1,721,101 research outputs found
Interplay of Nanog and microRNAs in controlling stemness and proliferation in Neural Stem Cells
No full textThe maintenance of Neural Stem Cells (NSC) from different niches of embryonic or postnatal forebrain (subventricular zone and hippocampus) as well as cerebellum is promoted by a number of stemness genes (e.g. Nanog, Oct4, Sox2). Inspite of our good understanding of the mechanisms regulating these stemness drivers, there is a poor knowledge about their target genes, whereby stem cell features are regulated. We identify herein miR-17/92 cluster as a target of Nanog. Nanog controls miR-17/92 cluster by binding to the upstream regulatory region and enhancing its transcription in NSC. Whereas miR-17/92 expression is upregulated in NSC, it decreases alongside differentiation and cell maturation. MiR-17 family further enhances both clonogenicity and proliferation of NSC. Conversely, antagonizing miR-17 family yields an opposing effect. MiR-17 family has a number of potential targets involved in cell cycle and proliferation. We identify here the Transformation related protein 53-induced nuclear protein 1 (TRP53INP1), a proapoptotic stress-induced p53 target gene. MiR-17 family expression paralleled the reduced TRP53INP1 levels. Silencing TRP53INP1 in NSC enhances both self-renewal and proliferation. Infact the increase of Nanog and miR-17 family expression helps in transition from G1 to S phase of NSC cycle coinciding with the reduction of TRP53INP1. Collectively, Nanog via miR-17/92 cluster regulates NSC by silencing TRP53INP1. These findings allowed us to expand the regulatory circuitry of p53 signalling via Nanog in NSC and suggested the role of miRNAs in the maintenance of NSC.MARIE CURIE ESR FELLOWSHIP, FP7ITN HEALING Projec
Molecular Aspects of Cancer Cell Metabolism: Altered Glycolysis and Lipid Metabolism
No full textCancer cells have high proliferation rate and therefore require continuous energy source. Metabolic alteration in pathways like glycolysis and lipid metabolism gives a better chance of survival for cancer cells. Cancer cells produce lactic acid from glucose in the presence of oxygen and suppress tricarboxylic acid (TCA) cycle. This phenomenon is known as the Warburg effect. Cancer cells have the ability to perform de novo synthesis of lipids. These alterations in metabolism of cancer cells provide them multimodal advantages and differentiate them from normal cells. These altered metabolisms can be used for tracking and isolating the cancer cells from normal cell population and further can be targeted for cancer-specific treatment. In this chapter, we have highlighted the cancer cell advantages over normal cell in two specific pathways: Glycolysis and Lipid metabolism. These two strategic pathways are utilized by cancer cells for their survival and progression
Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections
Full text linkViral lower respiratory tract infection (vLRTI) is a leading cause of hospitalization and death in children worldwide. Despite this, no studies have employed proteomics to characterize host immune responses to severe pediatric vLRTI in both the lower airway and systemic circulation. To address this gap, gain insights into vLRTI pathophysiology, and test a novel diagnostic approach, we assayed 1,305 proteins in tracheal aspirate (TA) and plasma from 62 critically ill children using SomaScan. We performed differential expression (DE) and pathway analyses comparing vLRTI (n = 40) to controls with non-infectious acute respiratory failure (n = 22), developed a diagnostic classifier using LASSO regression, and analyzed matched TA and plasma samples. We further investigated the impact of viral load and bacterial coinfection on the proteome. The TA signature of vLRTI was characterized by 200 DE proteins (Padj <0.05) with upregulation of interferons and T cell responses and downregulation of inflammation-modulating proteins including FABP and MIP-5. A nine-protein TA classifier achieved an area under the receiver operator curve (AUC) of 0.96 (95% CI: 0.90-1.00) for identifying vLRTI. In plasma, the host response to vLRTI was more muted with 56 DE proteins. Correlation between TA and plasma was limited, although ISG15 was elevated in both compartments. In bacterial coinfection, we observed increases in the TNF-stimulated protein TSG-6, as well as CRP, and interferon-related proteins. Viral load correlated positively with interferon signaling and negatively with neutrophil-activation pathways. Taken together, our study provides fresh insights into the lower airway and systemic proteome of severe pediatric vLRTI and identifies novel protein biomarkers with diagnostic potential.IMPORTANCEWe describe the first proteomic profiling of the lower airway and blood in critically ill children with severe viral lower respiratory tract infection (vLRTI). From tracheal aspirate (TA), we defined a proteomic signature of vLRTI characterized by increased expression of interferon signaling proteins and decreased expression of proteins involved in immune modulation including FABP and MIP-5. Using machine learning, we developed a parsimonious diagnostic classifier that distinguished vLRTI from non-infectious respiratory failure with high accuracy. Comparative analysis of paired TA and plasma specimens demonstrated limited concordance, although the interferon-stimulated protein ISG15 was significantly upregulated with vLRTI in both compartments. We further identified TSG-6 and CRP as airway biomarkers of bacterial-viral coinfection, and viral load analyses demonstrated a positive correlation with interferon-related protein expression and a negative correlation with the expression of neutrophil activation proteins. Taken together, our study provides new insights into the lower airway and systemic proteome of severe pediatric vLRTI
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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