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関連する概念動画

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
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Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
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Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

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As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
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Ribosome Profiling02:24

Ribosome Profiling

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Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
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Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
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狼の確立と悪化を裏付ける異なったトランスクリプトーム構造

Masahiro Nakano1, Mineto Ota2, Yusuke Takeshima3

  • 1Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo 113-0033, Japan; Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.

Cell
|August 23, 2022
PubMed
まとめ

この研究により,全身性白血病 (SLE) 免疫細胞における異なった遺伝子発現パターンが明らかになり,疾患の状態と活性が区別される. これらの発見は,SLEの病原性および潜在的な治療目標に関する新しい洞察を提供します.

キーワード:
東京大学からの免疫細胞遺伝子表現アトラス細胞タイプ別病気の活動病気状態免疫細胞免疫遺伝学臓器の関与全身性赤血性狼治療効果トランスクリプトーム

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The bm12 Inducible Model of Systemic Lupus Erythematosus SLE in C57BL/6 Mice
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Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
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The bm12 Inducible Model of Systemic Lupus Erythematosus SLE in C57BL/6 Mice
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科学分野:

  • 免疫学
  • ゲノミクス
  • コンピュータ生物学

背景:

  • システミック・ルプス・エリテマトーサス (SLE) は,多系統的炎症を特徴とする複雑な自己免疫疾患である.
  • 有効な治療法の開発には,SLEの病原性に基づく細胞および分子メカニズムを理解することが重要です.
  • SLE患者における遺伝子発現パターンは,異なる免疫細胞タイプによって有意に異なります.

研究 の 目的:

  • 高細胞解像度で遺伝子発現パターンを分析することによって,SLEの病原性を解明する.
  • SLE 疾患の状態と活動に関連した細胞型特異のトランスクリプトミカルシグネチャを特定する.
  • これらのシグネチャーの臨床的関連性とその遺伝的危険因子との関係を調査する.

主な方法:

  • 6,386のRNAシーケンシングデータセットを用いた大規模なトランスクリプトーム解析を行った.
  • 136人のSLE患者と89人の健康なドナーの27種類の免疫細胞を対象とした.
  • 疾患状態と疾患活動シグネチャーをプロファイルし,SLEリスク変異体による濃縮を分析した.

主要な成果:

  • 2つの異なる細胞型特異のトランスクリプトミカルシグネチャーを特定しました. 病状と病状活性です.
  • SLEにおける臓器関わりと治療反応と相関する疾患活性シグネチャー.
  • 疾患状態シグネチャーは,疾患活動シグネチャと比較して,SLEリスクの変種をめぐってより高い濃縮を示した.

結論:

  • SLE のための包括的な遺伝子シグネチャが特定され,将来の研究のための基礎データを提供しました.
  • SLEの進行と治療の有効性を評価するために,疾患活動シグネチャーは臨床的価値を持っています.
  • 現在の遺伝学的な研究は,SLEの臨床的に重要な生物学を完全に捉えることはできません.