1,721,250 research outputs found
Studies on the expression and function of PIWI-interacting RNAs in prostate cancer with particular emphasis on piRNA-27619
No full textProstatakarzinom ist weltweit das häufigste Malignom des Mannes. Es existieren anatomisch, histopathologische und klinisch prognostisch relevante Parameter, aufgrund ihrer eingeschränkten Vorhersagekraft ist die Einschätzung des individuellen Risikoprofils jedoch weiterhin eingeschränkt. Daher wird intensiv nach Markern gesucht, die in der Lage sind, den klinisch sehr heterogen Tumor vor Therapieentscheidung besser zu charakterisieren. Die differenzielle Expression von onkogenen und tumorsuppressiven miroRNAs (miRNAs) wurde am Prostatakarzinom beschrieben, allerdings fanden bisher keine miRNA Profile als prognostisch relevante Biomarker den Einzug in die Klinik. Neben miRNAs rückten in den letzten Jahren die sogenannten „PIWI-interagierende RNAs“ (piRNAs) als weitere tumorassoziierte Gruppe von RNA Molekülen in den Fokus der onkologischen Grundlagenforschung. Über die Rolle von piRNAs in der Entwicklung und Progression des Prostatakarzinoms ist zurzeit noch wenig bekannt.
Ausgehend von einer bioinformatischen Datenbank basierten Suche konnte eine piRNA als potenziell diagnose- und prognoserelevante piRNA selektiert werden- die piR-27619. Anhand biochemischer sowie bioinformatischer Merkmale konnte ich die piR-27619 als piRNA charakterisieren. Zudem zeigte sich im Rahmen bioinformatischer Untersuchungen eine analoge Sequenz zu einer Lysin-tragenden tRNA, sodass die piR-27619 den „t-RNA derived RNA fragments“ untergeordnet werden kann. Zur Einordnung der (patho)-physiologischen Rolle der piR-27619 in der Genese und Progression des Prostatakarzinoms erfolgte die Analyse der piR-27619 Expression im prostatischen Tumorgewebe eines Hochrisikokollektivs. Es zeigte sich eine tendenzielle Heraufregulation der piR-27619 Expression in Primärtumoren des Hochrisiko-Kollektivs verglichen zu nicht malignen Hyperplasieproben. In lymphnodalen Metastasen von Prostatakarzinomen konnte eine statistisch signifikante Überexpression der piR-27619 verglichen zu Primärmalignom detektiert werden.
Auf dieser Beobachtung basierend erfolgte eine „loss of function“ Analyse durch anti-piR-27619 transfizierter Zellen in vitro. In der prostatischen Tumor-Zelllinien PC3, LNCaP sowie DU145 inhibiert die Herabregulation der piR-27619 signifikant die Proliferation bzw. induzierte Apoptose. Diese Beobachtung gilt nicht für die als relativ wenig magline eingestufte Prostatakarzinomzelllinie 22RV1.Die Analyse des Caspase 3/7 Signalwegs der piR-27619 inhibierten Prostatakarzinomzelllinien PC3 und LNCaP wies eine statistisch signifikante Caspase- abhängige Apoptoseinduktion nach. Untersuchungen des Zellzykluses demonstrierten einen Arrest der anti-piR-27619 transfizierter Prostatakarzinomzelllinie PC3 in der S-Phase des Zellzykluses.
Die Expressionsanalyse indizierte eine potenziell onkogene Funktion der piR-27619 im Prostatakarzinom, welche durch meine Erforschung der piR-27619 Funktion für die Proliferation, Apoptose und ungestörter Ablauf des Zellzyklus bestätigt werden konnte.
Die Überexpression der piR-27619 in lymphnodalen Metastasen, sowie das Entfallen ihrer onkogenen Funktion in der weniger malignen Prostatakarzinomzelllinie 22RV1 lassen auf eine potenzielle Bedeutung der piR-27619 besonders in aggressiven Formen des Prostatakarzinoms schliessen, die in weiterführenden Versuchen näher untersucht werden, um so ein besseres Verständnis für eine mögliche prognostische Relevanz der piR-27619 im Prostatakarzinom zu erlangen.Prostate cancer is the most common malignancy in men worldwide. While several anatomical, histopathological, and clinically prognostic parameters exist, their limited predictive power continues to restrict accurate individual risk assessment. Consequently, there is intense research interest in identifying novel biomarkers capable of better characterizing this clinically heterogeneous tumor prior to therapeutic decision-making.
Differential expression of oncogenic and tumor-suppressive microRNAs (miRNAs) has been demonstrated in prostate cancer; however, no miRNA profiles have yet been established as clinically relevant prognostic biomarkers. In recent years, so-called PIWI-interacting RNAs (piRNAs) have emerged as another tumor-associated class of RNA molecules attracting attention in cancer research. To date, little is known about the role of piRNAs in the development and progression of prostate cancer.
Based on a bioinformatic database search, one piRNA—piR-27619—was identified as a potentially diagnostic and prognostically relevant candidate. Biochemical and bioinformatic analyses confirmed the identity of piR-27619 as a bona fide piRNA. Moreover, bioinformatic investigations revealed sequence similarity to a lysine-bearing tRNA, suggesting that piR-27619 may belong to the class of tRNA-derived RNA fragments (tRFs).
To assess the (patho)physiological role of piR-27619 in prostate cancer development and progression, expression analyses were performed in tumor tissues from a high-risk cohort. A trend toward upregulation of piR-27619 expression was observed in primary tumors compared with samples of benign prostatic hyperplasia. In lymph node metastases, a statistically significant overexpression of piR-27619 was detected compared to primary carcinomas.
Based on these findings, a loss-of-function analysis was conducted using anti-piR-27619-transfected cells in vitro. In the prostate cancer cell lines PC3, LNCaP, and DU145, downregulation of piR-27619 significantly inhibited proliferation and induced apoptosis, whereas this effect was not observed in the less malignant 22RV1 cell line. Analysis of the caspase-3/7 pathway demonstrated a statistically significant caspase-dependent induction of apoptosis in piR-27619–inhibited PC3 and LNCaP cells. Cell cycle analysis revealed a S-phase arrest in anti-piR-27619–transfected PC3 cells.
These findings indicate a potentially oncogenic function of piR-27619 in prostate cancer, which was corroborated by the observed effects on proliferation, apoptosis, and cell cycle progression. The overexpression of piR-27619 in lymph node metastases, along with the loss of its oncogenic function in the less malignant 22RV1 cell line, suggests that piR-27619 may play a role particularly in aggressive forms of prostate cancer. Further studies are warranted to elucidate its molecular mechanisms and potential prognostic significance in prostate cancer
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
The neuroimmunological toll of nutrient absorption
No full textThe innate immune lymphocytes (ILCs), discovered about a decade ago, exhibit functional features of T cells but lack antigen‐specific receptors (ie, TCR). ILCs modulate mucosal immunity, inflammation, and tissue homeostasis.1 Among them, ILC3s express retinoid‐related orphan receptor γt (RORγt) transcription factor and produce IL‐22 and IL‐17, actively maintaining tissue homeostasis.RJS is funded by Ministerio de Economía y Competitividad (IJCI‐2016‐27619)
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