1,720,973 research outputs found
An analysis of document viewing patterns of Web search engine users
No full textWeb Mining is moving the World Wide Web toward a more useful environment in which users can quickly and easily find the information they need. Web Mining uses document content, hyperlink structure, and usage statistics to assist users in meeting their needed information. This book provides a record of current research and practical applications in Web searching. It includes techniques that will improve the utilization of the Web by the design of Web sites, as well as the design and application of search agents. This book presents research and related applications in a manner that encourages additional work toward improving the reduction of information overflow, which is so common today in Web search results
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
A Novel Regulatory Function for p130 in Adipocyte Fatty Acid Metabolism
Get PDFUnderstanding the complex control mechanisms governing fatty acid synthesis and mobilization holds prognostic and therapeutic potential in treating metabolic diseases such as obesity and diabetes. Our data has uncovered a novel function for the transcriptional co-repressor p130 in adipocytes. In particular, we found that the subcellular localization of p130 supports fatty acid metabolism. Indeed, stimulating lipogenesis increased p130 levels in the mitochondria. Here it interacted at the D-loop regulatory region of mitochondrial DNA, repressing genes involved in oxidative phosphorylation. This could allow the intermediates of the TCA cycle to be utilized for lipid synthesis in lieu of energy production. Conversely, inducing lipolysis via 3-adrenergic activation in white adipocytes or a physiological challenge imposed by fasting, decreased p130 levels in the mitochondria, concomitant with increased mitochondrial-encoded gene expression. Unexpectedly, 3-adrenergic stimulation showed the reverse effect in brown adipocytes. Our results provide valuable insight for deconstructing the intricate metabolic framework of adipocytes
A non-canonical role for p107 in muscle stem cell fate decisions
No full textThe regenerative potential of skeletal muscle is attributed to the presence of resident muscle stem cells known as satellite cells (SCs). After activation SCs have two fates, either to differentiate into new muscle or self-renew to replenish their population. Dysregulation in favor of one outcome over the other has been implicated in loss of muscular regenerative capacity. Mitochondrial metabolism has recently emerged as a regulator of SC fate decisions. We uncovered a non-canonical mitochondrial role for retinoblastoma-like protein 1 (Rbl1, p107) in manipulating fate decisions through its effect on mitochondrial dynamics. We find that in the absence of mitochondrially localized p107, SCs display a higher rate of self-renewal, while also exhibiting higher mitochondrial connectivity. This was associated with increases in the mitochondrial fusion protein OPA1, as well as a loss in cellular acetylation. Taken together, these findings suggest that non-canonical p107 function in SCs controls their cell fate decisions
Metabolic Regulation by p107 (Rbl1) Influences Muscle Stem Cell Fate Decisions
Get PDFSkeletal muscle has a remarkable property of effective muscle fiber regeneration that maintain their normal physiology due to the presence of the adult muscle stem cells known as the satellite cells (SCs). The role of SCs is crucial, as myofiber turnover is an ongoing process during the lifetime of an individual to maintain proper muscle tissue viability. However, muscle wasting found in diseases such as muscular dystrophy and disorders that occur during the ageing process are associated with impaired SC function. Indeed, these complications are linked to compromised SC fate decisions for activation, self-renewal and commitment to muscle progenitor cells (MPs), which are characterized by diminished numbers. Thus, understanding the control pathways that impact SC fates is essential to improve their integrity for health and to benefit muscle diseases and disorders. Central to sustaining different SC fates is the regulation of energy generation between glycolysis in the cytoplasm and oxidative phosphorylation (Oxphos) in the mitochondria. However, the mechanisms that connect these energy provisioning centers to control cell behaviour remain obscure. Herein, our results reveal a mechanism by which mitochondrial-localized transcriptional co-repressor p107 governs MP proliferative rate, under the control of NAD+/NADH ratio. We found p107 directly interacts at the mitochondrial DNA promoter repressing mitochondrial-encoded genes. This reduces the mitochondrial ATP generation capacity, by limiting the electron transport chain complex formation. Importantly, the amount of ATP generated by the mitochondrial function of p107 is directly associated to the cell cycle rate in vivo and in vitro. This is exemplified by absence of p107 that drastically increased cell cycle progression and MP proliferation capacity through enhancement of ATP generation. Oppositely, forced expression of p107 in the mitochondria blocked cell cycle progression in vitro as a consequence of dampened ATP generation. Notably, Sirt1, whose activity is dependent on the cytoplasmic by-product of glycolysis, NAD+, directly interacts with p107 impeding its mitochondrial localization and function. Deletion of Sirt1 increased p107 mitochondrial localization, decreased MP mitochondrial Oxphos generation concomitant with attenuated cell cycle progression. Increasing the activity of Sirt1 had the converse effect on p107 function. In addition, we also showed that p107 genetically deleted skeletal muscle contained significantly more quiescent SCs, indicative of a better self-renewal ability. As a first step to test the physiological role of p107 on SCs and MPs, we assessed exercise in humans. We found p107 protein levels were inversely correlated with enhanced mitochondrial Oxphos following endurance exercise in skeletal muscle that might also occur in SCs. These novel results establish a new paradigm to manipulate muscle stem cell fate decisions that are impaired in many diseases and disorders
A Novel Protective Role for p130 in Neuron Oxidative Stress
Get PDFThe human brain is the most energy-consuming and highly oxidative organ in the body. It generates high levels of mitochondrial reactive oxygen species (ROS), damaging proteins and DNA. This is evident in neurodegenerative diseases and aging where the brains defence mechanisms prove insufficient. We provide insight into a novel mechanism of ROS defence in the brain, mediated via p130 that limits oxidative phosphorylation. Conditions of increased metabolic stress or treatment of neurons with ROS inducing agent resulted in mitochondrial localization of p130 in neurons. In the mitochondria, p130 bound to mitochondrial DNA and was associated with decreased mitochondrial gene expression. This resulted in decreased ATP production, thus limiting ROS generation. Our results highlight a new understanding of transcriptional regulation of the mitochondrial genome by the nuclear transcriptional corepressor p130. This might serve as a potential mechanism to control ROS production of neurons in response to increased metabolic stress
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
Stem Cell Bioenergetics: A Novel Regulatory Mechanism For p107 in Adipocyte Lineage Fates
Get PDFThe transcriptional co-repressor p107 has previously been shown to determine the metabolic fate of differentiated mesenchymal stem cells and their progenitors in a cell autonomous manner. Importantly, our new data shows that p107 influences stem cell fate decisions by its nuclear re-localization that results in regulating the bioenergetic status of the cells during G0/G1 phase of the cell cycle. In particular, p107 depleted primary stem and progenitor cells at G0/G1 undergo profound metabolic alterations including anaerobic glycolysis and significantly increased respiration. Our results show that p107 KD and KO stem cells and progenitors have an inefficient malate-aspartate shuttle, which decreases the availability of NADH into the mitochondria. Additionally, we found significantly elevated levels of two enzymes that enhance glycolysis, LDHa and PDK2. The effect of bioenergetics on adipocyte lineage fates is evident from inhibition of anaerobic glycolysis, which prevented the brown-type differentiation potential of p107 KD stem cell lines
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