Combination of bioanalytical approaches and quantitative proteomics for the elucidation of the toxicity mechanisms associated to TiO2 nanoparticles exposure in human keratinocytes.

Titanium dioxide nanoparticles (TiO2-NPs) are being used in several consumer products. The high refractive index of nano-scaled titanium dioxide particles allows them to protect from UV radiation, and so, they can be found as one of the main components of cosmetics and suncreens. Many studies have reported the potential toxicological effects associated to TiO2-NPs such as ROS generation, DNA damage, apoptosis and cell cycle arrest, among others. The continuous and systematic use of TiO2-NPs in cosmetic products requires a full comprehension of the risks involving their sustained contact with the human skin. Thus, it is important to evaluate not only the hazardous effects but to elucidate the biomolecular mechanisms involved in such effects. Based on this premises, we have evaluated the potential toxicity of TiO2-NPs using a human epithelial cell culture (HaCaT cells) as in-vitro model, together with different bioanalytical approaches and mass spectrometrybased quantitative proteomics, to gain a deeper insight into the molecular mechanisms of toxicity associated to TiO2-NPs exposurepre-print451 K

Genetic and morphological evidence reveals the existence of a new family, genus and species of Echinorhynchida (Acanthocephala)

Gymnorhadinorhynchus gen. n. is proposed to accommodate its type species, G. decapteri sp. n., a parasite of the marine fish Decapterus punctatus (Cuvier), caught from the coastal waters of Brazil. Gymnorhadinorhynchus decapteri sp. n. was morphologically most similar to species of two echinorhynchid families, the Rhadinorhynchidae and the Cavisomidae, particularly in the structure of the proboscis and the absence of somatic spines, respectively. This combination of morphological features made it difficult to assign our specimen to an extant family of the Acanthocephala. Therefore, in order to clarify the systematic placement of G. decapteri, a molecular phylogenetic analysis was performed based on the SSU and LSU rDNA and the mitochondrial cox1 gene sequences obtained for the new taxon and other 26 acanthocephalan species. The results of parsimony and maximum likelihood analyses, using individual, combined and concatenated sequence data, consistently indicate that the specimens do not belong to any known family of the Echinorhynchida. Rather, G. decapteri represents a distinct lineage that is closely related to the Transvenidae, but distantly related to both the Rhadinorhynchidae and the Cavisomidae. Gymnorhadinorhynchidae fam. n. is therefore erected. This newly described family can be distinguished from other families of Echinorhynchida by the combination of the following morphological characters: a proboscis cylindrical with 10 rows of 22?26 hooks, dorsoventral differences in proboscis hooks, basal hooks forming a ring and being abruptly larger than anterior hooks, absence of trunk spines and presence of four tubular cement glands. This combination, in addition to several molecular autapomorphies, justifies the erection of a new genus, Gymnorhadinorhynchus gen. n., in order to accommodate this new species.Fil: Braicovich, Paola Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencia Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Lanfranchi, Ana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencia Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Farber, Marisa Diana. Instituto Nacional de Tecnología Agropecuaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marvaldi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Provincia de Mendoza. Instituto Argentino de Investigaciones de las Zonas Áridas. Universidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas Áridas; ArgentinaFil: Luque, José L.. Universidade Federal Rural Do Rio de Janeiro; BrasilFil: Timi, Juan Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencia Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; Argentin

The T=1 capsid protein of Penicillium chrysogenum virus is formed by a repeated helix-rich core indicative of gene duplication

et al.Penicillium chrysogenum virus (PcV), a member of the Chrysoviridae family, is a double-stranded RNA (dsRNA) fungal virus with a multipartite genome, with each RNA molecule encapsidated in a separate particle. Chrysoviruses lack an extracellular route and are transmitted during sporogenesis and cell fusion. The PcV capsid, based on a T=1 lattice containing 60 subunits of the 982-amino-acid capsid protein, remains structurally undisturbed throughout the viral cycle, participates in genome metabolism, and isolates the virus genome from host defense mechanisms. Using three-dimensional cryoelectron microscopy, we determined the structure of the PcV virion at 8.0 Å resolution. The capsid protein has a high content of rod-like densities characteristic of α-helices, forming a repeated α-helical core indicative of gene duplication. Whereas the PcV capsid protein has two motifs with the same fold, most dsRNA virus capsid subunits consist of dimers of a single protein with similar folds. The spatial arrangement of the α-helical core resembles that found in the capsid protein of the L-A virus, a fungal totivirus with an undivided genome, suggesting a conserved basic fold. The encapsidated genome is organized in concentric shells; whereas the inner dsRNA shells are well defined, the outermost layer is dense due to numerous interactions with the inner capsid surface, specifically, six interacting areas per monomer. The outermost genome layer is arranged in an icosahedral cage, sufficiently well ordered to allow for modeling of an A-form dsRNA. The genome ordering might constitute a framework for dsRNA transcription at the capsid interior and/or have a structural role for capsid stability. Copyright © 2010, American Society for Microbiology. All Rights Reserved.This work was supported by grants from the Spanish Ministry of Science and Innovation (BFU 2008-02328/BMC and S-0505-Mat-0238 to J.L.C. and BIO2008-02361 to J.R.C.) and the NIH Intramural Research Program with support from the Center for Information Technology.Peer Reviewe

Effects of precession versus instabilities on the jets of GRS 1758-258

Aims. The prototypical microquasar GRS 1758-258 exhibits large-scale morphological changes in radio maps over time which have been attributed to the rise of instabilities. Here, we investigate whether these effects could be attributed to jet precession instead. Methods.We used new and archival radio maps to fit a kinematic jet precession model. The value of the parameters thus obtained were analysed in order to get constraints on the physical properties of the GRS 1758-258 system. Their consistency with different theories of the origins for the jet precession, such as Lense-Thirring effect and tidal torques induced by the secondary star, has previously been studied. Alternatively, we also assessed the possibility that observations are compatible with eventual jet instabilities. Results. The new radio data presented here confirm that the large-scale radio morphology of GRS 1758-258 is changing over time. Our study shows that the 18.48 day period could plausibly be ascribed to precession, thus implying a reinterpretation of assumptions made for the orbital period to date. However, the observed structural changes in radio jets cannot be easily attributed to jet precession according to our analysis. In contrast, the growth of instabilities certainly appears to be a more realistic explanation of these effects.Comment: Accepted for publication in Astronomy and Astrophysic

Aplicaciones tecnológicas para la promoción de los recursos turísticos culturales

El uso intensivo por parte del turista de las Nuevas Tecnologías de la Información y las Comunicaciones (NTIC), tanto en la organización como en el desarrollo del viaje, han revolucionado la forma de promocionar un territorio turístico ya que, cualquier destino que pretenda ser competitivo debe actualizar continuamente toda aquella información que pueda ser de interés para el visitante (localización e interpretación de los recursos, horarios de equipamientos y servicios, etc.), especialmente si este pertenece al segmento del turismo cultural, tipología de usuario que demanda gran cantidad de información sobre los recursos de un destino y cuya motivación principal es el disfrute de los bienes culturales. Este turista, consumidor de TIC, se ha transformando en un usuario 2.0, caracterizado por estar altamente conectado y, por tanto, hacer un uso constante de la red mediante su dispositivo móvil, junto a esto ha pasado de ser un mero visualizador a un generador de información en redes sociales, blogs, etc., y colabora de forma activa aportando su opinión sobre el destino mediante los sistemas de reputación on-line. En consecuencia, surge el turista 2.0, que requiere de información del territorio turístico, en el proceso de anticipación (promoción y marketing), experiencia (comunicación) y recreación (búsqueda de más información, publicaciones y recomendaciones) del viaje turístico. Este artículo analiza y clasifica las TIC y, especialmente las de tipo geográfico (TIG), vinculadas con la interpretación, promoción y puesta en explotación turística de recursos culturales. Así, se abordarán tanto herramientas más tradicionales como tecnologías de una actualidad manifiesta en el ámbito de la promoción y puesta en valor del patrimonio cultural.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Vitamin C activates young LINE-1 elements in mouse embryonic stem cells via H3K9me3 demethylation

This work was supported by grants from the Wellcome Trust/Royal Soci‑ ety (101225/Z/13/Z) and MRC (MR/X008487/1) to M.R.B.; and BBSRC (BB/ T000031/1) to M.R.B. and J.M.F.Background Vitamin C (vitC) enhances the activity of 2-oxoglutarate-dependent dioxygenases, including TET enzymes, which catalyse DNA demethylation, and Jumonji-domain histone demethylases. The epigenetic remodelling promoted by vitC improves the efficiency of induced pluripotent stem cell derivation, and is required to attain a ground-state of pluripotency in embryonic stem cells (ESCs) that closely mimics the inner cell mass of the early blastocyst. However, genome-wide DNA and histone demethylation can lead to upregulation of transposable elements (TEs), and it is not known how vitC addition in culture media affects TE expression in pluripotent stem cells. Results Here we show that vitC increases the expression of several TE families, including evolutionarily young LINE-1 (L1) elements, in mouse ESCs. We find that TET activity is dispensable for L1 upregulation, and that instead it occurs largely as a result of H3K9me3 loss mediated by KDM4A/C histone demethylases. Despite increased L1 levels, we did not detect increased somatic insertion rates in vitC-treated cells. Notably, treatment of human ESCs with vitC also increases L1 protein levels, albeit through a distinct, post-transcriptional mechanism. Conclusion VitC directly modulates the expression of mouse L1s and other TEs through epigenetic mechanisms, with potential for downstream effects related to the multiple emerging roles of L1s in cellular function.Wellcome Trust/Royal Society (101225/Z/13/Z)MRC (MR/X008487/1)BBSRC (BB/T000031/1

Integration of Transcriptomics and Metabolomics to Reveal the Molecular Mechanisms Underlying Rhodium Nanoparticles-Based Photodynamic Cancer Therapy

Rhodium nanoparticles have recently been described as promising photosensitizers due to their low toxicity in the absence of near-infrared irradiation, but their high cytotoxicity when irradiated. Irradiation is usually carried out with a laser source, which allows the treatment to be localized in a specific area, thus avoiding undesirable side effects on healthy tissues. In this study, a multi-omics approach based on the combination of microarray-based transcriptomics and mass spectrometry-based untargeted and targeted metabolomics has provided a global picture of the molecular mechanisms underlying the anti-tumoral effect of rhodium nanoparticle-based photodynamic therapy. The results have shown the ability of these nanoparticles to promote apoptosis by suppressing or promoting anti- and pro-apoptotic factors, respectively, and by affecting the energy machinery of tumor cells, mainly blocking the β-oxidation, which is reflected in the accumulation of free fatty acids and in the decrease in ATP, ADP and NAD+ levels.Depto. de Química AnalíticaFac. de Ciencias QuímicasTRUEMinisterio de Ciencia, Innovaciónpu

A new species of Colobomatus (Copepoda, Phylichthyidae) parasitic on Mullus argentinae (Perciformes, Mullidae) from South American Atlantic coast

A new species of Colobomatus Hesse, 1873 is described from pores of the cephalic sensory system and nostrils of Argentine goatfish, Mullus argentinae Hubbs et Marini, 1933 (Perciformes: Mullidae), living along the southwestern Atlantic coast. The fish were collected at different latitudes, stretching from the State of Rio de Janeiro in the north, through Santa Catarina, Rio Grande do Sul (Brazil) to of Mar del Plata (Argentina) in the south. The prevalence of the infection ranged from 42% through 84%. The new species look alike to two other species, parasites of mullids (C. steenstrupi and C. mulli) particularly in the body shape and the number, shape, and ornamentation of cephalic, thoracic, and genital processes. The new species, however, can be readily distinguished by having the central cephalic process shorter than lateral ones, the later being bilobed at tip forked, and a relatively larger abdomen. Furthermore, C. steenstrupi possesses relatively wider trunk processes with rounded tips, a short abdominal dorsal process, and attains a larger size (up to 3.6 mm). C. mulli also differs by having all body processes with forked tips, and relatively shorter sixth thoracic somite and abdominal segments 1?3. This is the third record of a species of Colobomatus in South American Atlantic waters.Fil: Pereira, Aldenice N.. Universidade Federal Rural Do Rio de Janeiro;Fil: Timi, Juan Tomas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Lanfranchi, Ana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Luque, José L.. Universidade Federal Rural Do Rio de Janeiro

CpGcluster: a distance-based algorithm for CpG-island detection

BACKGROUND: Despite their involvement in the regulation of gene expression and their importance as genomic markers for promoter prediction, no objective standard exists for defining CpG islands (CGIs), since all current approaches rely on a large parameter space formed by the thresholds of length, CpG fraction and G+C content. RESULTS: Given the higher frequency of CpG dinucleotides at CGIs, as compared to bulk DNA, the distance distributions between neighboring CpGs should differ for bulk and island CpGs. A new algorithm (CpGcluster) is presented, based on the physical distance between neighboring CpGs on the chromosome and able to predict directly clusters of CpGs, while not depending on the subjective criteria mentioned above. By assigning a p-value to each of these clusters, the most statistically significant ones can be predicted as CGIs. CpGcluster was benchmarked against five other CGI finders by using a test sequence set assembled from an experimental CGI library. CpGcluster reached the highest overall accuracy values, while showing the lowest rate of false-positive predictions. Since a minimum-length threshold is not required, CpGcluster can find short but fully functional CGIs usually missed by other algorithms. The CGIs predicted by CpGcluster present the lowest degree of overlap with Alu retrotransposons and, simultaneously, the highest overlap with vertebrate Phylogenetic Conserved Elements (PhastCons). CpGcluster's CGIs overlapping with the Transcription Start Site (TSS) show the highest statistical significance, as compared to the islands in other genome locations, thus qualifying CpGcluster as a valuable tool in discriminating functional CGIs from the remaining islands in the bulk genome. CONCLUSION: CpGcluster uses only integer arithmetic, thus being a fast and computationally efficient algorithm able to predict statistically significant clusters of CpG dinucleotides. Another outstanding feature is that all predicted CGIs start and end with a CpG dinucleotide, which should be appropriate for a genomic feature whose functionality is based precisely on CpG dinucleotides. The only search parameter in CpGcluster is the distance between two consecutive CpGs, in contrast to previous algorithms. Therefore, none of the main statistical properties of CpG islands (neither G+C content, CpG fraction nor length threshold) are needed as search parameters, which may lead to the high specificity and low overlap with spurious Alu elements observed for CpGcluster predictions