1,721,060 research outputs found
IMAGING PHOSPHOLIPASE D ACTIVITIES IN LIVE CELLS WITH A REAL-TIME, BIOORTHOGONAL APPROACH AND ITS APPLICATIONS TO UNDERSTAND CELL SIGNALING AND PHOSPHOLIPID TRAFFICKING
No full text226 pagesLocalized production of signaling agents is an essential feature for living cells. Many of these signaling molecules are lipid entities. However, due to their hydrophobic nature and highly diverse cellular functions, certain potent, low-abundance lipids that act as signaling agents remain understudied with traditional biochemical techniques. Thus, the advancement of modern chemical biology tools represents a promising perspective to tackle these complex biological problems. Chapter 1 summarizes the challenges and recent advancement to study phospholipid signaling and discusses its relevance towards cell signaling and lipid trafficking. In Chapter 2, the author discusses the design, synthesis and characterization of a novel, bioorthogonal chemistry-based strategy, termed RT-IMPACT, to image the biosynthesis of a specific signaling lipid called phosphatidic acid (PA). With fast chemical kinetics and optimal enzyme specificity, PA produced by phospholipase D (PLD) enzyme activity can be visualized in living cells in real-time. The author further demonstrates that RT-IMPACT is capable of accurately reporting subcellular locations of PA production in response to different upstream stimuli. In Chapter 3, the author applies RT-IMPACT tools to investigate PTHR signaling that are previously underexplored. The author shows that PLD activation is specifically downstream of PTHR-Gq protein signaling. Moreover, the Gq signaling pathway, in stark contrast to the Gs pathway, is transient and localized on the plasma membrane as revealed by time-resolved imaging of PLD activities. Lastly, through inhibition of endocytic pathways, a competitive relationship between the Gq and Gs pathway is revealed. In Chapter 4, the author characterizes a family of lipid transfer proteins—ESyts—that are responsible for trafficking of unnatural fluorescent lipids from PM to ER. A positive correlation between the expression levels of ESyts and trafficking rates from PM to ER is established. Next, through protein engineering, lipid transfer activities of ESyts are shown to be directly responsible for removal of unnatural fluorescent lipids from the PM. In the final chapter, the author summarizes the major findings and significance of this work towards understanding of physiologically relevant pathways. Several potential future directions, including screening for potential upstream stimuli and identifying other lipid transfer proteins, are briefly described
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
METABOLISM-COUPLED PROTEIN POST-TRANSLATIONAL MODIFICATIONS IN C. ELEGANS AND MAMMALIAN MODELS
No full text382 pagesThe regulation of cellular processes is governed by intricate biochemical mechanisms, which often rely on metabolic feedback on protein function, for example, by way of product inhibition of enzymes and protein post-translational modifications (PTMs). PTMs are chemical modifications that occur on proteins after their synthesis, enabling rapid and often reversible functional responses to cellular and environmental changes. Most of the hundreds of known PTMs are derived from small molecule metabolites, with continued characterization efforts of the metabolome and PTMs deepening our understanding of related biological regulatory mechanisms that impact health and disease. This dissertation delves broadly into the coupling between metabolism and PTMs, exploring both the upstream metabolic events contributing to and the downstream pathways influenced by PTM dynamics.The first chapter, a review focusing primarily on recent examples from the past 3–4 years, demonstrates how the availability of a broad range of metabolites tightly controls functionally important PTMs. It emphasizes the chemical diversity of PTMs, the compartment-specific roles of metabolic enzymes in PTM occurrence, and the necessity of untargeted mass spectrometry-based approaches to uncover new PTM-involved regulatory mechanisms. The second chapter describes discovery of a family of conserved metabolites, N-acylspermidines, which were uncovered from mass feature-level untargeted comparative metabolomic analyses of wildtype Caenorhabditis elegans (C. elegans) and a knock-out mutant of the mitochondrial sirtuin sir-2.3. N-acylspermidines were found to be downstream of mitochondrial sirtuin function and have negative impacts on C. elegans lifespan and cancer cell proliferation. The third chapter focuses on protein fatty acylation in C. elegans, revealing distinct fatty acylation patterns at both amino acid type and protein levels. The monomethyl branched-chain 15-methylhexadecanoylation was found to be the most abundant cysteine fatty acylation. Using its clickable alkyne analog and other straight chain alkyne fatty acids, the author developed the first comprehensive fatty acylated proteome database for C. elegans. The fourth chapter introduces a novel PTM, the conjugation between lysine residue and electrophilic metabolite propionaldehyde, termed ‘C3-iminylation’. The protein-modifying propionaldehyde was found to be derived from cytochrome P450-mediated oxidation of omega-3 fatty acids, an essential nutrient of significant interest.2027-01-0
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
COMBINATORIAL ASSEMBLY OF MODULAR METABOLITES VIA CARBOXYLESTERASES IN NEMATODES
No full text335 pagesThe small molecule metabolites produced by living organisms play essential roles in nearly every aspect of their life history, including lifespan, development, and behavior. The identification of these small molecules and the discovery of their biosynthesis is key to understand the intra- and inter-organismal signaling pathways that exist within living systems and can offer insight into the function of related small molecules in orthologous organisms. In this dissertation, the author explores the combinatorial assembly of complex modular structures and how nematodes utilize building blocks derived from conserved catabolic, detoxification, and degradation pathways for the biosynthesis of modular metabolites. By utilizing comparative metabolomics of high-resolution mass spectrometry data, we were able to identify a novel class of modular metabolites, based on a glucoside core, that require a specific lysosome-related organelle and the activity of carboxylesterases for their biosynthesis. Caenorhabditis elegans are able to glucosylate endogenous and xenobiotic compounds forming glucosides. These glucosides are then further decorated by molecular moieties derived primarily from catabolic and detoxification pathways, such as amino acid degradation pathways, to form hundreds of different modular glucosides via carboxylesterases. We further demonstrate that these carboxylesterase-derived modular glucosides are involved in the starvation and stress response pathways in C. elegans. We show that this biosynthetic strategy to create chemical diversity from hijacking conserved detoxification mechanisms is shared with a related species of nematode, Caenorhabditis briggsae. While many aspects of modular metabolite biosynthesis and function remain to be elucidated, our results show that modular metabolites form an integral part of C. elegans metabolism and serve important biological roles. More generally, the work presented here demonstrates how untargeted comparative metabolomic analysis can be used to facilitate the annotation of the metabolic dark matter
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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