1,721,061 research outputs found
Metabolism as master of hematopoietic stem cell fate
No full textHSCs have a fate choice when they divide; they can self-renew, producing new HSCs, or produce daughter cells that will mature to become committed cells. Technical challenges, however, have long obscured the mechanics of these choices. Advances in flow-sorting have made possible the purification of HSC populations, but available HSC-enriched fractions still include substantial heterogeneity, and single HSCs have proven extremely difficult to track and observe. Advances in single-cell approaches, however, have led to the identification of a highly purified population of hematopoietic stem cells (HSCs) that make a critical contribution to hematopoietic homeostasis through a preference for self-renewing division. Metabolic cues are key regulators of this cell fate choice, and the importance of controlling the population and quality of mitochondria has recently been highlighted to maintain the equilibrium of HSC populations. Leukemic cells also demand tightly regulated metabolism, and shifting the division balance of leukemic cells toward commitment has been considered as a promising therapeutic strategy. A deeper understanding of precisely how specific modes of metabolism control HSC fate is, therefore, of great biological interest, and more importantly will be critical to the development of new therapeutic strategies that target HSC division balance for the treatment of hematological disease
Mitochondrial control of hematopoietic stem cell balance and hematopoiesis
No full textHematopoietic stem cells (HSCs) are stem cells from mesodermal derivation that reside in bone marrow and provide blood cells for the whole life of an adult individual, through a process called hematopoiesis. The long lasting support of HSCs for hematopoiesis is permitted by the fine regulation of quiescence and division output. Exit from the quiescent state is to produce a committed and/or stem daughter cells, in an event defined asymmetric or symmetric division. A deregulation in the proportion between asymmetric and symmetric divisions is critical in the appearance of hematological disorders ranging from bone marrow failure to hematological malignancies. Over the past years, several studies have indicated how the metabolism of HSCs is determinant in the regulation of HSC quiescence and commitment process. A metabolism shifted to the glycolytic pathway promotes HSCs quiescence and sustainment of hematopoiesis. Boosting mitochondrial respiration promotes the stem cell commitment followed by stem pool exhaustion, and minimal mitochondrial activity is required to maintain the HSCs quiescence. In the present review are discussed the most recent advances in comprehension of the roles of mitochondria in the hematopoiesis and in the division balance. © 2015, Higher Education Press and Springer-Verlag Berlin Heidelberg
Metabolism and HSC fate: what NADPH is made for
No full textMitochondrial metabolism plays a central role in the regulation of hematopoietic stem cell (HSC) biology. Mitochondrial fatty acid oxidation (FAO) is pivotal in controlling HSC self-renewal and differentiation. Herein, we discuss recent evidence suggesting that NADPH generated in the mitochondria can influence the fate of HSCs. Although NADPH has multiple functions, HSCs show high levels of NADPH that are preferentially used for cholesterol biosynthesis. Endogenous cholesterol supports the biogenesis of extracellular vesicles (EVs), which are essential for maintaining HSC properties. We also highlight the significance of EVs in hematopoiesis through autocrine signaling. Elucidating the mitochondrial NADPH-cholesterol axis as part of the metabolic requirements of healthy HSCs will facilitate the development of new therapies for hematological disorders
Membrane-potential compensation reveals mitochondrial volume expansion during HSC commitment
No full textProper control of mitochondrial function is a key factor in the maintenance of hematopoietic stem cells (HSCs). Mitochondrial content is commonly measured by staining with fluorescent cationic dyes. However, dye staining can be affected, not only by xenobiotic efflux pumps, but also by dye intake, which is dependent on the negative charge of mitochondria. Therefore, mitochondrial membrane potential (ΔΨmt) must be considered in these measurements because a high ΔΨmt due to respiratory chain activity can enhance dye intake, leading to the overestimation of mitochondrial volume. Here, we show that HSCs exhibit the highest ΔΨmt of the hematopoietic lineages and, as a result, ΔΨmt-independent methods most accurately assess the relatively low mitochondrial volumes and DNA amounts of HSC mitochondria. Multipotent progenitor stage or active HSCs display expanded mitochondrial volumes, which decline again with further maturation. Further characterization of the controlled remodeling of the mitochondrial landscape at each hematopoietic stage will contribute to a deeper understanding of the mitochondrial role in HSC homeostasis
The Road to Pathogenesis: Charting the Development of LSCs and Pre-LSCs
No full textThis eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac
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
<Articles>The Mechanism of Saifu Draft (割符) : Exchange, Distribution and Credit
No full text為替は遠隔地間の逆方向の送金関係の決済を、現金輸送を伴わずに同一地域内の代金決済に振り替えて行うこと、と定義される。よって、為替の一種である中世の割符を分析する際には送金関係の振替の構造を明らかにせねばならない。にもかかわらず、先行研究では割符という文書の動きばかりが注目され、振替の構造やしくみは検討されてこなかった。本稿では割符が、商品仕入原資等の「京都から地方へ」の送金と、荘園制に基づく「地方から京都へ」の貢納による送金という、遠隔地間の逆方向の送金関係を、割符の振出・決済という地域内の代金決済に振り替えるというしくみによって発行されていたことと、割符の振出地と支払地が同地かそれとも遠隔地かによって、「預かり文言型」・「為替文言型」という二種類に分類されること、を明らかにした。割符は地方から京都への貢納送金の手段であると同時に、遠隔地商人による京都から地方への仕入原資の送金、あるいは地方での借銭手段でもあった。商人たちは当時存在した都鄙間価格差を利用して利益をあげるために、割符を利用していたのである。このように割符とは、為替・流通・金融が組み合わさった取引であり、荘園制貢納と商品流通とを「送金関係の交換」によって互恵的に結びつける役割を果たしていたといえよう。Medieval draft transactions (saifu torihiki) were a form of economic exchange. Exchange has been defined as the act of transferring a cash settlement within one region without sending a cash remittance for settlement in the opposite direction between distant locations. Thus, in order to analyze these drafts, it is necessary to clarify the structure of the transfers. Despite this fact, previous studies have only focused on the movement of the drafts as documents. They have ignored what sort of remittances they were and how they were transferred. This study concentrates on those previously ignored aspects and clarities the following four points. First, in medieval Japan, there was a demand for remittances to be sent from the Kyoto to the outlying regions as funds to stock goods, etc. and also a demand for remittances to be sent from outlying regions to Kyoto based on the payment of annual tribute-tax from the manor system. Draft transactions were the mechanism for transferring cash settlements within a region by drawing or setting a draft for these two types of distant remittances. Second, the wording of the drafts can be distinguished into two types; one using the word deposit (azukari) and the other using a word for remittance (kawashi). In the former the location of the drafting and the payment were the same, but in the latter the locations differed and were removed from one another. Third, the draft was a method for remitting the annual tax from outlying regions to Kyoto, a method of remittance of funds for the purchase of goods from Kyoto to be sent to outlying regions by merchants in distant locations, and also a means of credit in outlying regions. Fourth, it was the merchants who issued these drafts. They obtained funds to purchase goods in regions where prices were low by draft transactions. And by selling goods in Kyoto where prices were high, they were able to increase their profits. The following conclusions can be drawn from these four points. Draft transactions were transactions interlinked with exchange, distribution, and credit. The role played by draft transactions was a mutually beneficial linkage of the tax from estates and the distribution of goods through the exchange of remittances
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