The iFat1 transgene permits conditional endogenous n-3 PUFA enrichment both in vitro and in vivo

Fat-1 transgenic mice, which endogenously convert n-6 PUFA to n-3 PUFA, are a useful tool in health research; however with this model timing of n-3 PUFA enrichment cannot be directly controlled. To add such capability, the novel Cre-recombinase inducible fat-1 (iFat1) transgenic mouse has been developed. The aim of this study was to characterize the utility of the iFat1 transgene as a model of Cre-inducible endogenous n-3 PUFA enrichment. Functionality of the iFat1 transgene was screened both in vitro and in vivo. In the presence of Cre, the iFat1 transgene resulted in a balancing (p < 0.01) of the n-6/n-3 PUFA ratio within phospholipids in the human embryonic kidney 293T cell line. For in vivo analysis, iFat1 transgenic mice were crossed with the R26-Cre-ERT2 (Tam-Cre) mouse line, a tamoxifen inducible Cre-expression model. Tam-Cre/iFat1 double hybrids were transiently treated with tamoxifen at 6–7 weeks, then terminated 3 weeks later. Tamoxifen treated mice had increased (p < 0.05) tissue n-3 PUFA and ≥two-fold reduction (p < 0.05) in the n-6/n-3 PUFA ratio of liver, kidney and muscle phospholipids relative to vehicle treated controls. Collectively these findings suggest that the iFat1 transgenic mouse may be a promising tool to help elucidate the temporal effects through which n-3 PUFA impacts health related outcomes

Single-Molecule Unbinding Forces between the Polysaccharide Hyaluronan and Its Binding Proteins

The extracellular polysaccharide hyaluronan (HA) is ubiquitous in all vertebrate tissues, where its various functions are encoded in the supramolecular complexes and matrices that it forms with HA-binding proteins (hyaladherins). In tissues, these supramolecular architectures are frequently subjected to mechanical stress, yet how this affects the intermolecular bonding is largely unknown. Here, we used a recently developed single-molecule force spectroscopy platform to analyze and compare the mechanical strength of bonds between HA and a panel of hyaladherins from the Link module superfamily, namely the complex of the proteoglycan aggrecan and cartilage link protein, the proteoglycan versican, the inflammation-associated protein TSG-6, the HA receptor for endocytosis (stabilin-2/HARE), and the HA receptor CD44. We find that the resistance to tensile stress for these hyaladherins correlates with the size of the HA-binding domain. The lowest mean rupture forces are observed for members of the type A subgroup (i.e., with the shortest HA-binding domains; TSG-6 and HARE). In contrast, the mechanical stability of the bond formed by aggrecan in complex with cartilage link protein (two members of the type C subgroup, i.e., with the longest HA-binding domains) and HA is equal or even superior to the high affinity streptavidin,biotin bond. Implications for the molecular mechanism of unbinding of HA, hyaladherin bonds under force are discussed, which underpin the mechanical properties of HA, hyaladherin complexes and HA-rich extracellular matrices

Generation of cloned transgenic pigs rich in omega-3 fatty acids

Meat products are generally low in omega-3 (n-3) fatty acids, which are beneficial to human health. We describe the generation of cloned pigs that express a humanized Caenorhabditis elegans gene, fat-1, encoding an n-3 fatty acid desaturase. The hfat-1 transgenic pigs produce high levels of n-3 fatty acids from n-6 analogs, and their tissues have a significantly reduced ratio of n-6/n-3 fatty acids (P < 0.001). © 2006 Nature Publishing Group

Time-resolved detection and analysis of single nanoparticle electrocatalytic impacts

There is considerable interest in understanding the interaction and activity of single entities, such as (electro)catalytic nanoparticles (NPs), with (electrode) surfaces. Through the use of a high bandwidth, high signal/noise measurement system, NP impacts on an electrode surface are detected and analyzed in unprecedented detail, revealing considerable new mechanistic information on the process. Taking the electrocatalytic oxidation of H2O2 at ruthenium oxide (RuOx) NPs as an example, the rise time of current–time transients for NP impacts is consistent with a hydrodynamic trapping model for the arrival of a NP with a distance-dependent NP diffusion-coefficient. NP release from the electrode appears to be aided by propulsion from the electrocatalytic reaction at the NP. High-frequency NP impacts, orders of magnitude larger than can be accounted for by a single pass diffusive flux of NPs, are observed that indicate the repetitive trapping and release of an individual NP that has not been previously recognized. The experiments and models described could readily be applied to other systems and serve as a powerful platform for detailed analysis of NP impacts

Estudio de la rugosidad superficial de implantes dentales de titanio blastinizados mediante microscopía electrónica de barrido en 3D

Una de las actividades más importantes en el estudio de los implantes dentales de Ti c.p. se encuentra enfocada al uso de modificaciones superficiales mediante métodos físicos o químicos, debido a que ensayos in vivo han puesto de manifiesto que ciertas superficies rugosas producen una mejor fijación por osteoaposición de hueso que la correspondiente a superficies lisas, por lo que resulta necesario realizar una adecuada caracterización de la rugosidad de los mismos. Una gran variedad de tratamientos superficiales son utilizados para incrementar la rugosidad de los implantes dentales de Ti c.p.. De todos ellos, el más utilizado es el blastinizado. En éste, las partículas abrasivas son arrastradas por una corriente de aire hasta impactar con el material siendo algunas de las diferentes variables operativas del proceso el tamaño de partícula y la presión. Existe una gran variedad de parámetros que describen la topografía de las superficies entre los cuales se encuentran los grupos de parámetros de amplitud, híbridos y funcionales. La correcta elección de los parámetros más significativos dependerá de las características del tratamiento superficial utilizado y del objetivo del estudio realizado. En el presente trabajo se realiza una caracterización, por microscopía electrónica de barrido 3D, de la superficie de muestras de Ti c.p. sometidas a diferentes condiciones de blastinizado, proporcionadas por una empresa fabricante de implantes dentalesFil: Kang, Kyung W.. Universidad Nacional de La Plata. Facultad de ingenieria. Laboratorio de Investigaciones de Metalurgia Física; ArgentinaFil: Pereda, Maria D.. Universidad Nacional de La Plata. Facultad de ingenieria. Laboratorio de Investigaciones de Metalurgia Física; ArgentinaFil: Lemos, Adriana. Universidad Nacional de La Plata. Facultad de ingenieria. Laboratorio de Investigaciones de Metalurgia Física; ArgentinaFil: Bilmes, Pablo David. Universidad Nacional de La Plata. Facultad de ingenieria. Laboratorio de Investigaciones de Metalurgia Física; ArgentinaFil: Bonetto, Rita Dominga. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas; ArgentinaFil: Scarano, Mariano. Kinetical SRL Insumos Medicos; Argentin

Genomics-based re-examination of the taxonomy and phylogeny of human and simian Mastadenoviruses: an evolving whole genomes approach, revealing putative zoonosis, anthroponosis, and amphizoonosis

With the advent of high-resolution and cost-effective genomics and bioinformatics tools and methods contributing to a large database of both human (HAdV) and simian (SAdV) adenoviruses, a genomics-based re-evaluation of their taxonomy is warranted. Interest in these particular adenoviruses is growing in part due to the applications of both in gene transfer protocols, including gene therapy and vaccines, as well in oncolytic protocols. In particular, the re-evaluation of SAdVs as appropriate vectors in humans is important as zoonosis precludes the assumption that human immune system may be na€ıve to these vectors. Additionally, as impor- tant pathogens, adenoviruses are a model organism system for understanding viral pathogen emergence through zoonosis and anthroponosis, particularly among the primate species, along with recombination, host adaptation, and selection, as evidenced by one long-standing human respiratory pathogen HAdV-4 and a recent re-evaluation of another, HAdV-76. The latter reflects the insights on amphizoonosis, defined as infections in both directions among host species including “other than human”, that are pos- sible with the growing database of nonhuman adenovirus genomes. HAdV-76 is a recombinant that has been isolated from human, chimpanzee, and bonobo hosts. On-going and potential impacts of adenoviruses on public health and translational medicine drive this evaluation of 174 whole genome sequences from HAdVs and SAdVs archived in GenBank. The conclusion is that rather than separate HAdV and SAdV phylogenetic lineages, a single, intertwined tree is observed with all HAdVs and SAdVs forming mixed clades. Therefore, a single designation of “primate adenovirus” (PrAdV) superseding either HAdV and SAdV is proposed, or alter- natively, keeping HAdV for human adenovirus but expanding the SAdV nomenclature officially to include host species identifica- tion as in ChAdV for chimpanzee adenovirus, GoAdV for gorilla adenovirus, BoAdV for bonobo adenovirus, and ad libitum

The use of patient-reported outcome measures to guide referral for hip and knee replacement. Part 1: the development of an evidence based model linking pre-operative score to the probability of gaining benefit from surgery

Aims To calculate how the likelihood of obtaining measurable benefit from hip or knee arthroplasty varies with preoperative patient-reported scores. Methods Existing UK data from 222,933 knee and 209,760 hip arthroplasty patients were used to model an individual’s probability of gaining meaningful improvement after surgery based on their preoperative Oxford Knee or Hip Score (OKS/OHS). A clinically meaningful improvement after arthroplasty was defined as ≥ 8 point improvement in OHS, and ≥ 7 in OKS. Results The upper preoperative score threshold, above which patients are unlikely to achieve any meaningful improvement from surgery, is 41 for knees and 40 for hips. At lower scores, the probability of improvement increased towards a maximum of 88% (knee) and 95% for (hips). Conclusion By our definition of meaningful improvement, patients with preoperative scores above 41 (OKS) and 40 (OHS) should not be routinely referred to secondary care for possible arthroplasty. Using lower thresholds would incrementally increase the probability of meaningful benefit for those referred but will exclude some patients with potential to benefit. The findings are useful to support the complex shared decision-making process in primary care for referral to secondary care; and in secondary care for experienced clinicians counselling patients considering knee or hip arthroplasty, but should not be used in isolation