1,720,980 research outputs found
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
Gene dynamics of maturation in endogenous and pluripotent stem cell-derived cardiomyocytes
Get PDFA primary limitation in the clinical application of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) is the failure of these cells to achieve full functional maturity. In vivo, cardiomyocytes undergo numerous adaptive changes during perinatal maturation. By contrast, PSC-CMs fail to fully undergo these developmental processes, instead remaining arrested at an embryonic stage of maturation. To date, however, the precise mechanisms by which directed differentiation differs from endogenous development, leading to consequent PSC-CM maturation arrest, are unknown. The advent of single cell RNA-sequencing (scRNA-seq) has offered great opportunities for studying CM maturation at single cell resolution. However, postnatal cardiac scRNA-seq has been limited owing to technical difficulties in the isolation of single CMs. Additionally, cross-study comparison is limited by dataset specific batch effects. In this dissertation, I first established large particle fluorescence-activated cell sorting (LP-FACS) for isolation of viable single adult CMs. I secondly developed transcriptomic entropy as a robust, batch effect-resistant approach to quantifying CM maturation. With these and other computational tools, I investigated gene expression trends in endogenous and PSC-derived CMs. I first generated an scRNA-seq reference of mouse in vivo CM maturation with extensive sampling of perinatal time periods. I subsequently generated isogenic embryonic stem cells and created an in vitro scRNA-seq reference of PSC-CM directed differentiation. Through computational analysis, I identified a perinatal iimaturation program in endogenous CMs that is poorly recapitulated in vitro. By comparison of these trajectories with previously published human datasets, I identified a network of nine transcription factors (TFs) whose targets are consistently dysregulated in PSC-CMs across species. Notably, I demonstrated that these TFs are only partially activated in common ex vivo approaches to engineer PSC-CM maturation. This dissertation represents the first direct comparison of CM maturation in vivo and in vitro at the single cell level. Moreover, the findings and tools developed here can be leveraged towards improving the clinical viability of PSC-CMs
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
CLONIDINE-MEDIATED CELL CYCLE RE-ENTRY AND METABOLIC REPROGRAMMING IN HIPSC-DERIVED CARDIOMYOCYTES
No full textBackground: Owing to the poor regenerative potential of the adult human heart, cardiomyocyte (CM) loss following myocardial infarction is a major contributor to progressive cardiac dysfunction. Clonidine, a clinically approved α2-adrenergic agonist, has been previously implicated in promoting CM cell cycle re-entry; however, its mechanisms have yet to be defined. This study investigated the proliferative and metabolic effects of clonidine in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and engineered heart tissues (EHTs).
Methods: Live cell cycle imaging was conducted using a PIP-FUCCI adenoviral construct to monitor changes in cell cycle dynamics following clonidine treatment. Mitochondrial function was evaluated through Seahorse XF mitochondrial stress testing, while a phospho-kinase array was used to identify activated signaling pathways. Lastly, functional outcomes were measured in 3D EHTs by quantifying spontaneous contraction force, frequency, and qualitative PIP-FUCCI expression.
Results: In this study, we found that clonidine induced a dose- and time-dependent increase in CM cell cycle re-entry as evidenced by a shift from G1 to G2/M phases. Interestingly, mitochondrial respiration also increased in a dose-dependent manner, resulting in a significant increase in basal, maximal, and ATP-linked oxygen consumption. The cell cycle and metabolic-induced changes correlated with activation of the Akt–mTOR, RSK–CREB, and JAK–STAT3 pathways. Despite enhanced mitochondrial metabolism, clonidine did not improve contractile force in EHTs; however, it significantly reduced EHT contraction frequency, which is consistent with its known chronotropic effects. Qualitative analysis of PIP-FUCCI expressing EHTs revealed similar effects to 2D models, whereby clonidine enhanced S/G2/M phase expression.
Conclusion: These findings indicate that clonidine promotes hiPSC-CM cell cycle re-entry and enhances mitochondrial oxidative metabolism through activation of key proliferative and metabolic signaling pathways. These results provide a foundation for future studies aimed at optimizing combinatorial strategies for cardiac regeneration
Hedgehog Signals Regulate The Proliferation Of Cardiac Progenitor Cells In Pharyngeal Arches
Get PDFCongenital heart disease (CHD) is one of the most common live birth defects. The study of its underlying molecular and genetic mechanisms is crucial to our understanding of the origin of CHD and to the improvement of existing treatments. Previous studies have shown the importance of the Sonic Hedgehog (Shh) signaling pathway, among others, in the embryonic development of heart. Shh from distinct pulmonary and pharyngeal endoderm modulates second heart field (SHF) development and atrial septation. We provided evidence that the pharyngeal ectoderm may be another source of the Hedgehog signal. The conditional knockout of Shh and its paralog, Indian Hedgehog (Ihh), led to hypoplastic hearts missing the right ventricle and part of the outflow tract in embryonic day 9.5 mice. We used mouse embryonic stem cells (mESCs) to study how Hedgehog signaling controls the proliferation of SHF cardiac progenitor cells (CPCs), a potential contributing factor to the hypoplastic heart. By treating SHF CPCs with Hedgehog agonist and antagonist, we observed that Hedgehog activation increased proliferation within 24 hours after treatment while Hedgehog inhibition had the opposite effect. Furthermore, the heart phenotypes observed in Shh mutants are similar to those observed in mice that model Down syndrome (here, “Down syndrome mice). Disruption of Shh signaling in Down syndrome mice resulted in increased frequencies of complete atrioventricular septal defect (AVSD) in which the dorsal mesenchymal protrusion was absent. Further, we examined the interactions between Hedgehog signaling and trisomy in DS mice and identified two genes orthologous to chromosome 21, Ripk4 and Grik1, that were misregulated beyond the expected 50% increase in expression level. In mESC, we found that Grik1 overexpression was correlated with downregulation of Ptch1, a Hedgehog pathway gene, at the cardiomyocyte stage. The activation of Hedgehog signaling suppressed Grik1 transcriptional expression. The knockdown of Hedgehog pathway genes Gli1 and Gli2 resulted in normal the Grik1 level back control level. This indicates a potential regulatory interaction between Hedgehog signaling and trisomy for Grik1
UNDERSTANDING CARDIOMYOCYTE DIFFERENTIATION FROM PLURIPOTENT STEM CELLS
Get PDFStem cells have the potential of becoming all kinds of cell types and are serving as a powerful tool in scientific research and clinical purposes. With the discovery of Yamanaka factors(Takahashi & Yamanaka, 2006), we are able to make induced pluripotent stem cells from somatic cells, which further opened up various possibilities for studying diseases, mechanisms, and regenerative medicine.
Of all the exciting research areas, we are interested in using stem cells to understand cardiac development and maturation better. The heart is one of the least regenerative organs in our body, and thus they cannot repair themselves when damaged. The limited number of transplantable hearts and tissues leads to the urgent need to find ways to generate cardiomyocytes in vitro.
Emerging studies of stem cell-derived cardiomyocytes have shown promise in multiple applications and attracted significant interest. However, due to the poorly understood embryonic development and maturation process of cardiomyocytes, we currently lack the ability to generate mature adult cardiomyocytes from pluripotent stem cells. This addresses the necessity of studying and improving cardiomyocyte differentiation.
This thesis describes the cardiomyocyte differentiation process in two projects. The first project aims to generate early mouse cardiac mesodermal cells for blastocyst injection and the second project aims to differentiate an Alström syndrome(AS) patient-derived iPSC line into cardiomyocytes for proliferation studies. In this thesis, cardiomyocytes were successfully generated from the two stem cell lines using different protocols. Factors that may affect differentiation were discussed and optimized. The cardiomyocytes generated will be used in future experiments for the two projects
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