerase activity in embryos produced with the same technology. Methods: Five daughters of a control and five daughters of a bull cloned using a fibroblast of the control were produced by IVF using sperm of the two bulls. Blood samples of the offspring were collected at 2, 6, and 12 months of age and the relative telomere length (RTL) was assessed by flow cytometry. At same time the body growth, hematological profile, and clinical biochemistry of the same progeny was extensively surveyed, and results have been reported in a previous work. Thereafter, the telomerase activity was assessed using a real time PCR quantitative assay in groups of embryos produced with the same technology. Results: The offspring of the clone exhibited a modest, but significant (P<0.05), shortening of the telomeres (21.36%, 20.56% and 20.56%) compared to that of the control (23.78%, 23.53% and 22.43%) as mean values determined at 2, 6 and 12 months, respectively. Shortening of telomeres in respect to the age was not significant. No statistical difference was reported between telomerase activity assessed in 144 cloned (3.4−03 ± 2.4−03 amoles/μL) and 80 control (2.1−03 ± 1.8−03 amoles/μL) embryos. Conclusions: The results have revealed a moderate shortening of telomeres in the offspring of the clone with respect to control. However, this study did not evidence differences in the two progenies that suggest welfare problems during the first year of life

Design of hearing aid shells by three dimensional laser scanning and mesh reconstruction

Hearing aid shells (or earmolds) must couple the hearing aid with the user's ear. Earmolds have to fit the subject's outer ear canal properly to ensure a good performance of the aid. Because of the great variability in the anatomical pattern of the ear, earmolds are custom made. At present, an impression of the subject's ear canal is taken and used to fabricate the silicon-made mold. The postimpression activities that typically are performed during the fabrication process modify the physical dimensions of the resulting earmold and thus affect the fit of the product. A novel system for 3-D laser scanning and mesh reconstruction of the surface of ear canal impressions is presented. The reconstructed impression can be digitally stored and passed directly to dedicated CAD 3-D printing machines to model the silicon earmold and thus achieve the best possible fit. The proposed system is based on a couple of cameras and a commercial laser for the surface digitization and on a straightforward algorithm, based on the deformation of a geometric model, for the reconstruction of the acquired surface. Measurements on objects of well-known geometric features and dimensions are performed to assess the accuracy and repeatability levels of this 3-D acquisition system. Robustness to noise of the proposed reconstruction algorithm is determined by simulations with a synthetic test surface. Finally, the first measurements (acquisition+reconstruction) of closed surfaces from ear canal impressions are reported

Vacuoles Induced by Helicobacter pylori Toxin Contain Both Late Endosomal and Lysosomal Markers

Intoxication of mammalian cells with the vacuolating toxin (VacA) released by Helicobacter pylori causes the formation of large acidic vacuoles containing the vacuolar ATPase proton pump and Rab7, a late endosome marker. Here, we describe a novel subcellular fractionation procedure, and we show that nanomolar concentrations of VacA induce a clear redistribution of lysosomal membrane glycoproteins among endocytic compartments. This redistribution is an early event in the process of cellular intoxication by VacA and precedes the formation of macroscopic vacuoles. The absence of the cation independent mannose 6-P receptor and the presence of Rab7 and of lysosomal membrane proteins in the newly formed compartment suggest that the vacuolating toxin induces the accumulation of a post-endosomal hybrid compartment presenting both late endosomal and lysosomal features

Differential Immune Response to Bioprosthetic Heart Valve Tissues in the α1,3Galactosyltransferase-Knockout Mouse Model

Anti-Gal antibodies; Bioprosthetic heart valves; Cellular immune infiltrateAnticuerpos anti-Gal; Válvulas cardíacas bioprotésicas; Infiltrado inmune celularAnticossos anti-Gal; Vàlvules cardíaques bioprotèsiques; Infiltrat immune cel·lularStructural valve deterioration (SVD) of bioprosthetic heart valves (BHVs) has great clinical and economic consequences. Notably, immunity against BHVs plays a major role in SVD, especially when implanted in young and middle-aged patients. However, the complex pathogenesis of SVD remains to be fully characterized, and analyses of commercial BHVs in standardized-preclinical settings are needed for further advancement. Here, we studied the immune response to commercial BHV tissue of bovine, porcine, and equine origin after subcutaneous implantation into adult α1,3-galactosyltransferase-knockout (Gal KO) mice. The levels of serum anti-galactose α1,3-galactose (Gal) and -non-Gal IgM and IgG antibodies were determined up to 2 months post-implantation. Based on histological analyses, all BHV tissues studied triggered distinct infiltrating cellular immune responses that related to tissue degeneration. Increased anti-Gal antibody levels were found in serum after ATS 3f and Freedom/Solo implantation but not for Crown or Hancock II grafts. Overall, there were no correlations between cellular-immunity scores and post-implantation antibodies, suggesting these are independent factors differentially affecting the outcome of distinct commercial BHVs. These findings provide further insights into the understanding of SVD immunopathogenesis and highlight the need to evaluate immune responses as a confounding factor.This research was funded by the European Union Seventh Framework Programme (FP7/2007–2013) under Grant Agreement no. 603049, TRANSLINK. This work was also supported by Ministerio de Economía y Competitividad-ISCiii (PI15/00181) and the PERIS SLT002/16/00445 funded by the Department of Health of Generalitat de Catalunya, all granted to CC and co-funded by FEDER funds, a way to build Europe. IDIBELL benefits from CERCA support. S.G.K. was partially supported by an IDIBELL summer internship. The funding agencies did not influence in any other way than by providing financial support

Application of decision tools to ethical analysis in biodiversity conservation

Achieving ethically responsible decisions is crucial for the success of biodiversity conservation projects. We adapted the ethical matrix, decision tree, and Bateson's cube to assist in the ethical analysis of complex conservation scenarios by structuring these tools so that they can implement the different value dimensions (environmental, social, and animal welfare) involved in conservation ethics. We then applied them to a case study relative to the decision-making process regarding whether or not to continue collecting biomaterial on the oldest of the two remaining northern white rhinoceroses (Ceratotherium simum cottoni), a functionally extinct subspecies of the white rhinoceros. We used the ethical matrix to gather ethical pros and cons and as a starting point for a participatory approach to ethical decision-making. We used decision trees to compare the different options at stake on the basis of a set of ethical desiderata. We used Bateson's cube to establish a threshold of ethical acceptability and model the results of a simple survey. The application of these tools proved to be pivotal in structuring the decision-making process and in helping reach a shared, reasoned, and transparent decision on the best option from an ethical point of view among those available