An investigation into the adjuvanticity and immunogenicity of zein microspheres being researched as drug and vaccine carriers.

We have determined whether zein microspheres could act as vaccine adjuvants i.e. increase the immune responses to co-administered immunogens. Ovalbumin (model antigen)-loaded zein microspheres, blank zein microspheres and ovalbumin solution were intramuscularly administered to mice and the sera antibody levels were determined by ELISA. Another group of mice was orally dosed with blank zein microspheres, and serum and faecal antibody levels were determined. As expected, negligible antibody titres were obtained with the ovalbumin solution. Surprisingly, intramuscular administrations of blank zein microspheres elicited high levels of serum IgG which bound to the ovalbumin antigen coated on ELISA microtitre plates. This indicated that anti-zein antibodies had been elicited by blank zein microspheres and that these antibodies were cross-reacting with ovalbumin antigen coated onto ELISA plates. Such cross-reactivity inhibited the determination of the adjuvant activity of zein microspheres, if any. Additional ELISA assays, where zein was used as the coating antigen, confirmed the generation of anti-zein antibodies by blank zein microspheres i.e. zein microspheres were immunogenic following intramuscular administration. Upon oral administration of blank zein microspheres, serum IgG levels remained low but intestinal IgA levels increased following booster doses i.e. systemic tolerance, but not mucosal tolerance, to oral zein particles was achieved. Zein microspheres were immunogenic when administered intramuscularly and orally

Kinetic and functional properties of human mitochondrial phosphoenolpyruvate carboxykinase

The cytosolic form of phosphoenolpyruvate carboxykinase (PCK1) plays a regulatory role in gluconeogenesis and glyceroneogenesis. The role of the mitochondrial isoform (PCK2) remains unclear. We report the partial purification and kinetic and functional characterization of human PCK2. Kinetic properties of the enzyme are very similar to those of the cytosolic enzyme. PCK2 has an absolute requirement for Mn2+ ions for activity; Mg2+ ions reduce the Km for Mn2+ by about 60 fold. Its specificity constant is 100 fold larger for oxaloacetate than for phosphoenolpyruvate suggesting that oxaloacetate phosphorylation is the favored reaction in vivo. The enzyme possesses weak pyruvate kinase-like activity (kcat=2.7 s-1). When overexpressed in HEK293T cells it enhances strongly glucose and lipid production showing that it can play, as the cytosolic isoenzyme, an active role in glyceroneogenesis and gluconeogenesis

Demagnetization via Nucleation of the Nonequilibrium Metastable Phase in a Model of Disorder

We study both analytically and numerically metastability and nucleation in a two-dimensional nonequilibrium Ising ferromagnet. Canonical equilibrium is dynamically impeded by a weak random perturbation which models homogeneous disorder of undetermined source. We present a simple theoretical description, in perfect agreement with Monte Carlo simulations, assuming that the decay of the nonequilibrium metastable state is due, as in equilibrium, to the competition between the surface and the bulk. This suggests one to accept a nonequilibrium "free-energy" at a mesoscopic/cluster level, and it ensues a nonequilibrium "surface tension" with some peculiar low-T behavior. We illustrate the occurrence of intriguing nonequilibrium phenomena, including: (i) Noise-enhanced stabilization of nonequilibrium metastable states; (ii) reentrance of the limit of metastability under strong nonequilibrium conditions; and (iii) resonant propagation of domain walls. The cooperative behavior of our system may also be understood in terms of a Langevin equation with additive and multiplicative noises. We also studied metastability in the case of open boundaries as it may correspond to a magnetic nanoparticle. We then observe burst-like relaxation at low T, triggered by the additional surface randomness, with scale-free avalanches which closely resemble the type of relaxation reported for many complex systems. We show that this results from the superposition of many demagnetization events, each with a well- defined scale which is determined by the curvature of the domain wall at which it originates. This is an example of (apparent) scale invariance in a nonequilibrium setting which is not to be associated with any familiar kind of criticality.Comment: 26 pages, 22 figure

The alhambra survey: evolution of galaxy spectral segregation

We study the clustering of galaxies as a function of spectral type and redshift in the range 0.35 <z <1.1 using data from the Advanced Large Homogeneous Area Medium Band Redshift Astronomical (ALHAMBRA) survey. The data cover 2.381 deg2 in 7 fields, after applying a detailed angular selection mask, with accurate photometric redshifts down to IAB <24. From this catalog we draw five fixed number density redshift-limited bins. We estimate the clustering evolution for two different spectral populations selected using the ALHAMBRA-based photometric templates: quiescent and star-forming galaxies. For each sample we measure the real-space clustering using the projected correlation function. Our calculations are performed over the range [0.03, 10.0] h-1 Mpc, allowing us to find a steeper trend for Mpc, which is especially clear for star-forming galaxies. Our analysis also shows a clear early differentiation in the clustering properties of both populations: star-forming galaxies show weaker clustering with evolution in the correlation length over the analyzed redshift range, while quiescent galaxies show stronger clustering already at high redshifts and no appreciable evolution. We also perform the bias calculation where similar segregation is found, but now it is among the quiescent galaxies where a growing evolution with redshift is clearer (abrigatted). These findings clearly corroborate the well-known color-density relation, confirming that quiescent galaxies are mainly located in dark matter halos that are more massive than those typically populated by star-forming galaxies.Ministerio de Economía y Competitividad y FEDER AYA2010-22111-C03-02 AYA2013-48623-C2-2 AYA2012-39620 AYA2013-40611-P AYA2013-42227-P AYA2013-43188-P AYA2013-48623-C2-1 ESP2013-48274 AYA2014-58861-C3-1Junta de Andalucía TIC114 JA2828 P10-FQM-644

Controlled release from zein matrices: Interplay of drug hydrophobicity and pH

Purpose: In earlier studies, the corn protein zein is found to be suitable as a sustained release agent, yet the range of drugs for which zein has been studied remains small. Here, zein is used as a sole excipient for drugs differing in hydrophobicity and isoelectric point: indomethacin, paracetamol and ranitidine. Methods: Caplets were prepared by hot-melt extrusion (HME) and injection moulding (IM). Each of the three model drugs were tested on two drug loadings in various dissolution media. The physical state of the drug, microstructure and hydration behaviour were investigated to build up understanding for the release behaviour from zein based matrix for drug delivery. Results: Drug crystallinity of the caplets increases with drug hydrophobicity. For ranitidine and indomethacin, swelling rates, swelling capacity and release rates were pH dependent as a consequence of the presence of charged groups on the drug molecules. Both hydration rates and release rates could be approached by existing models. Conclusion: Both the drug state as pH dependant electrostatic interactions are hypothesised to influence release kinetics. Both factors can potentially be used factors influencing release kinetics release, thereby broadening the horizon for zein as a tuneable release agent

Compilation of a social network lexicon for determining the profile of authors

The use of social networks is steadily increasing worldwide. Hundreds of users daily register in the different existing platforms, therefore, the content extracted from the social networks is fundamental for tasks such as sentiment analysis, detection of author profiles, identification of authors, opinions mining, plagiarism detection, calculation of similarity between texts and to develop robust systems that help to make decisions in related areas such as politics, education, economy, among others. This paper provides a lexical aid for the pre-processing of texts posted in social networks evolved for the subsequent languages: English, Spanish, Dutch and Italian

Levantamiento por Compresión del piso del Seno del Maxilar. Técnica Transcrestal con Osteótomo. Descripción de un caso clínico.

Las limitaciones anatómicas causadas por la pérdida dental como la neumatizacion de seno maxilar y la poca altura del hueso alveolar en relacion con el seno del maxilar impide la colocacion del implante oseointegrado. No obstante el piso del seno del maxilar posee caracteristicas estructurales que permiten la compresion  ósea  y posicionan al implante con estabilidad primaria ideal. El objetivo de este artículo es describir un caso clínico donde se relata la preparacion, levantamiento y compresión del piso del seno del maxilar por intermedio de la Técnica Transcrestal y el uso de osteótomos con la finalidad de ganar altura y estabilidad primaria con la bicorticalización

The ALHAMBRA survey: evolution of galaxy spectral segregation

We study the clustering of galaxies as a function of spectral type and redshift in the range $0.35 < z < 1.1$ using data from the Advanced Large Homogeneous Area Medium Band Redshift Astronomical (ALHAMBRA) survey. The data cover 2.381 deg$^2$ in 7 fields, after applying a detailed angular selection mask, with accurate photometric redshifts [$\sigma_z < 0.014(1+z)$] down to $I_{AB} < 24$. From this catalog we draw five fixed number density, redshift-limited bins. We estimate the clustering evolution for two different spectral populations selected using the ALHAMBRA-based photometric templates: quiescent and star-forming galaxies. For each sample, we measure the real-space clustering using the projected correlation function. Our calculations are performed over the range $[0.03,10.0] h^{-1}$ Mpc, allowing us to find a steeper trend for $r_p \lesssim 0.2 h^{-1}$ Mpc, which is especially clear for star-forming galaxies. Our analysis also shows a clear early differentiation in the clustering properties of both populations: star-forming galaxies show weaker clustering with evolution in the correlation length over the analysed redshift range, while quiescent galaxies show stronger clustering already at high redshifts, and no appreciable evolution. We also perform the bias calculation where similar segregation is found, but now it is among the quiescent galaxies where a growing evolution with redshift is clearer. These findings clearly corroborate the well known colour-density relation, confirming that quiescent galaxies are mainly located in dark matter halos that are more massive than those typically populated by star-forming galaxies.Comment: 14 pages, 9 figures, accepted by Ap

The role of clonal communication and heterogeneity in breast cancer

Background: Cancer is a rapidly evolving, multifactorial disease that accumulates numerous genetic and epigenetic alterations. This results in molecular and phenotypic heterogeneity within the tumor, the complexity of which is further amplified through specific interactions between cancer cells. We aimed to dissect the molecular mechanisms underlying the cooperation between different clones. Methods: We produced clonal cell lines derived from the MDA-MB-231 breast cancer cell line, using the UbC-StarTrack system, which allowed tracking of multiple clones by color: GFP C3, mKO E10 and Sapphire D7. Characterization of these clones was performed by growth rate, cell metabolic activity, wound healing, invasion assays and genetic and epigenetic arrays. Tumorigenicity was tested by orthotopic and intravenous injections. Clonal cooperation was evaluated by medium complementation, co-culture and co-injection assays. Results: Characterization of these clones in vitro revealed clear genetic and epigenetic differences that affected growth rate, cell metabolic activity, morphology and cytokine expression among cell lines. In vivo, all clonal cell lines were able to form tumors; however, injection of an equal mix of the different clones led to tumors with very few mKO E10 cells. Additionally, the mKO E10 clonal cell line showed a significant inability to form lung metastases. These results confirm that even in stable cell lines heterogeneity is present. In vitro, the complementation of growth medium with medium or exosomes from parental or clonal cell lines increased the growth rate of the other clones. Complementation assays, co-growth and co-injection of mKO E10 and GFP C3 clonal cell lines increased the efficiency of invasion and migration. Conclusions: These findings support a model where interplay between clones confers aggressiveness, and which may allow identification of the factors involved in cellular communication that could play a role in clonal cooperation and thus represent new targets for preventing tumor progression