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Defining the let-7 microRNA-mediated molecular mechanisms regulating T cell differentiation
CD4+ and CD8+ T cells are lymphocytes of the adaptive immune system that play essential roles in immunity. Both T cell subsets recognize their cognate antigen through the T cell receptor (TCR), which induces the proliferation and differentiation of these antigen-specific cells into effector T cells. CD4+ T cells have the potential to differentiate into one of multiple lineages of helper T (Th) cells and participate indirectly in antigen clearance by orchestrating the function of other cells. CD8+ T cells differentiate into cytotoxic T lymphocytes (CTL), which directly contributes to the resolution of an infection by killing cancerous or virally-infected cells. Upon antigen clearance, most effector T cells die, but some survive and generate long-lived memory T cells that will respond faster and more efficiently to subsequent encounters with the same antigen. When antigen fails to be cleared, such as in chronic infections and cancer, effector T cells are diverted into a hyporesponsive state, exhaustion, characterized by the upregulation of co-inhibitory receptors that transmits inhibitory signals resulting in the loss of effector function and memory potential. Moreover, when T cell differentiation is dysregulated, T cell responses become aberrant, causing autoimmune diseases. Therefore, understanding the molecular mechanisms controlling T cell responses is important to develop innovative treatments that can enhance T cell activity during infections and cancer, and dampen the generation of disease-causing T cells in autoimmunity. We have uncovered a novel post-transcriptional mechanism regulating T cell differentiation. Particularly, we showed that the let-7 family of miRNAs is highly expressed in naive T cells, but gets dramatically downregulated upon antigen encounter, proportionally to both the strength and duration of TCR stimulation. Specifically, let-7 downregulation was required for the differentiation of pathogenic Th17 cells in experimental autoimmune encephalomyelitis (EAE), a mouse model of the autoimmune disease multiple sclerosis (MS). In CD8+ T cells, although let-7 inhibits CTL differentiation in vitro, let-7 was demonstrated both in silico and in vivo to promote memory CD8+ T cell formation, while repressing the differentiation of terminal effectors, which are susceptible to exhaustion. Thus, let-7 constitutes a promising tool for the therapeutic manipulation of T cell responses
[Review of] Luvenia A. George. Teaching the Music of Six Different Cultures
With the recent appearance of more authentic ethnic music in music curriculum series, as well as the spreading influence of the Orff approach to music education based on indigenous and primitive musics and even the proliferation of commercial music influenced by non-Western styles, the appetite of music teachers has been well-whetted for additional source material on ethnic music. In this revised edition of Luvenia George\u27s 1976 book, we have an extraordinary resource that now makes it inexcusable not to have an enriched music program in our schools
Analysis of the Caddisflies (Trichoptera) of the Manistee River Watershed, Michigan
We document 134 caddisfly species and their seasonal and habitat affinities based on 93 samples collected from 26 sites throughout the Manistee River watershed in the lower peninsula of Michigan from May through September, 2010. Eleven of these species: Banksiola dossuaria (Say), Cheumatopsyche aphanta Ross, Cheumatopsyche pasella Ross, Hydroptila xera Ross, Ironoquia lyrata (Ross), Lepidostoma vernale (Banks), Neotrichia vibrans Ross, Nyctiophylax affinis (Banks), Oxyethira aeola Ross, Oxyethira rivicola Blickle and Morse, and Polycentropus timesis (Denning) are reported from Michigan for the first time. More than 85% of species reached peak adult abundance during June or July, although a few species reached peak abundance or emerged exclusively during the other months. Overall species richness reached its peak during early July, with a smaller peak of unique species in September. Caddisfly faunas in lakes, small streams, medium rivers, and large rivers were all distinct from each other, suggesting that the overall watershed is following patterns predicted by the River Continuum Concept. It is likely that the Michigan caddisfly fauna contains considerably more species than what is currently known
The patient's role in the family: comparison of task performance as perceived by discharged and readmitted patients and their marital partners
Thesis (M.S.)--Boston Universit
低圧水バイナリ温泉発電に関する研究
東京海洋大学修士学位論文 平成30年度(2018) 海洋システム工学 第3101号指導教員: 堀木幸代全文公表年月日: 2019-05-16東京海洋大学201
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