The nucleotidohydrolases DCTPP1 and dUTPase are involved in the cellular response to decitabine

Decitabine (5-aza-2acute;-deoxycytidine, aza-dCyd) is an anticancer drug used clinically for the treatment of myelodysplastic syndromes and acute myeloid leukemia that can act as a DNA-demethylating or genotoxic agent in a dose-dependent manner. On the other hand, DCTPP1 and dUTPase are two "house-cleaning" nucleotidohydrolases involved in the elimination of non-canonical nucleotides. Here we show that exposure of HeLa cells to decitabine up-regulates the expression of several pyrimidine metabolic enzymes including DCTPP1, dUTPase, dCMP deaminase and thymidylate synthase thus suggesting their contribution to the cellular response to this anticancer nucleoside. We present several lines of evidence supporting that, in addition to the formation of aza-dCTP, an alternative cytotoxic mechanism for decitabine may involve the formation of aza-dUMP, a potential thymidylate synthase inhibitor. Indeed, dUTPase or DCTPP1 down-regulation enhanced the cytotoxic effect of aza-dCyd producing an accumulation of nucleoside triphosphates containing uracil as well as uracil misincorporation and double-strand breaks in genomic DNA. Moreover, DCTPP1 hydrolyzes the triphosphate form of decitabine with similar kinetic efficiency than its natural substrate dCTP and prevents decitabine-induced global DNA demethylation. The data suggest that the nucleotidohydrolases DCTPP1 and dUTPase are factors involved in the mode of action of decitabine with potential value as enzymatic targets to improve decitabine-based chemotherapy

Binary frequency of planet-host stars at wide separations: A new brown dwarf companion to a planet-host star

The aim of the project is to improve our knowledge on the multiplicity of planet-host stars at wide physical separations. We cross-matched approximately 6200 square degree area of the Southern sky imaged by the Visible Infrared Survey Telescope for Astronomy (VISTA) Hemisphere Survey (VHS) with the Two Micron All Sky Survey (2MASS) to look for wide common proper motion companions to known planet-host stars. We complemented our astrometric search with photometric criteria. We confirmed spectroscopically the co-moving nature of seven sources out of 16 companion candidates and discarded eight, while the remaining one stays as a candidate. Among these new wide companions to planet-host stars, we discovered a T4.5 dwarf companion at 6.3 arcmin (~9000 au) from HIP70849, a K7V star which hosts a 9 Jupiter mass planet with an eccentric orbit. We also report two new stellar M dwarf companions to one G and one metal-rich K star. We infer stellar and substellar binary frequencies for our complete sample of 37 targets of 5.4+/-3.8% and 2.7+/-2.7% (1 sigma confidence level), respectively, for projected physical separations larger than ~60-160 au assuming the range of distances of planet-host stars (24-75 pc). These values are comparable to the frequencies of non planet-host stars. We find that the period-eccentricity trend holds with a lack of multiple systems with planets at large eccentricities (e > 0.2) for periods less than 40 days. However, the lack of planets more massive than 2.5 Jupiter masses and short periods (<40 days) orbiting single stars is not so obvious due to recent discoveries by ground-based transit surveys and space missions.Comment: Accepted for publication in A&A, 13 pages, 5 figures, 3 tables, optical spectra will be available at CDS Strasbour

Multicorporalidad frente a ocularcentrismo: de la ciudad ojo-individuo a la ciudad sensorial-participada

Algunos autores/as, como Jay (1988, 2003, 2007, 2008), Levin (1988, 1993) o Jenks (1995), han investigado acerca de la influencia del ocularcentrismo en la cultura occidental. Otros/as, como Pallasmaa (2006), han especificado esta influencia en el ámbito arquitectónico y urbanístico. Finalmente, a partir de la década de los ochenta, la antropología sensorial cuestionó el visualismo del pensamiento y cultura occidentales, haciendo hincapié en trascender este sesgo con el fin de conectar con la experiencia cultural de los sujetos no occidentales. Sin embargo, y atendiendo a los avances en esta última disciplina, las taxonomías de los sentidos en las culturas responden a un orden cultural y social determinado por la asignación de mayor o menor valor a nuestros sentidos. ¿Y si cuestionamos dicha taxonomía ocularcéntrica dentro de nuestra propia cultura occidental, valiéndonos de las experiencias de los cuerpos que resisten a dicha jerarquización? En este artículo se analiza cómo se gestó el ocularcentrismo en la Modernidad y cómo continúa siendo el principal paradigma en la construcción de las ciudades. Más tarde, atendiendo al desmontaje de dichas taxonomías de la mano de la antropología sensorial y utilizando la multiplicidad de tecnologías que en nuestro tiempo permiten la sinestesia e interdependencia de los sentidos, se presenta un proyecto multisensorial para habitar la ciudad. Este proyecto tiene por objetivo facilitar a los participantes habitar los espacios urbanos de maneras diversas, alejadas de las formas normalizadas de interacción. Certain authors, such as Jay (1988, 2003, 2007, 2008), Levin (1988, 1993) and Jenks (1995), have investigated the influence of ocular-centrism in Western culture. Others such as Pallasmaa (2006) have specifically considered this influence in the architectural and planning context. Finally and since the 1980s, sensory anthropology has questioned the visualism of Western thought and culture, emphasising a need to transcend this bias in order to connect with the cultural experience of non-Western subjects. However, and taking into account the advances of the latter field, cultural taxonomies of the senses follow a cultural and social order that is determined by the assignment of greater or lesser value to our senses. But we may use the experience of bodies that resist this hierarchical process to question the ocular-centric taxonomy present in our own Western culture. This article analyses how ocular-centrism was managed in modernity and how it remains the main paradigm in the construction of the cities. The paper then presents a multisensorial project for inhabiting cities based on the dismantling of said taxonomies through sensory anthropology, making use of the range of contemporary technologies that permit synaesthesia and the interdependence of our senses. The aim of this project is to enable participants to inhabit urban spaces in diverse ways that differ from the normalised forms of interaction

Hysteroscopic Management of an Interstitial Ectopic Pregnancy

We report a case of an interstitial ectopic pregnancy successfully managed by hysteroscopy. We highlight the benefits of using hysteroscopy, a non-invasive procedure, to preserve fertility

Science with an ngVLA: Resolving the Radio Complexity of EXor and FUor-type Systems with the ngVLA

Episodic accretion may be a common occurrence in the evolution of young pre-main sequence stars and has important implications for our understanding of star and planet formation. Many fundamental aspects of what drives the accretion physics, however, are still unknown. The ngVLA will be a key tool in understanding the nature of these events. The high spatial resolution, broad spectral coverage, and unprecedented sensitivity will allow for the detailed analysis of outburst systems. The proposed frequency range of the ngVLA allows for observations of the gas, dust, and non-thermal emission from the star and disk.Comment: 8 pages, 1 figure, To be published in the ASP Monograph Series, "Science with a Next-Generation VLA", ed. E. J. Murphy (ASP, San Francisco, CA

Novel efficient genome-wide SNP panels for the conservation of the highly endangered Iberian lynx

Background: The Iberian lynx (Lynx pardinus) has been acknowledged as the most endangered felid species in the world. An intense contraction and fragmentation during the twentieth century left less than 100 individuals split in two isolated and genetically eroded populations by 2002. Genetic monitoring and management so far have been based on 36 STRs, but their limited variability and the more complex situation of current populations demand more efficient molecular markers. The recent characterization of the Iberian lynx genome identified more than 1.6 million SNPs, of which 1536 were selected and genotyped in an extended Iberian lynx sample. Methods: We validated 1492 SNPs and analysed their heterozygosity, Hardy-Weinberg equilibrium, and linkage disequilibrium. We then selected a panel of 343 minimally linked autosomal SNPs from which we extracted subsets optimized for four different typical tasks in conservation applications: individual identification, parentage assignment, relatedness estimation, and admixture classification, and compared their power to currently used STR panels. Results: We ascribed 21 SNPs to chromosome X based on their segregation patterns, and identified one additional marker that showed significant differentiation between sexes. For all applications considered, panels of autosomal SNPs showed higher power than the currently used STR set with only a very modest increase in the number of markers. Conclusions: These novel panels of highly informative genome-wide SNPs provide more powerful, efficient, and flexible tools for the genetic management and non-invasive monitoring of Iberian lynx populations. This example highlights an important outcome of whole-genome studies in genetically threatened species

Mice with Infectious Colitis Exhibit Linear Growth Failure and Subsequent Catch-Up Growth Related to Systemic Inflammation and IGF-1

In developing communities, intestinal infection is associated with poor weight gain and linear-growth failure. Prior translational animal models have focused on weight gain investigations into key contributors to linear growth failure have been lacking. We hypothesized that murine intestinal infection with Citrobacter-rodentium would induce linear-growth failure associated with systemic inflammation and suppressed serum levels of insulin-like growth factor-1 (IGF-1). We evaluated 4 groups of mice infected or sham-infected on day-of-life 28: uninfected-controls, wild-type C.-rodentium-infected, partially-attenuated C. rodentium-infected (with deletion of 3 serine protease genes involved in colonization), and pair-fed (given the amount of daily food consumed by the wild-type C.-rodentium group). Relative to the uninfected group, mice infected with wild-type C.-rodentium exhibited temporal associations of lower food intake, weight loss, linear-growth failure, higher IL-6 and TNF-α and lower IGF-1. However, relative to the pair-fed group, the C.-rodentium-infected group only differed significantly by linear growth and systemic inflammatory cytokines. Between post-infection days 15–20, the infected group exhibited resolution of systemic inflammation. Between days 16–20, both wild-type C.-rodentium and pair-fed groups exhibited rapid linear-growth velocities exceeding the uninfected and mutant C.-rodentium groups; during this time levels of IGF-1 increased to match the uninfected group. We submit this as a model providing important opportunities to study mechanisms of catch-up growth related to intestinal inflammation. We conclude that in addition to known effects of weight loss, infection with C.-rodentium induces linear-growth failure potentially related to systemic inflammation and low levels of IGF-1, with catch-up of linear growth following resolution of inflammation

Observation of a topologically protected state in a magnetic domain wall stabilized by a ferromagnetic chemical barrier

The precise control and stabilization of magnetic domain walls is key for the development of the next generation magnetic nano-devices. Among the multitude of magnetic configurations of a magnetic domain wall, topologically protected states are of particular interest due to their intrinsic stability. In this work, using XMCD-PEEM, we have observed a topologically protected magnetic domain wall in a ferromagnetic cylindrical nanowire. Its structure is stabilized by periodic sharp alterations of the chemical composition in the nanowire. The large stability of this topologically protected domain wall contrasts with the mobility of other non-protected and non-chiral states also present in the same nanowire. The micromagnetic simulations show the structure and the conditions required to find the topologically protected state. These results are relevant for the design of future spintronic devices such as domain wall based RF oscillators or magnetic memories

Molecular and clinical analysis of Ellis-van Creveld syndrome in the United Arab Emirates

<p>Abstract</p> <p>Background</p> <p>Ellis-van Creveld (EvC) syndrome is an autosomal recessive chondrodysplastic condition with clinical manifestations that include short-limbs and ribs, postaxial polydactyly and dysplastic nails and teeth. In about two thirds of patients, mutations in either <it>EVC </it>or <it>EVC2 </it>genes have been found to be the underlying cause.</p> <p>Methods</p> <p>In this paper, we describe the molecular (DNA sequencing) and clinical analysis of six children diagnosed with EvC from four different families from the United Arab Emirates (UAE).</p> <p>Results</p> <p>All the children had the common clinical and radiological features of this syndrome. However, DNA sequence analysis of the genes shown to be involved (<it>EVC </it>and <it>EVC2</it>) revealed a novel splice site mutation (c.2047-1G>T) in intron 13 of <it>EVC2 </it>gene in one family. In addition, we confirm previous mutational analyses that showed a truncating mutation in exon 13 of <it>EVC </it>gene (c.1813C>T; p.Q605X) in the second family and a single nucleotide deletion (c.981delG; p.K327<it>fs</it>) in exon 8 of <it>EVC2 </it>gene in the third family. No mutations in the exons, splice sites or the promoter regions of either gene have been found in the index case of the fourth family who exhibited "EvC-like" features.</p> <p>Conclusions</p> <p>Given the small population size of UAE, our data illustrates further the molecular heterogeneity observed in EvC patients and excludes the possibility of a common founder effect for this condition in the UAE reflecting the current ethnic diversity of the country.</p