Hypoxic pre-conditioning increases the infiltration of endothelial cells into scaffolds for dermal regeneration pre-seeded with mesenchymal stem cells.

Many therapies using mesenchymal stem cells (MSC) rely on their ability to produce and release paracrine signals with chemotactic and pro-angiogenic activity. These characteristics, however, are mostly studied under standard in vitro culture conditions. In contrast, various novel cell-based therapies imply pre-seeding MSC into bio-artificial scaffolds. Here we describe human bone marrow-derived MSC seeded in Integra matrices, a common type of scaffold for dermal regeneration (SDR). We show and measured the distribution of MSC within the SDR, where cells clearly establish physical interactions with the scaffold, exhibiting constant metabolic activity for at least 15 days. In the SDR, MSC secrete VEGF and SDF-1α and induce transwell migration of CD34(+) hematopoietic/endothelial progenitor cells, which is inhibited in the presence of a CXCR4/SDF-1α antagonist. MSC in SDR respond to hypoxia by altering levels of angiogenic signals such as Angiogenin, Serpin-1, uPA, and IL-8. Finally, we show that MSC-containing SDR that have been pre-incubated in hypoxia show higher infiltration of endothelial cells after implantation into immune deficient mice. Our data show that MSC are fully functional ex vivo when implanted into SDR. In addition, our results strongly support the notion of hypoxic pre-conditioning MSC-containing SDR, in order to promote angiogenesis in the wounds

Lifetimes of Confined Acoustic Phonons in Ultra-Thin Silicon Membranes

We study the relaxation of coherent acoustic phonon modes with frequencies up to 500 GHz in ultra-thin free-standing silicon membranes. Using an ultrafast pump-probe technique of asynchronous optical sampling, we observe that the decay time of the first-order dilatational mode decreases significantly from \sim 4.7 ns to 5 ps with decreasing membrane thickness from \sim 194 to 8 nm. The experimental results are compared with theories considering both intrinsic phonon-phonon interactions and extrinsic surface roughness scattering including a wavelength-dependent specularity. Our results provide insight to understand some of the limits of nanomechanical resonators and thermal transport in nanostructures

CO21 234. Implantación trans apical de válvula aórtica: excelentes resultados en pacientes de alto riesgo

ObjetivosLa implantación transapical de válvulas aórticas es un método nuevo aplicable a pacientes de alto riesgo y estenosis grave de válvula aórtica. Un informe de nuestra experiencia inicial.MétodosDesde abril de 2008 fueron tratados 208 pacientes (edad 79±8 anos, media 36-99 años), con el método híbrido de implantación transapical de válvula aórtica. La media logística EuroSCORE (STS) fue de 40±20% (6-97%) y la media del STS score 21±16% (3-97%). Catorce pacientes ingresaron en shock cardiogénico. Operaciones combinadas fueron efectuadas en 30 pacientes. Intervención de coronarias con stent en 25 pacientes, corrección de ASD en un paciente, dilatación de estenosis pulmonar en un paciente. Aneurismectomía en dos pacientes.Implantación de stent en la arteria renal en un paciente.ResultadosEl éxito técnico de las operaciones fue del 99,5%, la mortalidad hospitalaria fue de 5,7% para todo el grupo, 21% para el grupo en shock cardiogénico. No hubo complicaciones neurológicas en ningún paciente. En el 6% de los pacientes operados hubo la necesidad de implantación de marcapasos. El análisis de regresión univariante demuestra que el shock cardiogénico, elevado B-type natriuretic peptide (BNP)-level, son claros indicadores para la mortalidad postoperatoria temprana (30 días después de la operación). Shock cardiogénico, New York Heart Association (NYHA) IV, altos scores de riesgo, insuficiencia renal grave, son factores independientes para la predicción de la mortalidad acumulativa.ConclusionesLa técnica de recambio transapical de válvulas aórticas reduce significativamente el riesgo operatorio en pacientes de alto riesgo en comparación con el método convencional de recambio valvular aórtico

A possible origin of superconducting currents in cosmic strings

The scattering and capture of right-handed neutrinos by an Abelian cosmic string in the SO(10) grand unification model are considered. The scattering cross-section of neutrinos per unit length due to the interaction with the gauge and Higgs fields of the string is much larger in its scaling regime than in the friction one because of the larger infrared cutoff of the former.The probability of capture in a zero mode of the string accompanied by the emission of a gauge or Higgs boson shows a resonant peak for neutrino momentum of the order of its mass. Considering the decrease of number of strings per unit comoving volume in the scaling epoch the cosmological consequences of the superconducting strings formed in this regime will be much smaller than those which could be produced already in the friction one.Comment: 14 pages Latex, 4 figues/ep

Constraining Stellar Rotation at the Zero-Age Main Sequence with TESS

The zero-age main sequence (ZAMS) is a critical phase for stellar angular momentum evolution, as stars transition from contraction-dominated spin-up to magnetic wind-dominated spin-down. We present the first robust observational constraints on rotation for FGK stars at $\approx40$ Myr. We have analyzed TESS light curves for 1410 members of five young open clusters with ages between 25-55 Myr: IC 2391, IC 2602, NGC 2451A, NGC 2547, and Collinder 135. In total, we measure 868 rotation periods, including 96 new, high-quality periods for stars around 1 ${M_{\odot}}$. This is an increase of ten times the existing literature sample at the ZAMS. We then use the $\tau^2$ method to compare our data to models for stellar angular momentum evolution. Although the ages derived from these rotation models do not match isochronal ages, we show these observations can clearly discriminate between different models for stellar wind torques. Finally, $\tau^2$ fits indicate that magnetic braking and/or internal angular momentum transport significantly impact rotational evolution even on the pre-main sequence.Comment: 20 pages, 11 figures, 4 tables; ApJ Accepte

Constitutive expression of selected genes from the pentose phosphate and aromatic pathways increases the shikimic acid yield in high-glucose batch cultures of an Escherichia coli strain lacking PTS and pykF

BACKGROUND: During the last two decades many efforts have been directed towards obtaining efficient microbial processes for the production of shikimic acid (SA); however, feeding high amounts of substrate to increase the titer of this compound has invariably rendered low conversion yields, leaving room for improvement of the producing strains. In this work we report an alternative platform to overproduce SA in a laboratory-evolved Escherichia coli strain, based on plasmid-driven constitutive expression of six genes selected from the pentose phosphate and aromatic amino acid pathways, artificially arranged as an operon. Production strains also carried inactivated genes coding for phosphotransferase system components (ptsHIcrr), shikimate kinases I and II (aroK and aroL), pyruvate kinase I (pykF) and the lactose operon repressor (lacI). RESULTS: The strong and constitutive expression of the constructed operon permitted SA production from the beginning of the cultures, as evidenced in 1 L batch-mode fermentors starting with high concentrations of glucose and yeast extract. Inactivation of the pykF gene improved SA production under the evaluated conditions by increasing the titer, yield and productivity of this metabolite compared to the isogenic pykF(+) strain. The best producing strain accumulated up to 43 g/L of SA in 30 h and relatively low concentrations of acetate and aromatic byproducts were detected, with SA accounting for 80% of the produced aromatic compounds. These results were consistent with high expression levels of the glycolytic pathway and synthetic operon genes from the beginning of fermentations, as revealed by transcriptomic analysis. Despite the consumption of 100 g/L of glucose, the yields on glucose of SA and of total aromatic compounds were about 50% and 60% of the theoretical maximum, respectively. The obtained yields and specific production and consumption rates proved to be constant with three different substrate concentrations. CONCLUSIONS: The developed production system allowed continuous SA accumulation until glucose exhaustion and eliminated the requirement for culture inducers. The obtained SA titers and yields represent the highest reported values for a high-substrate batch process, postulating the strategy described in this report as an interesting alternative to the traditionally employed fed-batch processes for SA production

Prophylactic properties of a Leishmania-specific hypothetical protein in a murine model of visceral leishmaniasis

In this work, the effect of vaccination of a newly described Leishmania infantum antigenic protein has been studied in BALB/c mice infected with this parasite species. The LiHyD protein was characterized after a proteomic screening performed with the sera from dogs suffering visceral leishmaniasis (VL). Its recombinant version was expressed, purified and administered to BALB/c mice in combination with saponin. As a result of vaccination and 10 weeks after challenge using an infective dose of L. infantum stationary promastigotes, vaccinated mice showed lower parasite burdens in different organs (liver, spleen, bone marrow and footpads' draining lymph nodes) than mice inoculated with the adjuvant alone or the vaccine diluent. Protected mice showed anti-Leishmania IgG2a antibodies and a predominant IL-12-driven IFN-γ production (mainly produced by CD4 T cells) against parasite proteins, whereas unprotected controls showed anti-Leishmania IgG1 antibodies and parasite-mediated IL-4 and IL-10 responses. Vaccinated mice showed an anti-LiHyD IgG2a humoral response, and their spleen cells were able to secrete LiHyD-specific IFN-γ, IL-12 and GM-CSF cytokines before and after infection. The protection was correlated with the Leishmania-specific production on nitric oxide. Altogether, the results indicate that the new LiHyD protein could be considered in vaccine formulations against VL.Instituto Nacional de Ci^encia e Tecnologia em Nano-biofarmac^eutica (INCT-NanoBiofar), FAPEMIG (CBB-APQ-00819-12 and CBB-APQ-01778-2014) and CNPq (APQ-482976/2012-8, APQ-488237/2013-0 and APQ-467640/2014-9). In addition, this study was partially funded by the Spanish grant from Ministerio de Economía y Competitividad-FEDER (FIS PI14/00366 from the Instituto de Salud Carlos III)Peer Reviewe

A Leishmania-specific hypothetical protein expressed in both promastigote and amastigote stages of Leishmania infantum employed for the serodiagnosis of, and as a vaccine candidate against, visceral leishmaniasis

Background: LiHyV is an antigenic hypothetical protein present in both promastigote and amastigote stages of Leishmania infantum, which was recently identified by an immunoproteomic approach. A recombinant version of this protein (rLiHyV) was evaluated as a diagnostic marker for canine VL (CVL). In addition, the prophylactic efficacy of the rLiHyV protein, and two of its CD8+ T cell epitopes, has been analyzed in a murine model of visceral leishmaniasis (VL). Methods: Initially, the rLiHyV protein was evaluated by an ELISA technique for the serodiagnosis of CVL. Secondly, vaccines composed of the recombinant protein and both chemically synthesized peptides, combined with saponin as an adjuvant; were administered subcutaneously into BALB/c mice. The cellular and humoral responses generated by vaccination were evaluated. In addition, the parasite burden and immune response were studied 10 weeks after L. infantum infection. Results: The rLiHyV protein was recognized by antibodies of VL dogs. No cross-reactivity was obtained with sera from dogs vaccinated with a Brazilian commercial vaccine, with sera from animals infected with Trypanosoma cruzi, Babesia canis and Ehrlichia canis, or those from non-infected animals living in an endemic area for leishmaniasis. After challenge with L. infantum, spleen cells of BALB/c mice vaccinated with rLiHyV/saponin stimulated with parasite antigens showed a higher production of IFN-γ, IL-12 and GM-CSF, than the same cells obtained from mice vaccinated with the individual peptides, or mice from control (inoculated with saline or saponin) groups. This Th1-type cellular response observed in rLiHyV/saponin vaccinated mice was accompanied by the induction of parasite-specific IgG2a isotype antibodies. Animals immunized with rLiHyV/saponin showed significant reductions in the parasite burden in the liver, spleen, bone marrow and in the lymph nodes draining the paws relative to control mice. Conclusions: The present study showed for the first time that the L. infantum LiHyV protein could be considered as a vaccine candidate against L. infantum infection, as well as a diagnostic marker for CVL.This work was supported by grants from Instituto Nacional de Ciência e Tecnologia em Nanobiofarmacêutica (INCT-Nanobiofar), FAPEMIG (CBB-APQ-00819-12), and CNPq (APQ-472090/2011-9, RHAE-456287/2012-4, APQ-482976/2012-8, and APQ-488237/2013-0). MACF is a grant recipient of FAPEMIG/CAPES. EAFC and APF are grant recipient of CNPq.Peer Reviewe

PREVALENCIA DE Giardia sp. EN Canis familiaris DE LOS DISTRITOS DE LA PROVINCIA CONSTITUCIONAL DEL CALLAO

El objetivo de este trabajo fue determinar la prevalencia de Giardia sp. en la población canina doméstica de los 6 distritos que conforman la Provincia Constitucional del Callao. Se colectaron 385 muestras fecales de perros, aparentemente normales, de ambos sexos, de diferentes edades y de acuerdo a la zona en donde habitaban sus propietarios. Las muestras fueron procesadas mediante la técnica de sedimentación espontánea encontrándose una prevalencia de 9.4 ± 2% de Giardia sp. Se cuantificó la asociación entre la presencia del parásito y las características físicas de las heces, estrato distrital de procedencia, sexo y edad del canino mediante la prueba de regresión logística, determinándose una relación estadísticamente significativa entre el hallazgo de quistes de Giardia sp. y las características físicas de las muestras. Los resultados denotan una parasitosis moderada de Giardia sp. en los caninos, evidenciando un riesgo zoonótico, por lo que se hace necesario el establecimiento de programas educativos para prevenir la posibilidad de contagio, especialmente en la población infantil.The aim of this study was to determine the Giardia sp. prevalence in household dog populations on the six districts of the Provincia Constitucional del Callao. Fecal samples were collected from 385 apparently healthy dogs of various ages and processed by the spontaneous sedimentation technique. The results indicated the 9.4 ± 2% (36/385) of the canine population were positive to Giardia sp. cysts. Relationships between cysts detection and fecal samples characteristics, and origin, sex and age of dogs were analyzed by logistic regression. A significant statistical relationship was found between Giardia sp. detection and physical characteristics of fecal samples. Results show a moderate Giardia sp. infection in dogs which evidences a zoonotic risk that highlight the necessity of setting up educational programmes in order to prevent Giardia sp. Transmission, especially to infant population