scholarly journals Transferrin is a major determinant of hepcidin expression in hypotransferrinemic mice

Blood ◽  
2011 ◽  
Vol 117 (2) ◽  
pp. 630-637 ◽  
Author(s):  
Thomas B. Bartnikas ◽  
Nancy C. Andrews ◽  
Mark D. Fleming

AbstractAs a central regulator of iron metabolism, hepcidin inhibits dietary iron absorption and macrophage iron recycling. Its expression is regulated by multiple factors including iron availability and erythropoietic activity. To investigate the role of transferrin (Tf) in the regulation of hepcidin expression by these factors in vivo, we employed the hypotransferrinemic (hpx) mouse. These Tf-deficient mice have severe microcytic anemia, tissue iron overload, and hepcidin deficiency. To determine the relationship of Tf levels and erythropoiesis to hepcidin expression, we subjected hpx mutant and control mice to a number of experimental manipulations. Treatment of hpx mice with Tf injections corrected their anemia and restored hepcidin expression. To investigate the effect of erythropoiesis on hepcidin expression, we suppressed erythropoiesis with blood transfusions or myeloablation with chemotherapeutic drugs. Transfusion of hpx animals with wild-type red blood cells led to increased hepcidin expression, while hepcidin expression in myeloablated hpx mice increased only if Tf was administered postablation. These results suggest that hepcidin expression in hpx mice is regulated both by Tf-restricted erythropoiesis and by Tf through a mechanism independent of its role in erythropoiesis.

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Li Song ◽  
Bin Luan ◽  
Qingrong Xu ◽  
Ruihe Shi ◽  
Xiufang Wang

Abstract Objective Exosomes, membranous nanovesicles, naturally bringing proteins, mRNAs, and microRNAs (miRNAs), play crucial roles in tumor pathogenesis. This study was to investigate the role of miR-155-3p from M2 macrophages-derived exosomes (M2-Exo) in promoting medulloblastoma (MB) progression by mediating WD repeat domain 82 (WDR82). Methods miR-155-3p expression was detected by RT-qPCR. The relationship of miR-155-3p with clinicopathological features of MB patients was analyzed. M2-Exo were isolated and identified by TEM, NTA and Western blot. CCK-8 assay, colony formation assay, flow cytometry, wound healing assay, and Transwell assay were performed to explore the role of miR-155-3p-enriched M2-Exo on the progression of MB cells. Luciferase assay were used to identify the relationship between miR-155-3p and WDR82. The effect of miR-155-3p-enriched M2-Exo on tumorigenesis of MB was confirmed by the xenograft nude mice model. Results miR-155-3p was up-regulated in MB tissues of patients and MB cell lines. High miR-155-3p expression was correlated with the pathological type and molecular subtype classification of MB patients. WDR82 was a direct target of miR-155-3p. miR-155-3p was packaged into M2-Exo. miR-155-3p-enriched M2-Exo promoted the progression of Daoy cells. miR-155-3p-enriched M2-Exo promoted in vivo tumorigenesis. Conclusion The study highlights that miR-155-3p-loaded M2-Exo enhances the growth of MB cells via down-regulating WDR82, which might provide a deep insight into MB mechanism.


1997 ◽  
Vol 185 (6) ◽  
pp. 1065-1076 ◽  
Author(s):  
Robert S. Byrum ◽  
Jennifer L. Goulet ◽  
Richard J. Griffiths ◽  
Beverly H. Koller

Leukotrienes are potent inflammatory mediators synthesized from arachidonic acid (AA) predominately by cells of myeloid origin. The synthesis of these lipids is believed to be dependent not only on the expression of the enzyme 5-lipoxygenase (5-LO), which catalyzes the first steps in the synthesis of leukotrienes, but also on expression of a nuclear membrane protein termed the 5-LO–activating protein (FLAP). To study the relationship of these two proteins in mediating the production of leukotrienes in vivo and to determine whether the membrane protein FLAP has additional functions in various inflammatory processes, we have generated a mouse line deficient in this protein. FLAP-deficient mice develop normally and are healthy. However, an array of assays comparing inflammatory reactions in FLAP-deficient mice and in normal controls revealed that FLAP plays a role in a subset of these reactions. Although examination of DTH and IgE-mediated passive anaphylaxis showed no difference between wild-type and FLAP-deficient animals, mice without FLAP possessed a blunted inflammatory response to topical AA and had increased resistance to platelet-activating factor–induced shock compared to controls. Also, edema associated with Zymosan A–induced peritonitis was markedly reduced in animals lacking FLAP. To determine whether these differences relate solely to a deficit in leukotriene production, or whether they reflect an additional role for FLAP in inflammation, we compared the FLAP-deficient mice to 5-LO–deficient animals. Evaluation of mice lacking FLAP and 5-LO indicated that production of leukotrienes during inflammatory responses is dependent upon the availability of FLAP and did not support additional functions for FLAP beyond its role in leukotriene production.


2020 ◽  
Vol 17 (6) ◽  
pp. 76-91
Author(s):  
E. D. Solozhentsev

The scientific problem of economics “Managing the quality of human life” is formulated on the basis of artificial intelligence, algebra of logic and logical-probabilistic calculus. Managing the quality of human life is represented by managing the processes of his treatment, training and decision making. Events in these processes and the corresponding logical variables relate to the behavior of a person, other persons and infrastructure. The processes of the quality of human life are modeled, analyzed and managed with the participation of the person himself. Scenarios and structural, logical and probabilistic models of managing the quality of human life are given. Special software for quality management is described. The relationship of human quality of life and the digital economy is examined. We consider the role of public opinion in the management of the “bottom” based on the synthesis of many studies on the management of the economics and the state. The bottom management is also feedback from the top management.


2014 ◽  
Vol 4 (2) ◽  
Author(s):  
Tamara Feldman

This paper is a contribution to the growing literature on the role of projective identification in understanding couples' dynamics. Projective identification as a defence is well suited to couples, as intimate partners provide an ideal location to deposit unwanted parts of the self. This paper illustrates how projective identification functions differently depending on the psychological health of the couple. It elucidates how healthier couples use projective identification more as a form of communication, whereas disturbed couples are inclined to employ it to invade and control the other, as captured by Meltzer's concept of "intrusive identification". These different uses of projective identification affect couples' capacities to provide what Bion called "containment". In disturbed couples, partners serve as what Meltzer termed "claustrums" whereby projections are not contained, but imprisoned or entombed in the other. Applying the concept of claustrum helps illuminate common feelings these couples express, such as feeling suffocated, stifled, trapped, held hostage, or feeling as if the relationship is killing them. Finally, this paper presents treatment challenges in working with more disturbed couples.


2019 ◽  
Vol 58 (2) ◽  
pp. 249-259
Author(s):  
Joseph Acquisto

This essay examines a polemic between two Baudelaire critics of the 1930s, Jean Cassou and Benjamin Fondane, which centered on the relationship of poetry to progressive politics and metaphysics. I argue that a return to Baudelaire's poetry can yield insight into what seems like an impasse in Cassou and Fondane. Baudelaire provides the possibility of realigning metaphysics and politics so that poetry has the potential to become the space in which we can begin to think the two of them together, as opposed to seeing them in unresolvable tension. Or rather, the tension that Baudelaire animates between the two allows us a new way of thinking about the role of esthetics in moments of political crisis. We can in some ways see Baudelaire as responding, avant la lettre, to two of his early twentieth-century readers who correctly perceived his work as the space that breathes a new urgency into the questions of how modern poetry relates to the world from which it springs and in which it intervenes.


Author(s):  
Pavel Agapov ◽  
Kirill Stepkin

The article considers the general theoretical foundations of the relationship of sectarianism and religious extremism in the Russian Federation. Practical examples of the role of destructive sects in modern religious extremism in the Russian Federation are given.


2020 ◽  
Vol 63 (4) ◽  
pp. 115-131
Author(s):  
Maria M. Kuznetsova

The article examines the philosophy of Henri Bergson and William James as independent doctrines aimed at rational comprehension of spiritual reality. The doctrines imply the paramount importance of consciousness, the need for continuous spiritual development, the expansion of experience and perception. The study highlights the fundamental role of spiritual energy for individual and universal evolution, which likens these doctrines to the ancient Eastern teaching as well as to Platonism in Western philosophy. The term “spiritual energy” is used by Bergson and James all the way through their creative career, and therefore this concept should considered in the examination of their solution to the most important philosophical and scientific issues, such as the relationship of matter and spirit, consciousness and brain, cognition, free will, etc. The “radical empiricism” of William James and the “creative evolution” of Henry Bergson should be viewed as conceptions that based on peacemaking goals, because they are aimed at reconciling faith and facts, science and religion through the organic synthesis of sensory and spiritual levels of experience. Although there is a number of modern scientific discoveries that were foreseen by philosophical ideas of Bergson and James, both philosophers advocate for the artificial limitation of the sphere of experimental methods in science. They call not to limit ourselves to the usual intellectual schemes of reality comprehension, but attempt to touch the “living” reality, which presupposes an increase in the intensity of attention and will, but finally brings us closer to freedom.


2020 ◽  
Author(s):  
Agnieszka Wykowska ◽  
Jairo Pérez-Osorio ◽  
Stefan Kopp

This booklet is a collection of the position statements accepted for the HRI’20 conference workshop “Social Cognition for HRI: Exploring the relationship between mindreading and social attunement in human-robot interaction” (Wykowska, Perez-Osorio & Kopp, 2020). Unfortunately, due to the rapid unfolding of the novel coronavirus at the beginning of the present year, the conference and consequently our workshop, were canceled. On the light of these events, we decided to put together the positions statements accepted for the workshop. The contributions collected in these pages highlight the role of attribution of mental states to artificial agents in human-robot interaction, and precisely the quality and presence of social attunement mechanisms that are known to make human interaction smooth, efficient, and robust. These papers also accentuate the importance of the multidisciplinary approach to advance the understanding of the factors and the consequences of social interactions with artificial agents.


2020 ◽  
Vol 2 (4) ◽  
pp. 126-130
Author(s):  
N. V. SHAMANIN ◽  

The article raises the issue of the relationship of parent-child relationships and professional preferences in pedagogical dynasties. Particular attention is paid to the role of the family in the professional development of the individual. It has been suggested that there is a relationship between parent-child relationships and professional preferences.


Author(s):  
Dan Honig

This chapter traces the relationship between political authorizing environments, international development organization (IDO) management, and IDO field agents, drawing on the empirics presented in chapters 6 and 7. It digs into the experience of working for USAID as compared to DFID. It also extends the discussion of delegation to implementing contractors and brings this book’s theorizing of Navigation by Judgment into conversation with other foreign aid solutions aimed at incorporating local knowledge, such as establishing country offices or ensuring projects have country ownership. This chapter connects Part II’s empirics more tightly to the mechanisms theorized in Part I , particularly the role of authorizing environment insecurity and the need to “manage up” (Chapter 4) and their implications for the workplace experience of agents (Chapter 3) and the entry and exit of personnel.


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