Nc886 is a 102 bp non-coding RNA transcript initially classified as a microRNA precursor (Pre-miR-886), later as a divergent homologue of the vault RNAs (vtRNA 2-1) and more recently as a novel type ...of RNA (nc886). Although nc886/vtRNA2-1/Pre-miR-886 identity is still controversial, it was shown to be epigenetically controlled, presenting both tumor suppressor and oncogenic function in different cancers. Here, we study for the first time the role of nc886 in prostate cancer.
Nc886 promoter methylation status and its correlation with patient clinical parameters or DNMTs levels were evaluated in TCGA and specific GEO prostate tissue datasets. Nc886 level was measured by RT-qPCR to compare normal/neoplastic prostate cells from radical prostatectomies and cell lines, and to assess nc886 response to demethylating agents. The effect of nc886 recovery in cell proliferation (in vitro and in vivo) and invasion (in vitro) was evaluated using lentiviral transduced DU145 and LNCaP cell lines. The association between the expression of nc886 and selected genes was analyzed in the TCGA-PRAD cohort.
Nc886 promoter methylation increases in tumor vs. normal prostate tissue, as well as in metastatic vs. normal prostate tissue. Additionally, nc886 promoter methylation correlates with prostate cancer clinical staging, including biochemical recurrence, Clinical T-value and Gleason score. Nc886 transcript is downregulated in tumor vs. normal tissue -in agreement with its promoter methylation status- and increases upon demethylating treatment. In functional studies, the overexpression of nc886 in the LNCaP and DU145 cell line leads to a decreased in vitro cell proliferation and invasion, as well as a reduced in vivo cell growth in NUDE-mice tumor xenografts. Finally, nc886 expression associates with the prostate cancer cell cycle progression gene signature in TCGA-PRAD.
Our data suggest a tumor suppressor role for nc886 in the prostate, whose expression is epigenetically silenced in cancer leading to an increase in cell proliferation and invasion. Nc886 might hold clinical value in prostate cancer due to its association with clinical parameters and with a clinically validated gene signature.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Myeloid Neoplasms with germline predisposition become part of 2016 World Health Organization (WHO) classification of hematological malignancies since 2016. CCAAT/enhancer binding protein-alpha ...(CEBPA) is a myeloid transcription factor located in chromosome 19q. Acute myeloid leukemia (AML) with biallelic mutations of CEBPA AML with recurrent genetic abnormalities according to WHO classification. The inheritance of a germline CEBPA mutation predisposes to the development of AML with autosomal dominant inheritance. Familial CEBPA AML share characteristics with somatic CEBPA AML. However, a higher relapse incidence is reported. We present the case of a 46-years-old male with family history of acute leukemia who was diagnosed with single mutated CEBPA acute myeloid leukemia. The same mutation was found in two of his siblings. The clinical suspicion and proper diagnosis of familial cases is necessary, especially when a related allogenic transplant is indicated in order to select an adequate donor.
Focal and segmental glomerulosclerosis (FSGS) is a major cause of end-stage kidney disease. Recent advances in molecular genetics show that defects in the podocyte play a major role in its ...pathogenesis and mutations in inverted formin 2 (INF2) cause autosomal dominant FSGS. In order to delineate the role of INF2 mutations in familial and sporadic FSGS, we sought to identify variants in a large cohort of patients with FSGS. A secondary objective was to define an approach for genetic screening in families with autosomal dominant disease. A total of 248 individuals were identified with FSGS, of whom 31 had idiopathic disease. The remaining patients clustered into 64 families encompassing 15 from autosomal recessive and 49 from autosomal dominant kindreds. There were missense mutations in 8 of the 49 families with autosomal dominant disease. Three of the detected variants were novel and all mutations were confined to exon 4 of INF2, a regulatory region responsible for 90% of all changes reported in FSGS due to INF2 mutations. Thus, in our series, INF2 mutations were responsible for 16% of all cases of autosomal dominant FSGS, with these mutations clustered in exon 4. Hence, screening for these mutations may represent a rapid, non-invasive and cost-effective method for the diagnosis of autosomal dominant FSGS.
Rigid polyurethane (RPU) foams have been synthesized using lignin-based polyols obtained by oxypropylation of four distinct lignins (Alcell, Indulin AT, Curan 27-11P, and Sarkanda). Polyol ...formulations with two lignin/propylene oxide/catalyst content (L/PO/C) ratios were chosen (30/70/2 and 20/80/5). RPU foams have been prepared with a polyol component that incorporates the lignin-based one at contents ranging from 25 to 100%. A 100% commercial polyol-based (Lupranol® 3323) RPU foam was also prepared and used as the reference. RPU foams were characterized in terms of density, compressive modulus, and conductivity. Cell morphology and size estimation were accessed by scanning electron microscopy. Moreover, biodegradation of the Alcell- and Indulin AT-based foams was evaluated using respirometry tests in liquid and solid media. The Alcell- and Indulin AT-based polyols together with the 20/80/5 Curan 27-11P-based one led to RPU foams with properties quite similar to those of the reference homolog. Biodegradation seems to be, particularly, favored if using Indulin AT-based polyols mixed with Lupranol® 3323.
Focal and segmental glomerulosclerosis (FSGS) is a major cause of end-stage kidney disease. Recent advances in molecular genetics show that defects in the podocyte play a major role in its ...pathogenesis and mutations in inverted formin 2 (
INF2
) cause autosomal dominant FSGS. In order to delineate the role of
INF2
mutations in familial and sporadic FSGS, we sought to identify variants in a large cohort of patients with FSGS. A secondary objective was to define an approach for genetic screening in families with autosomal dominant disease. A total of 248 individuals were identified with FSGS, of whom 31 had idiopathic disease. The remaining patients clustered into 64 families encompassing 15 from autosomal recessive and 49 from autosomal dominant kindreds. There were missense mutations in 8 of the 49 families with autosomal dominant disease. Three of the detected variants were novel and all mutations were confined to exon 4 of
INF2
, a regulatory region responsible for 90% of all changes reported in FSGS due to
INF2
mutations. Thus, in our series, INF2 mutations were responsible for 16% of all cases of autosomal dominant FSGS, with these mutations clustered in exon 4. Hence, screening for these mutations may represent a rapid, non-invasive and cost-effective method for the diagnosis of autosomal dominant FSGS.
La identificación de componentes funcionales clave para diversos bioprocesos de interés industrial ha permitido seleccionar aislamientos
adaptados a condiciones ambientales extremas en tres especies ...de hongos del género Penicillium. Dichos aislamientos fueron evaluados in vitro para caracterizar su potencial como componentes de un consorcio microbiano aplicable en biorremediación de efluentes industriales que contienen residuos lignocelulósicos. Los resultados de la anotación de secuencias genómicas disponibles para una de las especies identificadas apuntan a la existencia de genes con alta similaridad respecto a los existentes en diversos hongos considerados como referencia en materia de
degradación de lignina en ambientes naturales. Las anotaciones funcionales propuestas a partir de secuencias accesibles –identificadas
a través de la base de datos Fungal Oxidative Lignin Enzymes– podrían contrastarse con los resultados experimentales para cepas creciendo en diferentes medios con lignina, representando ambientes industriales extremos. Mediante este trabajo se propone el ensamblado de Bioinfo_eXtrema como parte de un enfoque bioinformático centrado en la selección de consorcios de extremófilos para aplicaciones en biotecnología industrial, combinando diversas técnicas de minería de datos –integradas a través del Waikato Environment for Knowledge Analysis– para facilitar la integración de información molecular disponible e indicadores funcionales relevantes para aplicaciones en biorremediación.
El estudio de vías alternativas con mayores rendimientos y bajos costos es en estos días el foco de estudio en el tema Bioetanol, por tal motivo, en el presente trabajo se utilizaron dos cepas de ...hongos filamentosos; Trichoderma harzianum y Pleurotus ostreatus, actuando en diferentes sustratos residuales; orujo de uva, aserrín y torta de girasol provenientes de diferentes industrias nacionales, con el fin de establecer un sistema de evaluación de procesos conjuntos para la producción de alcohol a partir de microorganismos lignocelulósicos. En el diseño de estudio se contemplan la realización de una Presacarificación, con el objetivo de predigerir los sustratos, de forma de homogeneizar los diferentes sustratos acortando de esta forma las etapas posteriores; una Sacarificación enzimática utilizando el extracto de celulasas fúngicas obtenidas por Fermentación semi sólida en el proceso de Presacarificación; y un proceso de Fermentación, el cual involucra un microorganismo termoestable; Kluyveromyces marxianus (NRRL Y-665), de tal forma que permita reunir los procesos de Sacarificación y Fermentación en forma simultánea.
De acuerdo a los resultados obtenidos podemos establecer que el sistema empleado de FSS previa presacarificación es un buen sistema para la producción de azúcares fermentables y alcohol. Los estudios comparativos realizados con diferentes sustratos demuestran que cuando el soporte es orujo de uva o torta de girasol, se utiliza un mayor porcentaje de los azúcares fermentables disponibles, aproximadamente un 50%.
Los productos de degradación, resultado de la presacarificación, pueden afectar al microorganismo y actuar como potenciales inhibidores de la fermentación, por lo que es crítico realizar estudios que determinen estos productos de degradación y los mecanismos para su reducción. Podemos concluir que el sistema utilizado es efectivo para el almacenamiento de la biomasa en forma estable en el mismo proceso de presacarificación.AbstractThe study of alternative routes with better efficiency and low costs is the focus of study in Bioethanol nowadays. For this reason, in this paper we use two kind of filamentous fungi; Trichoderma harzianum and Pleurotus ostreatus, cultivating them in different kind of residual sustrates; as grape pomace, sawdast and sunflower cake provided by national industries, to establish an evaluation system for the the alcohol production process by lignocellulitic microorganisms. In this study, we contemplate three assays; a Presaccharification assay to reduce the saccharification time by predigesting the substrates; an enzymatic saccharification assay using the cellulases produced by the semi solid fermentation of the presaccharification process, and a fermentation assay which involved a thermostable microorganism; Kluyveromyces marxianus (NRRL Y-665) for a simultaneous Saccharification and Fermentation assay. From the results we could conclude that the system used is suitable for the production of reducing sugars and alcohol. Comparative studies using different substrates demonstrate that there is a great use of reducing sugars when the matrix is grape pomace or sunflower cake, roughly a 50%. The subproducts from presaccharification can affect the microorganisms and act as inhibitors of the process, which makes critical the study of this degradation products and how to reduce them . Finally, we can conclude that this system is effective for biomass storage in a stable way and in the same presaccharification process.
La microencapsulación de compuestos de actividad biológica (ADN, fármacos, proteínas, probióticos, enzimas, etc.), desde el punto de vista tecnológico, podría definirse como el proceso de ...recubrimiento de dichos compuestos, bajo la forma de moléculas, partículas sólidas o glóbulos líquidos, con materiales de distinta naturaleza, para dar lugar a partículas de tamaño micrométrico. Uno de los polímeros naturales más utilizados para la producción de microesferas es el quitosano (?-1,4- glucosamina). Diversos métodos han sido propuestos para la producción de microcápsulas, divididos en tres grupos: procesos físicos, procesos químicos y procesos físico-químicos. En el presente trabajo se ensayaron distintas metodologías para la producción de microesferas y microcápsulas de quitosano. Según la metodología empleada se obtuvieron distintos tipos de esferas en lo que respecta a tamaño y densidad principalmente. Las micropartículas obtenidas se evaluaron mediante microscopía óptica, electrónica de barrido, así como se realizó la evaluación de su estabilidad y liberación del agente encapsulado. AbstractThe microencapsulation process of agents with biological activity (such as DNA, pharmaceuticals, proteins, probiotics, enzymes, etc.), from the technological view, could be defined as the coating process of those agents, under a molecular form, solid particles, or liquid globules, with materials of different nature, that gives particles particles of micrometric size. One of the most used natural polymers for the production of microspheres is chitosan (?-1,4-glucosamine). Various methods have been proposed for the production of microcapsules, divided into three groups: physical processes, chemical processes, and physico-chemical processes. In this work, it were assayed different methodologies for the production of chitosan microspheres and microcapsules. Depending on the methodology used, were obtained differente types of spheres in reference to size and density. The microparticles produced were evaluated with optic microscopy, scanning electronic microscopy, so as were evaluated its stability and liberation of the encapsulated agent.
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