1,721,155 research outputs found
Palmitate reduces starvation-induced ER stress by inhibiting ER-phagy in hypothalamic cells
Palmitate is a saturated fatty acid that is well known to induce endoplasmic reticulum (ER) stress and autophagy. A high-fat diet increases the palmitate level in the hypothalamus, the main region of the brain regulating energy metabolism. Interestingly, hypothalamic palmitate level is also increased under starvation, urging the study to distinguish the effects of elevated hypothalamic palmitate level under different nutrient conditions. Herein, we show that ER-phagy (ER-targeted selective autophagy) is required for progress of ER stress and that palmitate decreases ER stress by inhibiting ER-phagy in hypothalamic cells under starvation. Palmitate inhibited starvation-induced ER-phagy by increasing the level of B-cell lymphoma 2 (Bcl-2) protein, which inhibits autophagy initiation. These findings suggest that, unlike the induction of ER stress under nutrient-rich conditions, palmitate protects hypothalamic cells from starvation-induced stress by inhibiting ER-phagy. © 2021, The Author(s).1
레이저표면용융된 니켈기 합금 600의 미세구조와 부식특성에 관한 연구
학위논문(박사) - 한국과학기술원 : 재료공학과, 2000.2, [ vi, 168 p. ]Surface melting by a continuous laser beam was performed on the Ni-base Alloy 600 (or Alloy 600), which has been used as a steam generator tubing material. The microstructural changes of the laser treated Alloy 600 were investigated with various microscopic equipments including a scanning electron microscope and a (scanning) transmission microscope equipped with energy dispersive X-ray spectroscopy. The susceptibility to intergranular corrosion of the laser treated Alloy 600 was evaluated from the results of the C-ring and DL-EPR tests.
By laser surface melting (LSM) on the sensitized Alloy 600, the Cr-rich carbides having precipitated along the grain boundaries during sensitization treatments were dissolved completely or partially in the heat affected zone (HAZ), close to or far from the laser melted zone (LMZ), respectively. At the same time, the disappearance of Cr depletion at the boundaries were accompanied (i.e., de-sensitization occurred). The microstructure of the LMZ, having epitaxially solidified from the HAZ, consisted of a very narrow plane front solidification region and a cellular solidification region with fine cellular-dendrites in the grains. Chromium was enriched along the cell boundaries in the LMZ due to the microsegregation during solidification. In addition, very fine particles were distributed along the cell boundaries with tangled dislocations around them. The solidification behavior in the LSM Alloy 600 was analysed with respect to the laser treatment conditions employed in the present study.
Most of the tiny particles in the cellular-dendritically solidified regions of the LMZ were identified as TiN type particles. Another type of particle, MgS was also found as being attached on the TiN type particles. The tiny particles were located along the cell boundaries in the cellular-dendritic structure, but not observed in the regions solidified by a plane front mode in the LMZ. The number density of TiN type particles was measured to...한국과학기술원 : 재료공학과
Comparative metabolic profiling of posterior parietal cortex, amygdala, and hippocampus in conditioned fear memory
Fear conditioning and retrieval are suitable models to investigate the biological basis of various mental disorders. Hippocampus and amygdala neurons consolidate conditioned stimulus (CS)-dependent fear memory. Posterior parietal cortex is considered important for the CS-dependent conditioning and retrieval of fear memory. Metabolomic screening among functionally related brain areas provides molecular signatures and biomarkers to improve the treatment of psychopathologies. Herein, we analyzed and compared changes of metabolites in the hippocampus, amygdala, and posterior parietal cortex under the fear retrieval condition. Metabolite profiles of posterior parietal cortex and amygdala were similarly changed after fear memory retrieval. While the retrieval of fear memory perturbed various metabolic pathways, most metabolic pathways that overlapped among the three brain regions had high ranks in the enrichment analysis of posterior parietal cortex. In posterior parietal cortex, the most perturbed pathways were pantothenate and CoA biosynthesis, purine metabolism, glutathione metabolism, and NAD+ dependent signaling. Metabolites of posterior parietal cortex including 4′-phosphopantetheine, xanthine, glutathione, ADP-ribose, ADP-ribose 2′-phosphate, and cyclic ADP-ribose were significantly regulated in these metabolic pathways. These results point to the importance of metabolites of posterior parietal cortex in conditioned fear memory retrieval and may provide potential biomarker candidates for traumatic memory-related mental disorders. © 2021, The Author(s).1
팔미테이트가 시상하부 세포에서의 자가포식작용과 소포체 스트레스 조절에 미치는 역할
Palmitate, Autophagy, ER-phagy, ER stress, HypothalamusPalmitate is a saturated fatty acid that is well known to induce endoplasmic reticulum (ER) stress and autophagy. A high-fat diet (HFD) increases the palmitate level in the hypothalamus, the main region of the brain regulating energy metabolism, and induces lipotoxic inflammation related to obesity and type 2 diabetes mellitus. Interestingly, hypothalamic palmitate level is also increased under starvation, demanding the study to distinguish the effects of elevated hypothalamic palmitate level under different nutrient conditions. Herein, I show that ER-phagy (ER-targeted selective autophagy) is an antecedent to ER stress and that palmitate decreases ER stress by inhibiting ER-phagy in hypothalamic cells under starvation conditions. Palmitate inhibited starvation-induced ER-phagy by increasing the level of B-cell lymphoma 2 (Bcl-2) protein, which inhibits autophagy initiation. These findings suggest that palmitate, unlike increases ER stress under nutrient-rich conditions, decreases ER stress in hypothalamic cells by inhibiting ER-phagy under starvation conditions.
|팔미테이트(palmitate)는 대표적인 포화지방산 중 하나로서 여러 세포에서 소포체 스트레스(ER stress)와 자가포식작용(autophagy)을 일으키는 것으로 잘 알려져있다. 지속적인 고지방 식이는 시상하부의 지방산 농도를 올리고, 이는 비만이나 대사장애로 이어진다. 흥미롭게도 팔미테이트를 포함한 지방산 농도는 굶주린 상태에서도 올라가는데 이 때 올라간 지방산은 여러 신체 부위에서 주로 연료로 쓰이나, 뇌 특히 시상하부에서 어떤 역할을 하는지에 대해서는 연구가 거의 되지 않았다. 본 논문에서는 시상하부 세포에 그냥 팔미테이트를 처리했을 때와 기아 조건(starvation)을 준 뒤 팔미테이트를 처리했을 때 각각 팔미테이트가 소포체 스트레스와 자가포식에 어떤 영향을 미치는지를 연구하였다. 시상하부 세포에 팔미테이트를 처리하면 소포체 스트레스와 자가포식작용이 일어나지만 팔미테이트 처리시간이 길어지면 자가포식작용이 망가지는 것을 확인하였다. 시상하부 세포를 기아 상태로 만들면 소포체를 타겟으로 한 자가포식, 즉 소포체자가포식(ER-phagy)이 일어나고 이 소포체자가포식은 소포체 스트레스에 선행된다. 놀랍게도 시상하부 세포를 굶길 때 팔미테이트를 함께 처리하면 기아로 인해 일어나던 소포체자가포식이 자가포식의 시작 단계인 자가포식체(autophagosome)형성 단계부터 저해되어 자가포식체 개수가 현저히 감소되었다. 소포체자가포식이 감소하였기 때문에 소포체자가포식 뒤에 일어나던 소포체 스트레스 또한 함께 감소하는 것을 확인하였고, 이 과정에서 항자가포식인자 중 하나인 Bcl-2라는 단백질이 증가하는 것을 관찰하였다. 넉다운(knockdown)실험을 통해 Bcl-2 양을 감소시켰을 때 팔미테이트가 기아로 인해 일어난 소포체자가포식을 막는 정도가 줄어들었고, 이에 따라 Bcl-2가 팔미테이트가 기아로 인한 소포체자가포식을 줄이는 데에 중추적인 역할을 한다는 것이 증명되었다. 팔미테이트 처리 혹은 굶주림 조건이 각각 단독으로는 소포체 스트레스를 올리는 사실에 비추어보았을 때, 이 두 조건을 함께 처리하였을 때 소포체 스트레스가 줄어든다는 것은 팔미테이트가 기아 상태라는 특정한 상황에서는 소포체 스트레스를 다르게 조절할 수 있다는 가능성을 시사한다. 영양 결핍 상태의 시상하부 세포에서 팔미테이트가 소포체자가포식과 소포체 스트레스를 줄이는 효과를 증명한 본 연구가 앞으로 시상하부 세포의 소포체자가포식 연구에 도움이 되기를 기대한다.YAbstract ⅰ
List of contents ⅱ
List of tables ⅳ
List of figures ⅴ
List of abbreviations ⅶ
Ⅰ. Introduction 1
1. Hypothalamus 1
2. Palmitate 1
2.1 Regulation of palmitate in high-fat diet 1
2.2 Regulation of palmitate under starvation 2
3. ER stress 4
4. Autophagy 6
4.1 Macroautophagy 6
4.2 Selective autophagy: ER-phagy 9
5. Aims of the study 11
Ⅱ. Materials and methods 12
1. Cell culture 12
2. Preparation of palmitate 12
3. siRNA and plasmid transfection 12
4. Immunocytochemistry 13
5. Antibodies and chemical reagents 13
6. Western blotting 14
7. RNA extraction and quantitative Real time-PCR 15
8. Statistical analysis 15
Ⅲ. Results 17
1. Palmitate induces ER stress 17
2. Palmitate induces autophagy in a short time treatment but the prolonged treatment of palmitate impairs autophagy 20
3. Palmitate impairs ER-phagy at the autophagosome maturation step 23
4. Palmitate does not induce mitophagy 26
5. Short-term treatment with palmitate inhibits ER-phagy under starvation 29
6. ER-phagy precedes ER stress and palmitate reduces ER stress by inhibiting ER-phagy under starvation 33
7. Palmitate inhibits ER-phagy at the initiation step under starvation 37
8. Inhibition of Bcl-2 ameliorates the inhibitory effect of palmitate on ER-phagy under starvation 41
Ⅳ. Discussion 46
Ⅴ. Conclusion 51
Ⅵ. References 52
Abstract in Korean 62DoctordCollectio
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
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Robust Execution Strategy for Scheduling Under Uncertainity
VARAKANTHAM, Pradeep; CHENG, Shih-Fen ; LIM, Yun Fong</p
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
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