2,447 research outputs found

    Osteogenic effects of simvastatin-loaded mesoporous titania thin films

    Get PDF
    The use of statins in the field of bone regeneration is under current investigation due to the existing demand for non-toxic anabolic agents capable of enhancing bone formation in cases of substantial loss. Simvastatin, a coenzyme currently prescribed in clinics to inhibit cholesterol biosynthesis, has been proven to promote osteogenic differentiation by stimulating bone formation and inhibiting osteoclasts activity. We present the loading of simvastatin in mesoporous TiO2 thin films toward combining the pro-osteogenic properties of this molecule with the demonstrated bioactivity of titania. TiO2 thin films processing and characterization were carried out, as well as evaluation of MC3T3-E1 pre-osteoblasts viability when directly incubated with different concentrations of simvastatin, followed by the analysis of osteogenic activity promoted by simvastatin upon loading in the thin films. The accessible porosity of 36% quantified on the 95 ± 5 nm thick mesoporous thin films, together with pore diameters of 5.5 nm, necks between pores of 2.8 nm and interpore distances of 12 ± 2 nm allow the loading of the simvastatin molecule, as confirmed by FTIR spectroscopy. Simvastatin was found to promote MC3T3-E1 pre-osteoblasts viability at concentrations ≤0.01 g l−1, with a cytotoxicity threshold of 0.05 g l−1. We additionally found that film loadings with 0.001 g l−1 simvastatin promotes statistically higher MC3T3-E1 pre-osteoblast proliferation whereas a higher concentration of 0.01 g l−1 leads to statistically higher osteogenic activity (ALP synthesis), after 21 days of incubation, as compared to unloaded films. These results demonstrate the potential of simvastatin local administration based on bioactive mesoporous thin films to promote pro-osteogenic properties. By focusing this strategy on the coating of metallic prostheses, the supply of simvastatin to the target tissue can be favored and risks of systemic side effects will be reduced while enhancing the osteointegration of the implants.Fil: Lopez Alvarez, Miriam. Universidad de Vigo; EspañaFil: López Puente, Vanesa. Universidad de Vigo; EspañaFil: Rodriguez Valencia, Cosme. Universidad de Vigo; EspañaFil: Angelome, Paula Cecilia. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Liz Marzan, Luis M. Ikerbasque; EspañaFil: Serra, Julia. Universidad de Vigo; EspañaFil: Pastoriza Santos, Isabel. Universidad de Vigo; EspañaFil: Gonzalez, Pio. Universidad de Vigo; Españ

    Identification of Cellular Genes Targeted by KSHV-Encoded MicroRNAs

    Get PDF
    MicroRNAs (miRNAs) are 19 to 23 nucleotide–long RNAs that post-transcriptionally regulate gene expression. Human cells express several hundred miRNAs which regulate important biological pathways such as development, proliferation, and apoptosis. Recently, 12 miRNA genes have been identified within the genome of Kaposi sarcoma–associated herpesvirus; however, their functions are still unknown. To identify host cellular genes that may be targeted by these novel viral regulators, we performed gene expression profiling in cells stably expressing KSHV-encoded miRNAs. Data analysis revealed a set of 81 genes whose expression was significantly changed in the presence of miRNAs. While the majority of changes were below 2-fold, eight genes were down-regulated between 4- and 20-fold. We confirmed miRNA-dependent regulation for three of these genes and found that protein levels of thrombospondin 1 (THBS1) were decreased >10-fold. THBS1 has previously been reported to be down-regulated in Kaposi sarcoma lesions and has known activity as a strong tumor suppressor and anti-angiogenic factor, exerting its anti-angiogenic effect in part by activating the latent form of TGF-β. We show that reduced THBS1 expression in the presence of viral miRNAs translates into decreased TGF-β activity. These data suggest that KSHV-encoded miRNAs may contribute directly to pathogenesis by down-regulation of THBS1, a major regulator of cell adhesion, migration, and angiogenesis

    Partitioning Transcript Variation in Drosophila: Abundance, Isoforms, and Alleles

    Get PDF
    Multilevel analysis of transcription is facilitated by a new array design that includes modules for assessment of differential expression, isoform usage, and allelic imbalance in Drosophila. The ∼2.5 million feature chip incorporates a large number of controls, and it contains 18,769 3′ expression probe sets and 61,919 exon probe sets with probe sequences from Drosophila melanogaster and 60,118 SNP probe sets focused on Drosophila simulans. An experiment in D. simulans identified genes differentially expressed between males and females (34% in the 3′ expression module; 32% in the exon module). These proportions are consistent with previous reports, and there was good agreement (κ = 0.63) between the modules. Alternative isoform usage between the sexes was identified for 164 genes. The SNP module was verified with resequencing data. Concordance between resequencing and the chip design was greater than 99%. The design also proved apt in separating alleles based upon hybridization intensity. Concordance between the highest hybridization signals and the expected alleles in the genotype was greater than 96%. Intriguingly, allelic imbalance was detected for 37% of 6579 probe sets examined that contained heterozygous SNP loci. The large number of probes and multiple probe sets per gene in the 3′ expression and exon modules allows the array to be used in D. melanogaster and in closely related species. The SNP module can be used for allele specific expression and genotyping of D. simulans

    Tumor Associated Stromal Cells Play a Critical Role on the Outcome of the Oncolytic Efficacy of Conditionally Replicative Adenoviruses

    Get PDF
    The clinical efficacy of conditionally replicative oncolytic adenoviruses (CRAd) is still limited by the inefficient infection of the tumor mass. Since tumor growth is essentially the result of a continuous cross-talk between malignant and tumor-associated stromal cells, targeting both cell compartments may profoundly influence viral efficacy. Therefore, we developed SPARC promoter-based CRAds since the SPARC gene is expressed both in malignant cells and in tumor-associated stromal cells. These CRAds, expressing or not the Herpes Simplex thymidine kinase gene (Ad-F512 and Ad(I)-F512-TK, respectively) exerted a lytic effect on a panel of human melanoma cells expressing SPARC; but they were completely attenuated in normal cells of different origins, including fresh melanocytes, regardless of whether cells expressed or not SPARC. Interestingly, both CRAds displayed cytotoxic activity on SPARC positive-transformed human microendothelial HMEC-1 cells and WI-38 fetal fibroblasts. Both CRAds were therapeutically effective on SPARC positive-human melanoma tumors growing in nude mice but exhibited restricted efficacy in the presence of co-administered HMEC-1 or WI-38 cells. Conversely, co-administration of HMEC-1 cells enhanced the oncolytic efficacy of Ad(I)-F512-TK on SPARC-negative MIA PaCa-2 pancreatic cancer cells in vivo. Moreover, conditioned media produced by stromal cells pre-infected with the CRAds enhanced the in vitro viral oncolytic activity on pancreatic cancer cells, but not on melanoma cells. The whole data indicate that stromal cells might play an important role on the outcome of the oncolytic efficacy of conditionally replicative adenoviruses.Facultad de Ciencias Veterinaria

    Susceptibility patterns and molecular identification of Trichosporon species

    Get PDF
    The physiological patterns, the sequence polymorphisms of the internal transcriber spacer (ITS), and intergenic spacer regions (IGS) of the rRNA genes and the antifungal susceptibility profile were evaluated for their ability to identify Trichosporon spp. and their specificity for the identification of 49 clinical isolates of Trichosporon spp. Morphological and biochemical methodologies were unable to differentiate among the Trichosporon species. ITS sequencing was also unable to differentiate several species. However, IGS1 sequencing unambiguously identified all Trichosporon isolates. Following the results of DNA-based identification, Trichosporon asahii was the species most frequently isolated from deep sites (15 of 25 strains; 60%). In the main, other Trichosporon species were recovered from cutaneous samples. The majority of T. asahii, T. faecale, and T. coremiiforme clinical isolates exhibited resistance in vitro to amphotericin B, with geometric mean (GM) MICs >4 mug/ml. The other species of Trichosporon did not show high MICs of amphotericin B, and GM MICs were <1 mug/ml. Azole agents were active in vitro against the majority of clinical strains. The most potent compound in vitro was voriconazole, with a GM MIC </=0.14 mug/ml. The sequencing of IGS correctly identified Trichosporon isolates; however, this technique is not available in many clinical laboratories, and strains should be dispatched to reference centers where these complex methods are available. Therefore, it seems to be more practical to perform antifungal susceptibility testing of all isolates belonging to Trichosporon spp., since correct identification could take several weeks, delaying the indication of an antifungal agent which exhibits activity against the infectious strain.S

    Inventory of some families of Hemiptera, Coleoptera (Curculionidae) and Hymenoptera associated with horticultural production of the Alto Valle de Río Negro and Neuquén provinces (Argentina)

    Get PDF
    The knowledge of the entomological fauna in productive systems is important for the agroecological management since beneficial insects are a key resource for pest management in horticultural systems. Scientific information on the biodiversity present in a given area is essential as well as the ecological function and/or feeding habits of the insects. In Alto Valle de Río Negro and Neuquén, horticultural production systems can be described as highly dependent on chemical inputs for pest management and fertilization. The aim of this study is to carry out an inventory of the biodiversity of some families of Hemiptera, Coleoptera (Curculionidae) and Hymenoptera present in peri-urban and rural farms located in Neuquén and Río Negro, respectively. Insects were collected through pitfall and sweeping net on tomato and pepper crops and the surrounding non-cultivated areas. Idiosystatus Berg (Auchenorrhyncha) was cited for the first time from Argentina. Species cited for the first time from Neuquén: Hemiptera: Auchenorrhyncha: Acanalonia chloris (Berg), Syncharina punctatissima (Signoret), Amplicephalus dubius Linnavuori, Exitianus obscurinervis (Stål), Agalliana ensigera Oman and Bergallia signata (Stål); Hemiptera: Heteroptera: Harmostes (Harmostes) prolixus Stål and Atrachelus (Atrachelus) cinereus (Fabricius); Coleoptera: Curculionidae: Hypurus bertrandi (Perris), Naupactus leucoloma Boheman, Otiorhynchus rugosostriatus (Goeze) and Sitona discoideus Gyllenhal and Hymenoptera: Xylocopa (Neoxylocopa) augusti Lepeletier and Pseudagapostemon (Neagapostemon) singularis Jörgensen. Species cited for the first time from Río Negro: Hemiptera: Auchenorrhyncha: Amplicephalus dubius Linnavuori, Amplicephalus marginellanus Linnavuori, Circulifer tenellus (Baker) and Xerophloea viridis (Fabricius); Hemiptera: Heteroptera: Tupiocoris cucurbitaceus (Spinola), Atrachelus (Atrachelus) cinereus (Fabricius), Dichelops furcatus (Fabricius) and Harmostes (Harmostes) prolixus Stål; Coleptera: Curculionidae: Naupactus xanthographus (Germar) and Hymenoptera: Diadasia pereyrae (Holmberg) and Dialictus autranellus (Vachal).El conocimiento de la fauna entomológica presente en los sistemas productivos es importante para el manejo agroecológico ya que los insectos beneficiosos son un recurso clave para el manejo de plagas en los sistemas hortícolas. Es esencial contar con información científica sobre la biodiversidad presente en un área determinada y la función ecológica y/o los hábitos alimenticios de los insectos. En el Alto Valle de Río Negro y Neuquén, los sistemas de producción hortícola pueden describirse como altamente dependientes de los insumos químicos para el manejo de plagas y fertilización. El objetivo de este estudio es realizar un inventario de la biodiversidad de algunas familias de Hemiptera, Coleoptera (Curculionidae) e Hymenoptera presentes en las chacras periurbanas y rurales ubicadas en Neuquén y Río Negro, respectivamente. Los insectos fueron recolectados a través de trampas de caída y red entomológica en cultivos de tomate y pimiento, y áreas circundantes no cultivadas. Idiosystatus Berg (Auchenorrhyncha) fue citado por primera vez en Argentina. Especies citadas por primera vez en Neuquén: Hemiptera: Auchenorrhyncha: Acanalonia chloris (Berg), Syncharina punctatissima (Signoret), Amplicephalus dubius Linnavuori, Exitianus obscurinervis (Stål), Agalliana ensigera Oman y Bergallia signata (Stål); Hemiptera: Heteroptera: Harmostes (Harmostes) prolixus Stål y Atrachelus (Atrachelus) cinereus (Fabricius); Coleoptera: (Curculionidae): Hypurus bertrandi (Perris), Naupactus leucoloma Boheman, Otiorhynchus rugosostriatus (Goeze) y Sitona discoideus Gyllenhal e Hymenoptera: Xylocopa (Neoxylocopa) augusti Lepeletier and Pseudagapostemon (Neagapostemon) singularis Jörgensen. Especies citadas por primera vez en Río Negro: Hemiptera: Auchenorrhyncha: Amplicephalus dubius Linnavuori, Amplicephalus marginellanus Linnavuori, Circulifer tenellus (Baker) y Xerophloea viridis (Fabricius); Hemiptera: Heteroptera: Tupiocoris cucurbitaceus (Spinola), Atrachelus (Atrachelus) cinereus (Fabricius), Dichelops furcatus (Fabricius) y Harmostes (Harmostes) prolixus Stål; Coleoptera: Curculionidae: Naupactus xanthographus (Germar) e Hymenoptera: Diadasia pereyrae (Holmberg) y Dialictus autranellus (Vachal).Área Investigación y Desarrollo Tecn. Agricultura Familiar - Región PatagoniaFil: Alvarez, Leopoldo Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Naturales y Museo; ArgentinaFil: Bernardis, Adela M. Universidad Nacional del Comahue. Facultad de Ciencias del Ambiente y la Salud; ArgentinaFil: Defea, Bárbara Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Entomología; ArgentinaFil: Dellapé, Pablo Matías. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Naturales y Museo; ArgentinaFil. Del Río, Maria Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Entomología; ArgentinaFil: Gittins Lopez, Cecilia Gabriela. Instituto Nacional Tecnología Agropecuaria (INTA). Área Investigación y Desarrollo Tecn. Agricultura Familiar - Región Patagonia; ArgentinaFil: Lanteri, Analía A. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Naturales y Museo; ArgentinaFil: López Armengol, María Fernanda. Universidad Nacional del Comahue. Facultad de Ciencias del Ambiente y la Salud; Argentina. Instituto Nacional Tecnología Agropecuaria (INTA). Área Investigación y Desarrollo Tecn. Agricultura Familiar - Región Patagonia; ArgentinaFil: Marino de Remes Lenicov, Ana María. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo; ArgentinaFil: Minghetti, Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Naturales y Museo; ArgentinaFil: Paradell, Susana Liria. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo; Comisión de Investigaciones Científicas de la Provincia de Buenos Aires (CIC PBA); ArgentinaFil: Rizzo, Maria Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

    Acoustically Levitated Whispering-Gallery Mode Microlasers

    Get PDF
    Acoustic levitation has become a crucial technique for contactless manipulation in several fields, particularly in biological applications. However, its application in the photonics field remains largely unexplored. In this study, we implement an affordable and innovative phased-array levitator that enables stable trapping in the air of micrometer dye-doped droplets, thereby enabling the creation of microlasers. For the first time, this paper presents a detailed performance of the levitated microlaser cavity, supported by theoretical analysis concerning the hybrid technology based on the combination of whispering-gallery modes and acoustic fields. The pressure field distribution inside the acoustic cavity is numerically solved and qualitatively matched with the schlieren deflectometry technique. The optical lasing features of the levitated microlasers are highly comparable with those devices based On-a-Chip registering maximum Q-factors of ~ 105, and minimum lasing thresholds ~ 150 nJ cm−2. The emission comb is explained as a sum of multiple individual-supported whispering-gallery modes. The use of novel touchless micrometric lasers, produced with an acoustic levitator brings new technological opportunities based on photonic-acoustic technological platforms

    Tumor Associated Stromal Cells Play a Critical Role on the Outcome of the Oncolytic Efficacy of Conditionally Replicative Adenoviruses

    Get PDF
    The clinical efficacy of conditionally replicative oncolytic adenoviruses (CRAd) is still limited by the inefficient infection of the tumor mass. Since tumor growth is essentially the result of a continuous cross-talk between malignant and tumor-associated stromal cells, targeting both cell compartments may profoundly influence viral efficacy. Therefore, we developed SPARC promoter-based CRAds since the SPARC gene is expressed both in malignant cells and in tumor-associated stromal cells. These CRAds, expressing or not the Herpes Simplex thymidine kinase gene (Ad-F512 and Ad(I)-F512-TK, respectively) exerted a lytic effect on a panel of human melanoma cells expressing SPARC; but they were completely attenuated in normal cells of different origins, including fresh melanocytes, regardless of whether cells expressed or not SPARC. Interestingly, both CRAds displayed cytotoxic activity on SPARC positive-transformed human microendothelial HMEC-1 cells and WI-38 fetal fibroblasts. Both CRAds were therapeutically effective on SPARC positive-human melanoma tumors growing in nude mice but exhibited restricted efficacy in the presence of co-administered HMEC-1 or WI-38 cells. Conversely, co-administration of HMEC-1 cells enhanced the oncolytic efficacy of Ad(I)-F512-TK on SPARC-negative MIA PaCa-2 pancreatic cancer cells in vivo. Moreover, conditioned media produced by stromal cells pre-infected with the CRAds enhanced the in vitro viral oncolytic activity on pancreatic cancer cells, but not on melanoma cells. The whole data indicate that stromal cells might play an important role on the outcome of the oncolytic efficacy of conditionally replicative adenoviruses.Facultad de Ciencias Veterinaria

    Estudio piloto de metilfenidato y entrenamiento a padres en el tratamiento de niños con trastorno por déficit de atención hiperactividad [A pilot study of methylphenidate and parent training in the treatment of children with attention-deficit hiperactivity disorder]

    Get PDF
    Objetivo. Este estudio comunica la eficacia de un programa de entrenamiento a padres y un ensayo clínico con medicación estimulante (metilfenidato), en la disminución de síntomas de trastorno por déficit de atención-hiperactividad (TDAH) en una muestra de niños venezolanos.Pacientes y métodos. 24 niños, con edades entre 6 y 10 años, con diagnóstico de TDAH, identificados en unas jornadas de cribado de TDAH, se asignaron aleatoriamente a los dos grupos de tratamiento: entrenamiento a padres y medicación estimulante (metilfenidato).Resultados. Ambos grupos mostraron reducción de síntomas al finalizar la fase de intervención terapéutica en diferentes grados. Estas diferencias fueron estadísticamente significativas para las valoraciones de los padres en ambos grupos, en los síntomas de falta de atención, hiperactividad e impulsividad. Las valoraciones de los profesores mostraron disminución de síntomas significativos en el grupo de medicación para las medidas de hiperactividad e impulsividad, pero no para las de falta de atención, mientras que para el grupo de entrenamiento a padres sólo hubo diferencias significativas en el índice de TDAH. No hubo diferencia en cuanto a la efectividad de ambas intervenciones.Conclusiones. Al comparar ambos programas de tratamiento, se observa que tanto el entrenamiento a padres como la medicación psicoestimulante son tratamientos efectivos para la disminución de los síntomas del TDAH. A pesar de que no existen diferencias entre la efectividad de ambas intervenciones, se observa una tendencia a que la medicación sea más efectiva. - OBJECTIVE. This study gives information about a parent training program and a clinical trial with a stimulant drug (methylphenidate) to reduce the symptoms of attention deficit hiperactivity disorder (ADHD) in a group of children in Venezuela.PATIENTS AND METHODS. 24 children, aged between 6 and 10 years and diagnosed as having ADHD, identified in ADHD screening days, were randomly assigned to two groups of treatment: parent training and a stimulant drug (methylphenidate).RESULTS. Both groups showed an improvement in their symptoms, to different degrees, after treatment. The differences were statistically significant, as evaluated by their parents, regarding the symptoms of inattention, hyperactivity and impulsivity. The teachers observed a significant improvement for the medication group with respect to the symptoms of hyperactivity and impulsivity, but no change in the inattention, whilst in the parent training group there was only significant difference in the ADHD index. There was no difference in the effectiveness of the two types of treatment.CONCLUSIONS. When the two programs of treatment were compared it was observed that both parent training and psychostimulant medication were effective in reducing the symptoms of ADHD. Although there was no difference in the effectiveness of the two programs, there was a tendency for medication to be more effectiv
    corecore