1,720,975 research outputs found
Mapping the heterogeneity of the human senescent proteome
No full textCellular senescence is a unique response to sublethal stress characterized by at least two elements: persistent cell cycle arrest and a senescence-associated secretory phenotype (SASP). Recent evidence suggests a close link between senescence and aging, as selective elimination of senescent cells in mice improves longevity and overall health. Therefore, there is increased interest in identifying markers to develop drugs (senolytics) that selectively eliminate senescent cells without harming healthy, proliferating cells. However, senescent phenotypes vary across cell types and inducers, creating a need for tissue-specific markers of senescence. To this “senescence catalog” has three aims: 1) Identify protein and RNA markers of senescence; 2) Compare across models to find overlapping markers; and 3) Validate markers with scRNA-seq and IHC in culture and in mice.National Institutes of Health (NIH) Intramural Research Training Award (IRTA)
NIH Intramural Research Program (IRP
CIRCULATING BIOMARKERS OF SENESCENCE REVEAL HIGH RESOLUTION HEALTH STATUS AND TRAJECTORIES IN HUMAN LONGITUDINAL STUDIES
No full textCellular senescence becomes more common with age and is thought to be a key contributor to age and age-related disease. One key aspect of senescence that facilitates its deleterious effect is the pro-inflammatory cytokines, among other proteins that are expressed and secreted by senescent cells, known as the senescence-associated secretory phenotype (SASP). In recent years, the proteome has been tracked in circulating plasma and showed associations with clinical traits and disease. These findings present the captivating possibility that the plasma proteome could be leveraged as a noninvasive diagnostic tool in clinical settings. Considering that senescence is a key hallmark of aging, the SASP could hold unique clinical relevance in circulation. One key challenge in similarly assessing senescence burden in circulation is that SASP are numerous and heterogeneous by cell type and induction method. Though some tissue-specific and canonical SASP have been examined in circulation, clinical associations of the broad range of tissue-specific SASP have been largely uncharacterized. This study undertakes a comprehensive investigation into clinical associations of tissue-specific senescence proteins in circulating plasma in two longitudinal studies, including 1275 individuals (ages 22-96) from the Baltimore Longitudinal Study of Aging (BLSA) and 997 individuals (ages 21-98) from the Italian Invecchiare in Chianti study (InCHIANTI). Tissue-specific senescence markers are identified from 15 total cell types including monocytes, astrocytes, and renal endothelial cells, among many others. These senescence signatures were then assessed for associations with a broad range of age-related clinical parameters. Senescence signatures were associated with a broad range of clinical traits in both the BLSA and InCHIANTI, and tissue-unique senescence signatures showed unique clinical relevance. For instance, kidney senescence signatures showed the strongest association with kidney disease. Additionally, PBMC senescence burden showed strong associations with multiple clinical parameters. These results suggest that senescence in immune cells may play an important role in age-related decline and demonstrate that individual senescence burden can be modeled with higher resolution on the organ-specific level than previously determined. This study extensively characterizes associations between circulating senescence signatures and clinical traits in humans and identifies biomarkers of senescence that can inform future clinical study
CIRCULATING BIOMARKERS OF SENESCENCE REVEAL HIGH RESOLUTION HEALTH STATUS AND TRAJECTORIES IN HUMAN LONGITUDINAL STUDIES
No full textCellular senescence becomes more common with age and is thought to be a key contributor to age and age-related disease. One key aspect of senescence that facilitates its deleterious effect is the pro-inflammatory cytokines, among other proteins that are expressed and secreted by senescent cells, known as the senescence-associated secretory phenotype (SASP). In recent years, the proteome has been tracked in circulating plasma and showed associations with clinical traits and disease. These findings present the captivating possibility that the plasma proteome could be leveraged as a noninvasive diagnostic tool in clinical settings. Considering that senescence is a key hallmark of aging, the SASP could hold unique clinical relevance in circulation. One key challenge in similarly assessing senescence burden in circulation is that SASP are numerous and heterogeneous by cell type and induction method. Though some tissue-specific and canonical SASP have been examined in circulation, clinical associations of the broad range of tissue-specific SASP have been largely uncharacterized. This study undertakes a comprehensive investigation into clinical associations of tissue-specific senescence proteins in circulating plasma in two longitudinal studies, including 1275 individuals (ages 22-96) from the Baltimore Longitudinal Study of Aging (BLSA) and 997 individuals (ages 21-98) from the Italian Invecchiare in Chianti study (InCHIANTI). Tissue-specific senescence markers are identified from 15 total cell types including monocytes, astrocytes, and renal endothelial cells, among many others. These senescence signatures were then assessed for associations with a broad range of age-related clinical parameters. Senescence signatures were associated with a broad range of clinical traits in both the BLSA and InCHIANTI, and tissue-unique senescence signatures showed unique clinical relevance. For instance, kidney senescence signatures showed the strongest association with kidney disease. Additionally, PBMC senescence burden showed strong associations with multiple clinical parameters. These results suggest that senescence in immune cells may play an important role in age-related decline and demonstrate that individual senescence burden can be modeled with higher resolution on the organ-specific level than previously determined. This study extensively characterizes associations between circulating senescence signatures and clinical traits in humans and identifies biomarkers of senescence that can inform future clinical study
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
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