8 research outputs found

    Estudio sobre la medida del error de planitud con láser interferométrico

    Get PDF
    Las medidas tienen una gran importancia en nuestra vida, ya que las utilizamos desde la estimación a simple vista de una distancia hasta en una investigación compleja. Para realizar medidas de alta precisión o para la puesta a punto de equipos de precisión es necesario un plano de referencia lo más exacto posible, dado por una mesa de planitud. Esta referencia debe ser controlada metrológicamente realizando, por ejemplo, una medida del error de planitud de dicha mesa. Toda medida tiene un grado de variabilidad, y es importante conocerlo. Por ello estudiamos la variabilidad, repetibilidad, reproducibilidad en la medida del error de planitud con el láser interferométrico en varios controles. Por último, hemos estudiado y desarrollado un programa en Excel que realiza los mismos cálculos que el láser interferométrico en el control de planitud, dando claridad y transparencia a los cálculos que realiza el software del láser.Departamento de Ciencias de los Materiales e Ingeniería Metalúrgica, Expresión Gráfica en la Ingeniería, Ingeniería Cartográfica, Geodesia y Fotogrametría, Ingeniería Mecánica e Ingeniería de los Procesos de FabricaciónGrado en Ingeniería Mecánic

    Activating Transcription Factor 4 Modulates TGFβ-Induced Aggressiveness in Triple-Negative Breast Cancer via SMAD2/3/4 and mTORC2 Signaling

    Get PDF
    Purpose: On the basis of the identified stress-independent cellular functions of activating transcription factor 4 (ATF4), we reported enhanced ATF4 levels in MCF10A cells treated with TGFβ1. ATF4 is overexpressed in patients with triple-negative breast cancer (TNBC), but its impact on patient survival and the underlying mechanisms remain unknown. We aimed to determine ATF4 effects on patients with breast cancer survival and TNBC aggressiveness, and the relationships between TGFβ and ATF4. Defining the signaling pathways may help us identify a cell signaling-tailored gene signature.Experimental Design: Patient survival data were determined by Kaplan-Meier analysis. Relationship between TGFβ and ATF4, their effects on aggressiveness (tumor proliferation, metastasis, and stemness), and the underlying pathways were analyzed in three TNBC cell lines and in vivo using patient-derived xenografts (PDX).Results: ATF4 overexpression correlated with TNBC patient survival decrease and a SMAD-dependent crosstalk between ATF4 and TGFβ was identified. ATF4 expression inhibition reduced migration, invasiveness, mammosphere-forming efficiency, proliferation, epithelial-mesenchymal transition, and antiapoptotic and stemness marker levels. In PDX models, ATF4 silencing decreased metastases, tumor growth, and relapse after chemotherapy. ATF4 was shown to be active downstream of SMAD2/3/4 and mTORC2, regulating TGFβ/SMAD and mTOR/RAC1-RHOA pathways independently of stress. We defined an eight-gene signature with prognostic potential, altered in 45% of 2,509 patients with breast cancer.Conclusions: ATF4 may represent a valuable prognostic biomarker and therapeutic target in patients with TNBC, and we identified a cell signaling pathway-based gene signature that may contribute to the development of combinatorial targeted therapies for breast cancer

    Histopathology, microbiology and the inflammatory process associated with Sarcoptes scabiei infection in the Iberian ibex, Capra pyrenaica

    Get PDF
    Background: Sarcoptic mange has been identified as the most significant infectious disease affecting the Iberian ibex (Capra pyrenaica). Despite several studies on the effects of mange on ibex, the pathological and clinical picture derived from sarcoptic mange infestation is still poorly understood. To further knowledge of sarcoptic mange pathology, samples from ibex were evaluated from histological, microbiological and serological perspectives. Methods: Samples of skin, non-dermal tissues and blood were collected from 54 ibex (25 experimentally infected, 15 naturally infected and 14 healthy). Skin biopsies were examined at different stages of the disease for quantitative cellular, structural and vascular changes. Sixteen different non-dermal tissues of each ibex were taken for histological study. Acetylcholinesterase and serum amyloid A protein levels were evaluated from blood samples from ibex with different lesional grade. Samples of mangy skin, suppurative lesions and internal organs were characterized microbiologically by culture. Bacterial colonies were identified by a desorption/ionization time-of-flight mass spectrometry system (MALDI TOF/TOF). Results: The histological study of the skin lesions revealed serious acanthosis, hyperkeratosis, rete ridges, spongiotic oedema, serocellular and eosinophilic crusts, exocytosis foci, apoptotic cells and sebaceous gland hyperplasia. The cellular response in the dermis was consistent with type I and type IV hypersensitivity responses. The most prominent histological findings in non-dermal tissues were lymphoid hyperplasia, leukocytosis, congestion and the presence of amyloid deposits. The increase in serum concentrations of acetylcholinesterase and amyloid A protein correlated positively with the establishment of the inflammatory response in mangy skin and the presence of systemic amyloidosis. A wide variety of bacterial agents were isolated and the simultaneous presence of these in mangy skin, lymph nodes and internal organs such as lungs, liver, spleen and kidney was compatible with a septicaemic pattern of infection. Conclusions: The alteration of biomarkers of inflammation and its implication in the pathogenesis of the disease and development of lesions in non-dermal tissues and septicaemic processes are serious conditioners for the survival of the mangy ibex. This severe clinical picture could be an important factor when considering the decision to eliminate animals that exceed a certain disease threshold from a populationPeer reviewe

    Evidence for the Effect of Vaccination on Host-Pathogen Interactions in a Murine Model of Pulmonary Tuberculosis by .

    No full text
    The global control of Tuberculosis remains elusive, and Bacillus Calmette-Guérin (BCG) -the most widely used vaccine in history-has proven insufficient for reversing this epidemic. Several authors have suggested that the mass presence of vaccinated hosts might have affected the Mycobacterium tuberculosis (MTB) population structure, and this could in turn be reflected in a prevalence of strains with higher ability to circumvent BCG-induced immunity, such as the recent Beijing genotype. The effect of vaccination on vaccine-escape variants has been well-documented in several bacterial pathogens; however the effect of the interaction between MTB strains and vaccinated hosts has never been previously described. In this study we show for the first time the interaction between MTB Beijing-genotype strains and BCG-vaccinated hosts. Using a well-controlled murine model of progressive pulmonary tuberculosis, we vaccinated BALB/c mice with two different sub-strains of BCG (BCG-Phipps and BCG-Vietnam). Following vaccination, the mice were infected with either one of three selected MTB strains. Strains were selected based on lineage, and included two Beijing-family clinical isolates (strains 46 and 48) and a well-characterized laboratory strain (H37Rv). Two months after infection, mice were euthanized and the bacteria extracted from their lungs. We characterized the genomic composite of the bacteria before and after exposure to vaccinated hosts, and also characterized the local response to the bacteria by sequencing the lung transcriptome in animals during the infection. Results from this study show that the interaction within the lungs of the vaccinated hosts results in the selection of higher-virulence bacteria, specifically for the Beijing genotype strains 46 and 48. After exposure to the BCG-induced immune response, strains 46 and 48 acquire genomic mutations associated with several virulence factors. As a result, the bacteria collected from these vaccinated hosts have an increased ability for immune evasion, as shown in both the host transcriptome and the histopathology studies, and replicates far more efficiently compared to bacteria collected from unvaccinated hosts or to the original-stock strain. Further research is warranted to ascertain the pathways associated with the genomic alterations. However, our results highlight novel host-pathogen interactions induced by exposure of MTB to BCG vaccinated hosts
    corecore