538 research outputs found
Do Alu repeats drive the evolution of the primate transcriptome?
The abundance of Alu elements near broadly expressed genes is best explained by their preferential preservation near housekeeping genes
Activation of the PI3K/mTOR/AKT pathway and survival in solid tumors: systematic review and meta-analysis
This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: Aberrations in the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)/AKT pathway are common in solid tumors. Numerous drugs have been developed to target different components of this pathway. However the prognostic value of these aberrations is unclear. [Methods]: PubMed was searched for studies evaluating the association between activation of the PI3K/mTOR/AKT pathway (defined as PI3K mutation [PIK3CA], lack of phosphatase and tensin homolog [PTEN] expression by immunohistochemistry or western-blot or increased expression/activation of downstream components of the pathway by immunohistochemistry) with overall survival (OS) in solid tumors. Published data were extracted and computed into odds ratios (OR) for death at 5 years. Data were pooled using the Mantel-Haenszel random-effect model. [Results]: Analysis included 17 studies. Activation of the PI3K/mTOR/AKT pathway was associated with significantly worse 5-year survival (OR:2.12, 95% confidence intervals 1.42-3.16, p<0.001). Loss of PTEN expression and increased expression/ activation of downstream components were associated with worse survival. No association between PIK3CA mutations and survival was observed. Differences between methods for assessing activation of the PI3K/mTOR/AKT pathway were statistically significant (p = 0.04). There was no difference in the effect of up-regulation of the pathway on survival between different cancer sites (p = 0.13). [Conclusion]: Activation of the PI3K/AKT/mTOR pathway, especially if measured by loss of PTEN expression or increased expression/activation of downstream components is associated with poor survival. PIK3CA mutational status is not associated with adverse outcome, challenging its value as a biomarker of patient outcome or as a stratification factor for patients treated with agents acting on the PI3K/AKT/mTOR pathway.Work in A.O. lab is supported by grant PI13/01444 from ISCIII and Diputación de Albacete. Work in A.P. lab is supported by the Fundación Científica de la AECC and the Ministry of Economy and Competitiveness (BFU2012-39151) and Red Temática de Investigación Cooperativa en Cáncer. A.O. and A.P. receive support from CRIS Cancer foundation.Peer Reviewe
Magnetothermal Conductivity of Highly Oriented Pyrolytic Graphite in the Quantum Limit
We report on the magnetic field (0TT) dependence of the
longitudinal thermal conductivity of highly oriented pyrolytic
graphite in the temperature range 5 K 20 K for fields parallel to
the axis. We show that shows large oscillations in the
high-field region (B > 2 T) where clear signs of the Quantum-Hall effect are
observed in the Hall resistance. With the measured longitudinal electrical
resistivity we show that the Wiedemann-Franz law is violated in the high-field
regime.Comment: 4 Figures, to be published in Physical Review B (2003
Caracterización Molecular de la Diversidad Fúngica de los Bosques Llucud y Palictahua: Potencialidades en Control Biológico/Molecular Characterization of Diversity Fungic of the Llucud and Palictahua Forests: Potential in Biological Control
Dentro de los microorganismos más abundantes que se pueden encontrar en formaciones ecosistémicas naturales como los bosques andinos del Ecuador se encuentran los hongos microscópicos, los cuales desempeñan funciones cruciales en dichos ecosistemas. Por lo cual el objetivo de esta investigación fue caracterizar molecularmente la diversidad de hongos presentes en los bosques nativos Llucud y Palictahua, estableciendo sus potencialidades de uso en el control biológico de plagas y enfermedades que afectan a los cultivos agrícolas y cuyo control en su mayoría se lo realiza con plaguicidas químicos. Mediante secuenciación de próxima generación (NGS por sus siglas en inglés) de las muestras compuestas de suelo tomadas del horizonte “A” (rizósfera) de cada bosque, se identificaron 56 especies de hongos en Palictahua y 38 en Llucud, presentándose en ambos bosques un total de 6 hongos con importantes potencialidades para su uso en el control biológico, dentro de las cuales se encontraron: Brachyphoris oviparasitica (nematófago), Simplicillium (entomopatógeno y micoparásito), Hamamotoa lignophila (levadura con actividad Killer) en Llucud, y Metarhizium robertsii (entomopatógeno), Brachyphoris oviparasitica (nematófago) y Paraphaeosphaeria parmeliae (micoparásito) en Palictahua. El Bosque Palictahua presentó mayor diversidad de hongos que el bosque Llucud, sin embargo es importante cuidar ambos bosques, pues poseen una gran riqueza microbiana con un sinnúmero de posibilidades de uso en la medicina, industria, biotecnología y otros campos.
Among the most abundant microorganisms that can be found in natural ecosystem formations such as the Andean forests of Ecuador are microscopic fungi, which play crucial roles in these ecosystems. So that the objective of this research was to molecularly characterize the diversity of fungi present in the native forests Llucud and Palictahua, establishing their potential for use in the biological control of pests and diseases that affect agricultural crops and whose control is mostly carried out with chemical pesticides. Through next-generation sequencing (NGS for its acronym in English) of compound samples of soil took from “A” horizon (rhizosphere). 56 species of fungi were identified in Palictahua and 38 in Llucud, presenting in both forests a total of 6 fungi with significant potential for use in biological control, among which were found: Brachyphoris oviparasitica (nematophagous), Simplicillium sp. (entomopathogen and mycoparasite), Hamamotoa lignophila (yeast with Killer activity) in Llucud, and Metarhizium robertsii (entomopathogen), Brachyphoris oviparasitica (nematophagous) and Paraphaeosphaeria parmeliae (mycoparasite) in Palictahua. The Palictahua forest presented greater diversity of fungi than the Llucud forest, however it is important to take care of both forests, since they have a great microbial richness with a myriad of possibilities of use in medicine, industry, biotechnology and other fields.
Palabras clave: Biodiversidad, Microbiota, Plaguicidas.
Keywords: Biodiversity, Microbiota, Pesticides
Antitumor activity of the novel multi-kinase inhibitor EC-70124 in triple negative breast cancer
This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.Disseminated triple negative breast cancer (TNBC) is an incurable disease with limited therapeutic options beyond chemotherapy. Therefore, identification of druggable vulnerabilities is an important aim. Protein kinases play a central role in cancer and particularly in TNBC. They are involved in many oncogenic functions including migration, proliferation, genetic stability or maintenance of stem-cell like properties. In this article we describe a novel multi-kinase inhibitor with antitumor activity in this cancer subtype. EC-70124 is a hybrid indolocarbazole analog obtained by combinatorial biosynthesis of Rebeccamycin and Staurosporine genes that showed antiproliferative effect and in vivo antitumoral activity. Biochemical experiments demonstrated the inhibition of the PI3K/mTOR and JAK/STAT pathways. EC-70124 mediated DNA damage leading to cell cycle arrest at the G2/M phase. Pathway analyses identified several deregulated functions including cell proliferation, migration, DNA damage, regulation of stem cell differentiation and reversion of the epithelial-mesenchymal transition (EMT) phenotype, among others. Combination studies showed a synergistic interaction of EC-70124 with docetaxel, and an enhanced activity in vivo. Furthermore, EC-70124 had a good pharmacokinetic profile. In conclusion these experiments demonstrate the antitumor activity of EC-70124 in TNBC paving the way for the future clinical development of this drug alone or in combination with chemotherapy.Ministry of Economy and Competitiveness of Spain (BFU2012-39151 and RD12/0036/0003 to AP), and the AECC (to AP). Instituto de Salud Carlos III (PI13/01444) ACEPAIN and CRIS Cancer Foundation (to AO). JCM is a recipient of a
Miguel Servet fellowship program (CP12/03073).Peer Reviewe
Enhancing Luminescence and X-ray Absorption Capacity of Eu3+:LaF3 Nanoparticles by Bi3+ Codoping
Bi3+ codoping has been proposed in this work with a twofold objective, namely, enhancing the luminescence emission of Eu3+:LaF3 nanoparticles (NPs) and increasing their X-ray attenuation capacity, with the purpose of obtaining a bimodal bioprobe for luminescence bioimaging and X-ray computed tomography. The synthesis method, reported here for the first time for LaF3 particles, allowed obtaining uniform, nonaggregated NPs using a homogeneous precipitation in polyol medium at room temperature in just 2 h. The simplicity of the synthesis method allows the large-scale production of NPs. LaF3 NPs with different Eu3+ contents were first synthesized to find the critical Eu3+ concentration, producing the highest emission intensity. This concentration was subsequently used to fabricate Bi3+-Eu3+-codoped LaF3 NPs using the same method. The emission intensity of the codoped NPs increased in more than one order of magnitude, thanks to the possibility of excitation through the Bi3+ ¿ Eu3+ energy-transfer band. The luminescence properties of the codoped NPs were analyzed in detail to find the mechanism responsible for the emission enhancement. Finally, it was demonstrated that the high atomic number of Bi3+, higher than that of lanthanides, was an added value of the material because it increased its X-ray attenuation capacity. In summary, the LaF3 NPs codoped with Eu3+ and Bi3+ presented in this work are promising candidates as a bimodal bioprobe for luminescence bioimaging and X-ray computed tomography
Diversity of Zoanthids (Anthozoa: Hexacorallia) on Hawaiian Seamounts: Description of the Hawaiian Gold Coral and Additional Zoanthids
The Hawaiian gold coral has a history of exploitation from the deep slopes and seamounts of the Hawaiian Islands as one of the precious corals commercialised in the jewellery industry. Due to its peculiar characteristic of building a scleroproteic skeleton, this zoanthid has been referred as Gerardia sp. (a junior synonym of Savalia Nardo, 1844) but never formally described or examined by taxonomists despite its commercial interest. While collection of Hawaiian gold coral is now regulated, globally seamounts habitats are increasingly threatened by a variety of anthropogenic impacts. However, impact assessment studies and conservation measures cannot be taken without consistent knowledge of the biodiversity of such environments. Recently, multiple samples of octocoral-associated zoanthids were collected from the deep slopes of the islands and seamounts of the Hawaiian Archipelago. The molecular and morphological examination of these zoanthids revealed the presence of at least five different species including the gold coral. Among these only the gold coral appeared to create its own skeleton, two other species are simply using the octocoral as substrate, and the situation is not clear for the final two species. Phylogenetically, all these species appear related to zoanthids of the genus Savalia as well as to the octocoral-associated zoanthid Corallizoanthus tsukaharai, suggesting a common ancestor to all octocoral-associated zoanthids. The diversity of zoanthids described or observed during this study is comparable to levels of diversity found in shallow water tropical coral reefs. Such unexpected species diversity is symptomatic of the lack of biological exploration and taxonomic studies of the diversity of seamount hexacorals
Neodymium doped lanthanide fluoride nanoparticles as contrast agents for luminescent bioimaging and X-ray computed tomography
The synthesis of uniform neodymium-doped lanthanum trifluoride nanoparticles with lenticular shape and a mean diameter around 45 nm by using a homogeneous precipitation method is reported. The luminescent properties of the synthesized samples in terms of their emission spectra and emission lifetime are analyzed as a function of the Nd content to find the optimum phosphor and its suitability for luminescent imaging in the second biological window. The X-ray attenuation properties of the optimum phosphor are evaluated to investigate their additional ability as contrast agent for X-ray computed tomography. Finally, the colloidal stability of the obtained nanoparticles in physiological medium and their cytotoxicity are also analyzed to assess their aptness for in vivo bioimaging applications.
En este trabajo se ha desarrollado un método de síntesis de nanopartículas uniformes de trifluoruro de lantano dopadas con neodimio, con forma lenticular y un diámetro medio en torno a 45 nm, basado en un proceso de precipitación homogénea en medio acuoso. Las propiedades luminiscentes de las muestras sintetizadas en términos de sus espectros de emisión y tiempo de vida de las emisiones se han analizado en función del contenido de neodimio (Nd) para determinar el nanofósforo óptimo y su idoneidad para la obtención de imágenes luminiscentes en la segunda ventana biológica. Asimismo, se han evaluado las propiedades de atenuación de rayos X del nanofósforo óptimo para valorar su capacidad adicional como agente de contraste para tomografía computarizada de rayos X. Por último, también se han analizado la estabilidad coloidal de las nanopartículas obtenidas en medio fisiológico y su citotoxicidad para determinar su aplicabilidad para la obtención de imágenes biológicas in vivo
Accuracy of Serological Testing for the Diagnosis of Prevalent Neurocysticercosis in Outpatients with Epilepsy, Eastern Cape Province, South Africa
Epilepsy is a significant contributor to morbidity world-wide in persons of all ages. Little is known, however, about its causes. In the developing world, parasitic infections of the brain, in particular Taenia solium neurocysticercosis (NCC) are thought to be important factors. Determining whether or not there is infection in the brain is difficult since to be certain, specialized imaging studies, such as CT scans, are required. These are expensive and not widely available. In addition, they are not appropriate for use in large, population-based studies. Thus, blood tests for evidence of infection with T. solium are often done instead to estimate the presence of NCC. In this study's population of persons with epilepsy being seen at a hospital out-patient clinic in South Africa, 37% had CT evidence of NCC, a percentage similar to that reported in other developing countries. The study also found that blood tests were not generally useful compared to CT for correctly identifying those persons who did or did not have NCC, and thus, they cannot be relied upon for field studies of NCC
HCN(1-0) enhancement in the bar of NGC 2903
We have mapped the \hcn emission from two spiral galaxies, NGC2903 and
NGC3504 to study the gas properties in the bars. The HCN(1-0) emission is
detected in the center and along the bar of NGC2903. The line ratio
HCN(1-0)/CO(1-0) ranges from 0.07 to 0.12 with the lowest value in the center.
The enhancement of HCN(1-0) emission along the bar indicates a higher fraction
of dense molecular gas in the bar than at the center. The mass of dense
molecular gas in the center (2.2x 10^7 Msun) is about 6 times lower than that
in the bar (1.2x 10^8 Msun). The total star formation rate (SFR) is estimated
to be 1.4 Msun/yr, where the SFR at the center is 1.9 times higher than that in
the bar. The time scale of consumption of the dense molecular gas in the center
is about 3x 10^7 yr which is much shorter than that in the bar of about 2 to 10
x 10^8 yr. The dynamical time scale of inflow of the gas from the bar to the
center is shorter than the consumption time scale in the bar, which suggests
that the star formation (SF) activity at the center is not deprived of fuel. In
the bar, the fraction of dense molecular gas mass relative to the total
molecular gas mass is twice as high along the leading edge than along the
central axis of the bar. The \hcn emission has a large velocity dispersion in
the bar, which can be attributed partially to the streaming motions indicative
of shocks along the bar. In NGC3504, the HCN(2-0) emission is detected only at
the center. The fraction of dense molecular gas mass in the center is about
15%. Comparison of the SFR with the predictions from numerical simulations
suggest that NGC2903 harbors a young type B bar with a strong inflow of gas
toward the center whereas NGC3504 has an older bar and has already passed the
phase of inflow of gas toward the center.Comment: Acceoted for publication in A&A, 12 figure
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