Mitoxantrone Shows In Vitro, but Not In Vivo Antiviral Activity against Human Respiratory Syncytial Virus

Human respiratory syncytial virus (HRSV) is the most common cause of severe respiratory infections in infants and young children, often leading to hospitalization. In addition, this virus poses a serious health risk in immunocompromised individuals and the elderly. HRSV is also a major nosocomial hazard in healthcare service units for patients of all ages. Therefore, the development of antiviral treatments against HRSV is a global health priority. In this study, mitoxantrone, a synthetic anthraquinone with previously reported in vitro antiprotozoal and antiviral activities, inhibits HRSV replication in vitro, but not in vivo in a mice model. These results have implications for preclinical studies of some drug candidates.This work was supported by the Spanish Ministry of Science and Innovation SAF2014-58052 and “Acción Estratégica en Salud” MPY 388/18 to D.L.S

Acid Stripping after Infection Improves the Detection of Viral HLA Class I Natural Ligands Identified by Mass Spectrometry

Identification of a natural human leukocyte antigen (HLA) ligandome is a key element to understand the cellular immune response. Advanced high throughput mass spectrometry analyses identify a relevant, but not complete, fraction of the many tens of thousands of self-peptides generated by antigen processing in live cells. In infected cells, in addition to this complex HLA ligandome, a minority of peptides from degradation of the few proteins encoded by the viral genome are also bound to HLA class I molecules. In this study, the standard immunopeptidomics strategy was modified to include the classical acid stripping treatment after virus infection to enrich the HLA ligandome in virus ligands. Complexes of HLA-B*27:05-bound peptide pools were isolated from vaccinia virus (VACV)-infected cells treated with acid stripping after virus infection. The HLA class I ligandome was identified using high throughput mass spectrometry analyses, yielding 37 and 51 natural peptides processed and presented untreated and after acid stripping treatment VACV-infected human cells, respectively. Most of these virus ligands were identified in both conditions, but exclusive VACV ligands detected by mass spectrometry detected on acid stripping treatment doubled the number of those identified in the untreated VACV-infected condition. Theoretical binding affinity prediction of the VACV HLA-B*27:05 ligands and acute antiviral T cell response characterization in the HLA transgenic mice model showed no differences between HLA ligands identified under the two conditions: untreated and under acid stripping condition. These findings indicated that acid stripping treatment could be useful to identify HLA class I ligands from virus-infected cells.This work was supported by the Spanish Ministry of Science and Innovation SAF2014-58052 and “Acción Estratégica en Salud” MPY 388/18 to D.L.S

3D reconstruction of syn-tectonic strata deposited during the inversion of salt-related structures : insights from the Llert syncline (South-central Pyrenees)

The Llert syncline is located in the South-central Pyrenees, between the eastern termination of the EW-trending Cotiella Basin and the north-western limb of the NS-trending Turbón-Serrado fold system. The Cotiella Basin is an inverted upper Coniacian-lower Santonian salt-floored post-rift extensional basin developed along the northern Iberian rift system. The Turbón-Serrado fold system consists of upper Santonian - Maastrichtian contractional salt-cored anticlines developed along an inverted transfer zone of the Pyrenean rift system. Based on field research, this paper presents a 3D reconstruction of the Llert syncline in order to further constrain the transition between these oblique salt-related structures. Our results suggest that the evolution of the Llert syncline was mainly controlled by tectonic shortening related to the tectonic inversion of the Cotiella Basin synchronously to the growth of the Turbón-Serrado detachment anticline, and by the pre-compressional structural framework of the Pyrenean rift system. Our contribution provides new insight into the geometric and kinematic relationships of structures developed during the inversion of passive margins involving salt

Efectividad y seguridad de los bisfosfonatos en el tratamiento de la osteoporosis infantil secundaria

Bisfosfonatos; Efectividad; NiñoBisfosfonats; Efectivitat; NenBisphosphonates; Effectiveness; ChildIntroduction There are few studies on effectiveness and safety of bisphosphonate therapy in secondary osteoporosis in children. The aim of this research was to analyse effectiveness and safety of bisphosphonates in secondary osteoporosis in children. Patients and methods Multicentre retrospective study in patients younger than 18 suffering from secondary osteoporosis and who have received bisphosphonates. Clinical data were recorded. Bone mineral density (BMD) was assessed in terms of BMD Z-score in lumbar spine (ZBMDls) measured by dual-energy X-ray absorptiometry (DXA). Effectiveness was valued at changes in ZBMDls one and two years after the onset of bisphosphonates and at the decrese in the number of fractures a year. Adverse events reported were recorded. Descriptive and bivariant analysis was performed. Results 32 patients were recruited. ZBMDls increased one year after the onset of treatment ((−2.46 ± 0.96) vs. (−1.54 ± 1.38); p < .001). Fractures a year dicreased significantly (1 (1–2) vs. 0 (0–0.61); p < .001). ZBMDls increase was higher in patients who were able to walk (1.88 ± 0.72 vs. 0.55 ± 0.82; p = .07) and correlated positively with body mass index (BMI)- for- age percentile (rho: 0.564; p < .001). The decrease in the number of fractures a year was higher in patients with lower initial fracture rate (rho: −0,47; p = .006) and with higher initial ZBMDls (rho: −0.47; p = .07). 10 adverse events were reported in 7 patients (22%), all of them intravenous bisphosphonates related. No association was found between adverse events and studied variables. Conclusions Bisphosphonates are effective in secondary osteoporosis in children. Response seems to be better in patients who are able to walk, well-nourished and in the early stages of the disease. Adverse events were frequent but mild.Introducción Los estudios sobre efectividad y seguridad de los bisfosfonatos en osteoporosis infantil secundaria (OIS) son escasos. El objetivo fue analizar efectividad y seguridad de los bisfosfonatos en OIS. Pacientes y métodos Estudio multicéntrico retrospectivo en <18 años afectos de OIS tratados con bisfosfonatos. Se recogieron variables clínicas. Se valoró densidad mineral ósea (DMO) mediante el Z-score de DMO en columna lumbar (ZDMOcl) medido por absorciometría de rayos X de doble energía (DXA). Valoramos efectividad en función del cambio del ZDMOcl al año y a los dos años de su inicio y del descenso del número de fracturas/año. Los eventos adversos reportados fueron recogidos. Se realizó análisis descriptivo y bivariante. Resultados Se reclutaron 32 pacientes. El ZDMOcl se incrementó al año del inicio del tratamiento ((−2,46 ± 0,96) vs. (−1,54 ± 1,38); p < 0,001). El número de fracturas/año disminuyó significativamente (1 (1–2) vs. 0 (0–0,61); p < 0,001). El cambio en el ZDMOcl fue mayor en los pacientes deambulantes (1,88 ± 0,72 vs. 0,55 ± 0,82; p = 0,07) y se correlacionó positivamente con el percentil del IMC (rho: 0,564; p < 0,001). El descenso del número de fracturas/año fue mayor en los pacientes con menor tasa inicial de fracturas (rho: −0,47; p = 0,006) y cuanto mayor era el Z-score inicial (rho: −0,47; p = 0,07). Se reportaron 10 eventos adversos leves en 7 pacientes (22%), todos con bisfosfonatos intravenosos. No se halló relación entre eventos adversos y las variables estudiadas. Conclusiones Los bisfosfonatos son efectivos en OIS. La respuesta parece ser mejor en pacientes deambulantes, bien nutridos y en estadios precoces de la enfermedad. Resultan seguros, siendo los efectos adversos leves, aunque frecuentes

Macrofauna and biostratigraphy of the Rollrock Section, northern Ellesmere Island, Canadian Arctic Islands - a comprehensive high latitude archive of the Jurassic - Cretaceous Transition

Working in the Arctic would not be possible without manifold support. Our sincere thanks go to the following people in Canada who helped to make our research a success: Sylvie LeBlanc (Department of Culture and Heritage, Iglooik, Canada); Jane Chisholm (Parks Canada, Iqaluit, Canada); John Innis (Universal Helicopters); the rangers of Parks Canada at Quttinirpaaq National Park (Ellesmere Island, Canada); the Polar Continental Shelf Programme team at Resolute (Cornwallis Island, Canada); Margaret Currie, Laura Smyk and Kieran Sheperd (all Canadian Museum of Nature, Ottawa, Canada). Alex Chavanne (California, USA) joined our team as an excellent field assistant, helped logging and sampling the Rollrock Section and found the giant Dorsoplanites specimen. Sarah Wallace-Jones (Sedgwick Museum, Department of Earth Sciences, University of Cambridge, UK) provided access to preparation labs. Magdalena Biszczuk (CASP) prepared the maps in Fig. 1; and Michael Pointon (CASP) polished the English. Ashton F. Embry (Geological Survey of Canada, Calgary) kindly shared his field observations and analytical results on the Rollrock Section. Mikhail Rogov (Geologicheskij Institut, Rossijskaja Akademija Nauk, Moscow) greatly helped by sharing expert knowledge regarding ammonites of the Jurassic-Cretaceous boundary interval and by providing literature. CASP's industry sponsors are acknowledged for funding the Canadian Arctic Islands Project. Peter Alsen (Geological Survey of Denmark and Greenland, Copenhagen, Denmark) and Terence Poulton (Natural Resources Canada, Calgary, Canada) provided careful and detailed reviews, which greatly improved the manuscript.Peer reviewedPostprin

Alterations in the abundance and co-occurrence of Akkermansia muciniphila and Faecalibacterium prausnitzii in the colonic mucosa of inflammatory bowel disease subjects

This work was funded by the Universitat de Girona projects MPCUdG2016-009 and GdRCompetUdG2017, and the Spanish Ministry of Education and Science through projects SAF2006-00414, SAF2010-15896 and SAF2013-43284-P, being the last co-funded by the European Regional Development. Dr. Sylvia H. Duncan acknowledges support from the Scottish Government Research and Environment Science and Analytical Services Division (RESAS).Peer reviewedPublisher PD

FungalBraid: A GoldenBraid-based modular cloning platform for the assembly and exchange of DNA elements tailored to fungal synthetic biology

[EN] Current challenges in the study and biotechnological exploitation of filamentous fungi are the optimization of DNA cloning and fungal genetic transformation beyond model fungi, the open exchange of ready-to-use and standardized genetic elements among the research community, and the availability of universal synthetic biology tools and rules. The GoldenBraid (GB) cloning framework is a Golden Gate-based DNA cloning system developed for plant synthetic biology through Agrobacterium tumefaciens-mediated genetic transformation (ATMT). In this study, we develop reagents for the adaptation of GB version 3.0 from plants to filamentous fungi through: (i) the expansion of the GB toolbox with the domestication of fungal-specific genetic elements; (ii) the design of fungal-specific GB structures; and (iii) the ATMT and gene disruption of the plant pathogen Penicillium digitatum as a proof of concept. Genetic elements domesticated into the GB entry vector pUPD2 include promoters, positive and negative selection markers and terminators. Interestingly, some GB elements can be directly exchanged between plants and fungi, as demonstrated with the marker hph for Hyg(R) or the fluorescent protein reporter YFP. The iterative modular assembly of elements generates an endless number of diverse transcriptional units and other higher order combinations in the pDGB3 alpha/pDGB3 Omega destination vectors. Furthermore, the original plant GB syntax was adapted here to incorporate specific GB structures for gene disruption through homologous recombination and dual selection. We therefore have successfully adapted the GB technology for the ATMT of fungi. We propose the name of FungalBraid (FB) for this new branch of the GB technology that provides open, exchangeable and collaborative resources to the fungal research community.This work was funded by grants BIO2015-68790-C2-1-R and BIO2016-78601-R from the "Ministerio de Economia y Competitividad" (MINECO, Spain). SG was recipient of a predoctoral scholarship (FPU13/04584) within the FPU program from "Ministerio de Educacion, Cultura y Deporte" (MECD, Spain). We acknowledge the excellent technical assistance of Tania Campos and the help in the microscopy experiments of Jose M. Coll-Marques (IATA, Valencia, Spain). We also thank Dr. Pilar Moya (Universitat Politecnica de Valencia, Spain) for helpful discussions during the initial stages of this project.Hernanz-Koers, M.; Gandía-Gómez, M.; Garrigues-Cubells, SM.; Manzanares-Mir, PM.; Yenush, L.; Orzáez Calatayud, DV.; Marcos -Lopez, JF. (2018). FungalBraid: A GoldenBraid-based modular cloning platform for the assembly and exchange of DNA elements tailored to fungal synthetic biology. Fungal Genetics and Biology. 116:51-61. https://doi.org/10.1016/j.fgb.2018.04.010S516111

Evaluation of bacterial biomarkers to aid in challenging inflammatory bowel diseases diagnostics and subtype classification

Supported by the Spanish Ministry of Education and Science, No. SAF2010-15896, No. SAF2013-43284-P and No. SAF2017-82261-P.Peer reviewedPostprintPublisher PD

Nonstoichiometry driven ferromagnetism in double perovskite La2Ni1-xMn1+ xO6 insulating thin films

This is an open access article published under an ACS AuthorChoice License. See Standard ACS AuthorChoice/Editors' Choice Usage AgreementIn this work we report on the epitaxial growth of LaNiMnO double perovskite thin films on top of (001) oriented SrTiO substrates by RF magnetron sputtering. The influence of oxygen pressure (P O) and growth temperature on the microstructure, stoichiometry of the films, and magnetic and transport properties is thoroughly investigated. It is found that high oxygen pressure promotes the growth of stoichiometric films, with a Ni/Mn ratio almost equal to 1. However, these films exhibit poor ferromagnetic properties with respect to the expected optimum values corresponding to ferromagnetic ordering mediated by superexchange interaction between Mn and Ni according to the Goodenough-Kanamori rules. Most interestingly, films grown at low P O exhibit Ni/Mn ratios below 1, but ferromagnetic properties close to the optimal ones. The valence balance between Ni and Mn ions in nonstoichiometric sample has been elucidated by X-ray absorption spectroscopy. The results indicate that Ni deficiency plays a crucial role in the puzzling insulating ferromagnetic behavior observed in nonstoichiometric samples

Particle separation by horizontal deflection in paramagnetic fluid

This paper describes the horizontal deflection behaviour of the streams of particles in paramagnetic fluids under a high-gradient superconducting magnetic field, which is the continued work on the exploration of particle magneto-Archimedes levitation. Based on the previous work on the horizontal deflection of a single particle, a glass box and collector had been designed to observe the movement of particle group in paramagnetic fluids. To get the exact separation efficiency, the method of "sink-float" involved the high density fluid polytungstate (dense medium separation) and MLA (Mineral Liberation Analyser) was performed. It was found that the particles were deflected and settled at certain positions on the container floor due to the combined forces of gravity and magneto-Archimedes forces as well as a lateral buoyancy (displacement) force. Mineral particles with different densities and susceptibilities could be deflected to different positions, thus producing groups of similar types of particles. The work described here, although in its infancy, could form the basis of new approach of separating particles based on a combination of susceptibility and density