1,073 research outputs found
ISG15 Is Upregulated in Respiratory Syncytial Virus Infection and Reduces Virus Growth through Protein ISGylation
UNLABELLED: Human respiratory syncytial virus (RSV), for which neither a vaccine nor an effective therapeutic treatment is currently available, is the leading cause of severe lower respiratory tract infections in children. Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein that is highly increased during viral infections and has been reported to have an antiviral or a proviral activity, depending on the virus. Previous studies from our laboratory demonstrated strong ISG15 upregulation during RSV infection in vitro. In this study, an in-depth analysis of the role of ISG15 in RSV infection is presented. ISG15 overexpression and small interfering RNA (siRNA)-silencing experiments, along with ISG15 knockout (ISG15(-/-)) cells, revealed an anti-RSV effect of the molecule. Conjugation inhibition assays demonstrated that ISG15 exerts its antiviral activity via protein ISGylation. This antiviral activity requires high levels of ISG15 to be present in the cells before RSV infection. Finally, ISG15 is also upregulated in human respiratory pseudostratified epithelia and in nasopharyngeal washes from infants infected with RSV, pointing to a possible antiviral role of the molecule in vivo. These results advance our understanding of the innate immune response elicited by RSV and open new possibilities to control infections by the virus. IMPORTANCE: At present, no vaccine or effective treatment for human respiratory syncytial virus (RSV) is available. This study shows that interferon-stimulated gene 15 (ISG15) lowers RSV growth through protein ISGylation. In addition, ISG15 accumulation highly correlates with the RSV load in nasopharyngeal washes from children, indicating that ISG15 may also have an antiviral role in vivo. These results improve our understanding of the innate immune response to RSV and identify ISG15 as a potential target for virus control.This work was supported by grant PI11/00590 from Fondo de Investigación Sanitaria to I.M.S
Urea-based fertilization strategies to reduce yield-scaled N oxides and enhance bread-making quality in a rainfed Mediterranean wheat crop
Acciones de acogida del proyecto mentor de la EUITI
Desde el curso académico 2008/2009 el Proyecto Mentor de la Escuela Universitaria de Ingeniería Técnica Industrial (EUITI) de la UPM [1] participa en distintas acciones de acogida de los alumnos de nuevo ingreso propio del centro. Estas actividades son el primer contacto de los mentores con los alumnos de nuevo ingreso y además son reforzadas por el apoyo y experiencia de los tutores y mentores del curso anterior, favoreciendo la interrelación de alumnos de distintos cursos y especialidades. Para la correcta realización de estas actividades, los alumnos mentores reciben un intensivo programa de formación que incluye aspectos psicosociales propios de la mentoría [2]. La presente comunicación tiene el propósito de describir dichas acciones así como presentar y valorar los resultados obtenidos a través de la encuest
Performance of Magnetic-Superconductor Non-Contact Harmonic Drive for Cryogenic Space Applications
Harmonic drives are profusely used in aerospace mainly because of their compactness and large reduction ratio. However, their use in cryogenic environments is still a challenge. Lubrication and fatigue are non-trivial issues under these conditions. The objective of the Magnetic-Superconductor Cryogenic Non-contact Harmonic Drive (MAGDRIVE) project, funded by the EU Space FP7, is to design, build, and test a new concept of MAGDRIVE. Non-contact interactions among magnets, soft magnetic materials, and superconductors are efficiently used to provide a high reduction ratio gear that smoothly and naturally operates at cryogenic environments. The limiting elements of conventional harmonic drives (teeth, flexspline, and ball bearings) are substituted by contactless mechanical components (magnetic gear and superconducting magnetic bearings). The absence of contact between moving parts prevents wear, lubricants are no longer required, and the operational lifetime is greatly increased. This is the first mechanical reducer in mechanical engineering history without any contact between moving parts. In this paper, the test results of a −1:20 inverse reduction ratio MAGDRIVE prototype are reported. In these tests, successful operation at 40 K and 10−3 Pa was demonstrated for more than 1.5 million input cycles. A maximum torque of 3 N·m and an efficiency of 80% were demonstrated. The maximum tested input speed was 3000 rpm, six times the previous existing record for harmonic drives at cryogenic temperature
High-resolution hepatitis C virus subtyping using NS5B deep sequencing and phylogeny, an alternative to current methods
HepatitisCvirus(HCV)is classified into seven major genotypesand67 subtypes. Recent studies haveshownthat inHCVgenotype 1-infected
patients, response rates to regimens containingdirect-acting antivirals(DAAs)are subtype dependent. Currently available genotypingmethods
have limited subtyping accuracy.Wehave evaluated theperformanceof adeep-sequencing-basedHCVsubtyping assay, developed for the
454/GS-Junior platform, in comparisonwith thoseof two commercial assays (VersantHCVgenotype 2.0andAbbott Real-timeHCVGenotype
II)andusingdirectNS5Bsequencing as a gold standard (direct sequencing), in 114 clinical specimenspreviously tested by first-generation
hybridization assay (82 genotype 1and32 with uninterpretable results). Phylogenetic analysis of deep-sequencing reads matched subtype
1 callingbypopulation Sanger sequencing(69%1b,31%1a) in 81 specimensandidentified amixed-subtype infection (1b/3a/1a) in one sample.
Similarly,amongthe 32previously indeterminate specimens, identical genotypeandsubtype results were obtained by directanddeep
sequencing in all but four samples with dual infection. In contrast, both VersantHCVGenotype 2.0andAbbott Real-timeHCVGenotype II
failed subtype 1 calling in 13 (16%) samples eachandwere unable to identify theHCVgenotype and/or subtype inmore than half of the nongenotype
1 samples.Weconcluded that deep sequencing ismore efficient forHCVsubtyping than currently available methodsandallows
qualitative identificationofmixed infectionsandmay bemorehelpfulwith respect to informing treatment strategies withnewDAA-containing
regimens across allHCVsubtypesThis study has been supported by CDTI (Centro para el Desarrollo Tecnológico
Industrial), Spanish Ministry of Economics and Competitiveness
(MINECO), IDI-20110115; MINECO projects SAF 2009-10403; and
also by the Spanish Ministry of Health, Instituto de Salud Carlos III (FIS)
projects PI10/01505, PI12/01893, and PI13/00456. CIBERehd is funded
by the Instituto de Salud Carlos III, Madrid, Spain. Work at CBMSO was
supported by grant MINECO-BFU2011-23604, FIPSE, and Fundación
Ramón Areces.
X. Forns received unrestricted grant support from Roche and has
acted as advisor for MSD, Gilead, and Abbvie. M. Alvarez-Tejado, J. Gregori,
and J. M. Muñoz work in Roche Diagnostic
Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication
International audienceno abstrac
The genetic ancestry of American Creole cattle inferred from uniparental and autosomal genetic markers
Cattle imported from the Iberian Peninsula spread throughout America in the early years of discovery and colonization to originate Creole breeds, which adapted to a wide diversity of environments and later received influences from other origins, including zebu cattle in more recent years. We analyzed uniparental genetic markers and autosomal microsatellites in DNA samples from 114 cattle breeds distributed worldwide, including 40 Creole breeds representing the whole American continent, and samples from the Iberian Peninsula, British islands, Continental Europe, Africa and American zebu. We show that Creole breeds differ considerably from each other, and most have their own identity or group with others from neighboring regions. Results with mtDNA indicate that T1c-lineages are rare in Iberia but common in Africa and are well represented in Creoles from Brazil and Colombia, lending support to a direct African influence on Creoles. This is reinforced by the sharing of a unique Y-haplotype between cattle from Mozambique and Creoles from Argentina. Autosomal microsatellites indicate that Creoles occupy an intermediate position between African and European breeds, and some Creoles show a clear Iberian signature. Our results confirm the mixed ancestry of American Creole cattle and the role that African cattle have played in their development
CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative
Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research
The genetic ancestry of american creole cattle inferred from uniparental and autosomal genetic markers.
Cattle imported from the Iberian Peninsula spread throughout America in the early years of discovery and colonization to originate Creole breeds, which adapted to a wide diversity of environments and later received influences from other origins, including zebu cattle in more recent years. We analyzed uniparental genetic markers and autosomal microsatellites in DNA samples from 114 cattle breeds distributed worldwide, including 40 Creole breeds representing the whole American continent, and samples from the Iberian Peninsula, British islands, Continental Europe, Africa and American zebu. We show that Creole breeds differ considerably from each other, and most have their own identity or group with others from neighboring regions. Results with mtDNA indicate that T1c-lineages are rare in Iberia but common in Africa and are well represented in Creoles from Brazil and Colombia, lending support to a direct African influence on Creoles. This is reinforced by the sharing of a unique Y-haplotype between cattle from Mozambique and Creoles from Argentina. Autosomal microsatellites indicate that Creoles occupy an intermediate position between African and European breeds, and some Creoles show a clear Iberian signature. Our results confirm the mixed ancestry of American Creole cattle and the role that African cattle have played in their development
Mitochondrial physiology
As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery
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