1,720,962 research outputs found
Epigenetic analyses in forensic medicine: future and challenges
Full text linkThe possibility of using epigenetics in forensic investigation has gradually risen over the last few years. Epigenetic changes with their dynamic nature can either be inherited or accumulated throughout a lifetime and be reversible, prompting investigation of their use across various fields. In forensic sciences, multiple applications have been proposed, such as the discrimination of monozygotic twins, identifying the source of a biological trace left at a crime scene, age prediction, determination of body fluids and tissues, human behavior association, wound healing progression, and determination of the post-mortem interval (PMI). Despite all these applications, not all the studies considered the impact of PMI and post-sampling effects on the epigenetic modifications and the tissue-specificity of the epigenetic marks. This review aims to highlight the substantial forensic significance that epigenetics could support in various forensic investigations. First, basic concepts in epigenetics, describing the main epigenetic modifications and their functions, in particular, DNA methylation, histone modifications, and non-coding RNA, with a particular focus on forensic applications, were covered. For each epigenetic marker, post-mortem stability and tissue-specificity, factors that should be carefully considered in the study of epigenetic biomarkers in the forensic context, have been discussed. The advantages and limitations of using post-mortem tissues have been also addressed, proposing directions for these innovative strategies to analyze forensic specimens
Epigenetic alterations in prescription opioid misuse: New strategies for precision pain management
No full textPrescription opioids are used for some chronic pain conditions. However, generally, long-term therapy has unwanted side effects which may trigger addiction, overdose, and eventually cause deaths. Opioid addiction and chronic pain conditions have both been associated with evidence of genetic and epigenetic alterations. Despite intense research interest, many questions about the contribution of epigenetic changes to this typology of addiction vulnerability and development remain unanswered. The aim of this review was to summarize the epigenetic modifications detected in specific tissues or brain areas and associated with opioid prescription and misuse in patients who have initiated prescribed opioid management for chronic non-cancer pain. The review considers the effects of opioid exposure on the epigenome in central and peripheral tissues in animal models and human subjects and highlights the mechanisms in which opioid epigenetics may be involved. This will improve our current understanding, provide the basis for targeted, personalized pain management, and thus balance opioid risks and benefits in managing chronic pain
Autophagy: A Player in response to Oxidative Stress and DNA Damage
Full text linkAutophagy is a catabolic pathway activated in response to different cellular stressors, such as damaged organelles, accumulation of misfolded or unfolded proteins, ER stress, accumulation of reactive oxygen species, and DNA damage. Some DNA damage sensors like FOXO3a, ATM, ATR, and p53 are known to be important autophagy regulators, and autophagy seems therefore to have a role in DNA damage response (DDR). Recent studies have partly clarified the pathways that induce autophagy during DDR, but its precise role is still not well known. Previous studies have shown that autophagy alterations induce an increase in DNA damage and in the occurrence of tumor and neurodegenerative diseases, highlighting its fundamental role in the maintenance of genomic stability. During DDR, autophagy could act as a source of energy to maintain cell cycle arrest and to sustain DNA repair activities. In addition, autophagy seems to play a role in the degradation of components involved in the repair machinery. In this paper, molecules which are able to induce oxidative stress and/or DNA damage have been selected and their toxic and genotoxic effects on the U937 cell line have been assessed in the presence of the single compounds and in concurrence with an inhibitor (chloroquine) or an inducer (rapamycin) of autophagy. Our data seem to corroborate the fundamental role of this pathway in response to direct and indirect DNA-damaging agents. The inhibition of autophagy through chloroquine had no effect on the genotoxicity induced by the tested compounds, but it led to a high increase of cytotoxicity. The induction of autophagy, through cotreatment with rapamycin, reduced the genotoxic activity of the compounds. The present study confirms the cytoprotective role of autophagy during DDR; its inhibition can sensitize cancer cells to DNA-damaging agents. The modulation of this pathway could therefore be an innovative approach able to reduce the toxicity of many compounds and to enhance the activity of others, including anticancer drugs
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
Discovering Non-Invasive Biomarkers Predictive of Opioid Use Disorder Treatment Response
No full textBACKGROUND: Opioid use disorder (OUD) continues to be the driving force behind drug overdoses in the United States, killing nearly 47,000 people in 2018 alone. The increasing presence of deadlier fentanyl analogues in the heroin drug supply are putting users at a greater risk for overdose than ever before. Admissions to treatment programs for OUD have also nearly doubled since 2006, yet relapse rates remain high. In response to these alarming statistics, developing approaches to reduce overdose deaths has become an area of high priority. As it is not yet known which patients are most likely to benefit from a specific treatment, there is a dire need to utilize new molecular tools to guide precision medicine approaches and improve treatment outcomes. Here we describe a proof-of-concept study evaluating plasma-derived extracellular vesicle (EV) signatures and how they differ in patients who responded to two pharmacologically contrasting treatments for OUD: the μOR agonist methadone, and the μOR antagonist naltrexone. METHODS: We obtained blood samples from patients with OUD who remained abstinent from illicit opioids for at least 3 months during treatment with methadone (n=5) and naltrexone (n=5), as well as matched healthy controls (n=5). EVs were isolated from plasma and histones were isolated from peripheral blood mononuclear cells (PBMCs). EVs were then analyzed for lipid and histone post-translational modification (PTM) content using liquid chromatography-mass spectrometry. EV miRNA cargo was determined by RNA sequencing. RESULTS: We found one lipid class and six miRNAs that differed significantly between the naltrexone group and the methadone and control groups. We also found that histone H3acK9acK14 was increasingly acetylated in PMBCs from both the methadone and naltrexone groups compared to controls. DISCUSSION: Naltrexone, which is used in treatment of OUD and other substance use disorders as well as disorders of impulse control, was found to have multiple potential corresponding molecular signatures that can be identified after long-term treatment. It remains to be seen if these markers can also be a good predictor for treatment response. In addition, significant gender differences in EV content are found between men and women with OUD, which supports the importance of examining changes in response to treatment in a gender informed way
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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