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関連する概念動画

RNA Editing02:23

RNA Editing

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RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
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Locus of Control01:26

Locus of Control

220
Locus of control describes how individuals perceive the causes of events in their lives, influencing motivation and well-being. Introduced by Julian Rotter in 1954, it is categorized into internal and external locus of control.Internal Locus of ControlIndividuals with an internal locus of control believe their actions determine outcomes, fostering responsibility, self-efficacy, and motivation. For example, an employee may attribute career success to hard work. Research links this mindset to...
220
Root-Locus Method01:19

Root-Locus Method

515
A cruise control system in a car is designed to maintain a specified speed automatically by adjusting the gas pedal. The system continuously measures the vehicle's speed and makes fine adjustments to the pedal to achieve this goal. The root locus method is particularly useful for understanding how the cruise control system's behavior changes under varying conditions, such as when the car goes uphill, downhill, or faces strong wind resistance.
This system can be represented by a block...
515
Construction of Root Locus01:15

Construction of Root Locus

421
The construction of a root locus involves several key steps to analyze and visualize the behavior of a system's poles with varying gain. The number of branches in the root locus equals the number of closed-loop poles and is symmetrical about the real axis.
For positive gain values, the root locus exists on the real axis to the left of an odd number of finite open-loop poles or zeros. The root locus starts at the open-loop poles and traces the paths of the closed-loop poles as the gain...
421
Properties of the Root Locus01:05

Properties of the Root Locus

307
The root locus method is an invaluable tool for analyzing higher-order systems without needing to factor the denominator of the transfer function. A pole of the system is identified when the characteristic polynomial in the transfer function's denominator equals zero.
To determine if a point lies on the root locus, the criterion involves the sum of angles contributed by all poles and zeros to that point. Specifically, this sum must be an odd multiple of 180 degrees. The gain at any point on...
307
Rotter's Locus of Control01:14

Rotter's Locus of Control

945
Julian Rotter introduced the concept of locus of control, a cognitive factor that significantly influences personality development and learning. Locus of control refers to an individual's beliefs about the extent of control they have over events in their lives. According to Rotter, this belief system can be categorized into two types: internal and external locus of control.
Individuals with an internal locus of control believe that their personal efforts and decisions directly affect their...
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Fundus Photography as a Convenient Tool to Study Microvascular Responses to Cardiovascular Disease Risk Factors in Epidemiological Studies
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ハプロタイプ編集により,最も影響力のある心血管リスクロクスの役割を明らかにする

Valentina Lo Sardo1, Pavel Chubukov1, William Ferguson1

  • 1Department of Neuroscience, The Scripps Research Institute, La Jolla, CA 92037, USA.

Cell
|December 12, 2018
PubMed
まとめ
この要約は機械生成です。

9p21. 3遺伝子は冠動脈疾患 (CAD) のリスクを大幅に増加させる. この研究は,特定のDNAセグメントであるリスクハプロタイプが,血管滑らかな筋肉細胞 (VSMC) の機能を変化させ,CADの発達に貢献することを明らかにしています.

キーワード:
動脈壁心血管疾患冠動脈病気モデリングゲノム編集iPSC についてlncRNA について幹細胞血管の滑らかな筋肉細胞

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科学分野:

  • 遺伝学
  • 心血管生物学
  • 幹細胞生物学

背景:

  • 9p21.3は冠動脈疾患 (CAD) の主要な遺伝的危険因子であり,特に非アフリカ人集団ではそうである.
  • このリスクは,約60kbの非コーディングDNAセグメント (ハプロタイプ) と関連しており,その機能は不明である.
  • この場所がCADに影響を与えるメカニズムを理解することは,標的治療の開発に不可欠です.

研究 の 目的:

  • 血管の滑らかな筋肉細胞 (VSMC) での9p21.3リスクハプロタイプの機能的役割を調査する.
  • 9p21.3ロカスと冠動脈疾患の関連性を明らかにする.
  • ヒトゲノムの機能的なアノテーションのための細胞モデルを確立する.

主な方法:

  • CADリスクハプロタイプ9p21. 3を有する個体から誘発性多能幹細胞 (iPSC) の生成.
  • IPSCのリスクハプロタイプを削除するゲノム編集
  • 血管の滑らかな筋肉細胞 (VSMC) に iPSC の分化.
  • VSMCの転写プロファイリングと機能分析 (粘着,収縮,増殖)

主要な成果:

  • リスクハプロタイプから派生したVSMCは,既知のCADリスク遺伝子と経路に影響を与える,転写ネットワークの広範な変化を示した.
  • これらのリスクのVSMCは異常な粘着,収縮,増殖を示した.
  • リスクハプロタイプを削除するとVSMCの安定性が回復し,非リスクのVSMCでは長い非コーディングRNAANRILの発現が誘発された.

結論:

  • 9p21. 3のリスクハプロタイプは,VSMCをCAD現象型に関連した細胞状態に誘導する.
  • この研究では,CADリスクに関与する新しいVSMCベースの遺伝子ネットワークを特定しました.
  • ハプロタイプ編集されたiPSCは,機能的なゲノムアノテーションと複雑な疾患の遺伝学を理解するための貴重なツールとして機能します.