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1.
Ana Giner Lóránt Lakatos Meritxell García-Chapa Juan José López-Moya József Burgyán 《PLoS pathogens》2010,6(7)
RNA silencing is an evolutionarily conserved sequence-specific gene-inactivation system that also functions as an antiviral mechanism in higher plants and insects. To overcome antiviral RNA silencing, viruses express silencing-suppressor proteins. These viral proteins can target one or more key points in the silencing machinery. Here we show that in Sweet potato mild mottle virus (SPMMV, type member of the Ipomovirus genus, family Potyviridae), the role of silencing suppressor is played by the P1 protein (the largest serine protease among all known potyvirids) despite the presence in its genome of an HC-Pro protein, which, in potyviruses, acts as the suppressor. Using in vivo studies we have demonstrated that SPMMV P1 inhibits si/miRNA-programmed RISC activity. Inhibition of RISC activity occurs by binding P1 to mature high molecular weight RISC, as we have shown by immunoprecipitation. Our results revealed that P1 targets Argonaute1 (AGO1), the catalytic unit of RISC, and that suppressor/binding activities are localized at the N-terminal half of P1. In this region three WG/GW motifs were found resembling the AGO-binding linear peptide motif conserved in metazoans and plants. Site-directed mutagenesis proved that these three motifs are absolutely required for both binding and suppression of AGO1 function. In contrast to other viral silencing suppressors analyzed so far P1 inhibits both existing and de novo formed AGO1 containing RISC complexes. Thus P1 represents a novel RNA silencing suppressor mechanism. The discovery of the molecular bases of P1 mediated silencing suppression may help to get better insight into the function and assembly of the poorly explored multiprotein containing RISC. 相似文献
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Manuel Algara Meritxell Arenas Dolores De las Peñas Eloisa Bayo Julia Muñoz José Antonio Carceller Juan Salinas Ferran Moreno Francisco Martínez Ezequiel González Ángel Montero 《Reports of Practical Oncology and Radiotherapy》2012,17(3):122-128
AimTo evaluate the resources and techniques used in the irradiation of patients with breast cancer after lumpectomy or mastectomy and the status of implementation of new techniques and therapeutic schedules in our country.BackgroundThe demand for cancer care has increased among the Spanish population, as long as cancer treatment innovations have proliferated. Radiation therapy in breast cancer has evolved exponentially in recent years with the implementation of three-dimensional conformal radiotherapy, intensity modulated radiotherapy, image guided radiotherapy and hypofractionation.Material and MethodsAn original survey questionnaire was sent to institutions participating in the SEOR-Mama group (GEORM). In total, the standards of practice in 969 patients with breast cancer after surgery were evaluated.ResultsThe response rate was 70% (28/40 centers). In 98.5% of cases 3D conformal treatment was used. All the institutions employed CT-based planning treatment. Boost was performed in 56.4% of patients: electrons in 59.8%, photons in 23.7% and HDR brachytherapy in 8.8%. Fractionation was standard in 93.1% of patients. Supine position was the most frequent. Only 3 centers used prone position. The common organs of risk delimited were: homolateral lung (80.8%) and heart (80.8%). In 84% histograms were used. An 80.8% of the centers used isocentric technique. In 62.5% asymmetric fields were employed. CTV was delimited in 46.2%, PTV in 65% and both in 38.5%. A 65% of the centers checked with portal films. IMRT and hypofractionation were used in 1% and in 5.5% respectively.ConclusionIn most of centers, 3D conformal treatment and CT-based planning treatment were used. IMRT and hypofractionation are currently poorly implemented in Spain. 相似文献
3.
Jovani Catalán-Dibene Suzanne M. Johnson Ricardo Eaton Adriana L. Romero-Olivares Raúl C. Baptista-Rosas Demosthenes Pappagianis Meritxell Riquelme 《Fungal biology》2014,118(3):330-339
Coccidioidomycosis (Valley Fever) represents a serious threat to inhabitants of endemic areas of North America. Despite successful clinical isolations of the fungal etiological agent, Coccidioides spp., the screening of environmental samples has had low effectiveness, mainly because of the poor characterization of Coccidioides ecological niche. We explored Valle de las Palmas, Baja California, Mexico, a highly endemic area near the U.S.–Mexico border, where we previously detected Coccidioides via culture-independent molecular methods. By testing the serum from 40-trapped rodents with ELISA, we detected antibodies against Coccidioides in two species: Peromyscus maniculatus and Neotoma lepida. This study comprises the first report of wild rodent serum tested for coccidioidal antibodies, and sets the basis to analyze this pathogen in its natural environment and explore its potential ecological niche. 相似文献
4.
Jos C. E. Serrano Juan Antonio Baena‐Fustegueras Meritxell Martin‐Gari Helene Rassendren Anna Cassanye Alba Naudí Carolina Lpez‐Cano Enric Snchez María Cruz de la Fuente‐Jurez Fernando Herrerías Gonzlez Jorge J. Olsina Kissler Albert Lecube Manuel Portero‐Otín 《Obesity (Silver Spring, Md.)》2019,27(7):1133-1140
5.
Lorena Pantano Meritxell Jodar Mads Bak Josep Lluís Ballescà Niels Tommerup Rafael Oliva Tanya Vavouri 《RNA (New York, N.Y.)》2015,21(6):1085-1095
At the end of mammalian sperm development, sperm cells expel most of their cytoplasm and dispose of the majority of their RNA. Yet, hundreds of RNA molecules remain in mature sperm. The biological significance of the vast majority of these molecules is unclear. To better understand the processes that generate sperm small RNAs and what roles they may have, we sequenced and characterized the small RNA content of sperm samples from two human fertile individuals. We detected 182 microRNAs, some of which are highly abundant. The most abundant microRNA in sperm is miR-1246 with predicted targets among sperm-specific genes. The most abundant class of small noncoding RNAs in sperm are PIWI-interacting RNAs (piRNAs). Surprisingly, we found that human sperm cells contain piRNAs processed from pseudogenes. Clusters of piRNAs from human testes contain pseudogenes transcribed in the antisense strand and processed into small RNAs. Several human protein-coding genes contain antisense predicted targets of pseudogene-derived piRNAs in the male germline and these piRNAs are still found in mature sperm. Our study provides the most extensive data set and annotation of human sperm small RNAs to date and is a resource for further functional studies on the roles of sperm small RNAs. In addition, we propose that some of the pseudogene-derived human piRNAs may regulate expression of their parent gene in the male germline. 相似文献
6.
Oliver Fuerst Yibin Lin Meritxell Granell Gérard Leblanc Esteve Padrós Víctor A. Lórenz-Fonfría Josep Cladera 《The Journal of biological chemistry》2015,290(26):16261-16271
We examine the role of Lys-377, the only charged residue in helix XI, on the functional mechanism of the Na+-sugar melibiose symporter from Escherichia coli. Intrinsic fluorescence, FRET, and Fourier transform infrared difference spectroscopy reveal that replacement of Lys-377 with either Cys, Val, Arg, or Asp disables both Na+ and melibiose binding. On the other hand, molecular dynamics simulations extending up to 200–330 ns reveal that Lys-377 (helix XI) interacts with the anionic side chains of two of the three putative ligands for cation binding (Asp-55 and Asp-59 in helix II). When Asp-59 is protonated during the simulations, Lys-377 preferentially interacts with Asp-55. Interestingly, when a Na+ ion is positioned in the Asp-55-Asp-59 environment, Asp-124 in helix IV (a residue essential for melibiose binding) reorients and approximates the Asp-55-Asp-59 pair, and all three acidic side chains act as Na+ ligands. Under these conditions, the side chain of Lys-377 interacts with the carboxylic moiety of these three Asp residues. These data highlight the crucial role of the Lys-377 residue in the spatial organization of the Na+ binding site. Finally, the analysis of the second-site revertants of K377C reveals that mutation of Ile-22 (in helix I) preserves Na+ binding, whereas that of melibiose is largely abolished according to spectroscopic measurements. This amino acid is located in the border of the sugar-binding site and might participate in sugar binding through apolar interactions. 相似文献
7.
Simon Borna Ales Drobek Jarmila Kralova Daniela Glatzova Iva Splichalova Matej Fabisik Jana Pokorna Tereza Skopcova Pavla Angelisova Veronika Kanderova Julia Starkova Petr Stanek Orest V. Matveichuk Nataliia Pavliuchenko Katarzyna Kwiatkowska Majd B. Protty Michael G. Tomlinson Meritxell Alberich‐Jorda Vladimir Korinek Tomas Brdicka 《Journal of cellular and molecular medicine》2020,24(2):1980-1992
WW domain binding protein 1‐like (WBP1L), also known as outcome predictor of acute leukaemia 1 (OPAL1), is a transmembrane adaptor protein, expression of which correlates with ETV6‐RUNX1 (t(12;21)(p13;q22)) translocation and favourable prognosis in childhood leukaemia. It has a broad expression pattern in haematopoietic and in non‐haematopoietic cells. However, its physiological function has been unknown. Here, we show that WBP1L negatively regulates signalling through a critical chemokine receptor CXCR4 in multiple leucocyte subsets and cell lines. We also show that WBP1L interacts with NEDD4‐family ubiquitin ligases and regulates CXCR4 ubiquitination and expression. Moreover, analysis of Wbp1l‐deficient mice revealed alterations in B cell development and enhanced efficiency of bone marrow cell transplantation. Collectively, our data show that WBP1L is a novel regulator of CXCR4 signalling and haematopoiesis. 相似文献
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Myotonic dystrophy 1 (MD1) is caused by a CTG expansion in the 3′-unstranslated region of the myotonic dystrophy protein kinase (DMPK) gene. MD1 patients frequently present insulin resistance and increased visceral adiposity. We examined whether DMPK deficiency is a genetic risk factor for high-fat diet-induced adiposity and insulin resistance using the DMPK knockout mouse model. We found that high-fat fed DMPK knockout mice had significantly increased body weights, hypertrophic adipocytes and whole-body insulin resistance compared with wild-type mice. This nutrient-genome interaction should be considered by physicians given the cardiometabolic risks and sedentary lifestyle associated with MD1 patients. 相似文献
10.
Meritxell Gironella Cedric Malicet Carla Cano Maria José Sandi Tewfik Hamidi Ricardo Martin Neme Tauil Mariela Baston Pia Valaco Silvia Moreno Frederic Lopez Jose Luis Neira Jean Charles Dagorn Juan Lucio Iovanna 《Journal of cellular physiology》2009,221(3):594-602
The stress protein p8 is a small, highly basic, unfolded, and multifunctional protein. We have previously shown that most of its functions are exerted through interactions with other proteins, whose activities are thereby enhanced or repressed. In this work we describe another example of such mechanism, by which p8 binds and negatively regulates MSL1, a histone acetyl transferase (HAT)‐associated protein, which in turn binds the DNA‐damage‐associated 53BP1 protein to facilitate DNA repair following DNA γ‐irradiation. Contrary to the HAT‐associated activity, MSL1‐dependent DNA‐repair activity is almost completely dependent on 53BP1 expression. The picture that has emerged from our findings is that 53BP1 could be a scaffold that gets the HAT MSL1‐dependent DNA‐repair activity to the sites of DNA damage. Finally, we also found that, although p8 expression is transiently activated after γ‐irradiation, it is eventually submitted to sustained down‐regulation, presumably to allow development of MSL1‐associated DNA‐repair activity. We conclude that interaction of MSL1 with 53BP1 brings MSL1‐dependent HAT activity to the vicinity of damaged DNA. MSL1‐dependent HAT activity, which is negatively regulated by the stress protein p8, induces chromatin remodeling and relaxation allowing access to DNA of the repair machinery. J. Cell. Physiol. 221: 594–602, 2009. © 2009 Wiley‐Liss, Inc. 相似文献