scholarly journals Direct and essential function for Hrd3 in ER-associated degradation

2016 ◽  
Vol 113 (21) ◽  
pp. 5934-5939 ◽  
Author(s):  
Nidhi Vashistha ◽  
Sonya E. Neal ◽  
Amanjot Singh ◽  
Sarah M. Carroll ◽  
Randolph Y. Hampton
Keyword(s):  
Critical Role ◽  
Stability Loss ◽  
Degradation Pathway ◽  
Living Cells ◽  
Significant Loss ◽  
New Approach ◽  
The Core ◽  
Essential Function ◽  
Coa Reductase ◽  
Stoichiometric Complex

The HRD (HMG-CoA reductase degradation) pathway is a conserved route of endoplasmic reticulum-associated degradation (ERAD), by which misfolded ER proteins are ubiquitinated and degraded. ERAD substrates are ubiquitinated by the action of the Hrd1 RING-H2 E3 ligase. Hrd1 is always present in a stoichiometric complex with the ER membrane protein Hrd3, which is also required for HRD-dependent degradation. Despite its conserved presence, unequivocal study of Hrd3 function has been precluded by its central role in Hrd1 stability. Loss of Hrd3 causes unrestricted self-degradation of Hrd1, resulting in significant loss of the core ligase. Accordingly, the degree to which Hrd3 functions independently of Hrd1 stabilization has remained unresolved. By capitalizing on our studies of Usa1 in Hrd1 degradation, we have devised a new approach to evaluate Hrd3 functions in ERAD. We now show that Hrd3 has a direct and critical role in ERAD in addition to Hrd1 stabilization. This direct component of Hrd3 is phenotypically as important as Hrd1 in the native HRD complex. Hrd3 was required the E3 activity of Hrd1, rather than substrate or E2 recruitment to Hrd1. Although Hrd1 can function in some circumstances independent of Hrd3, these studies show an indispensable role for Hrd3 in living cells.

Evaluation on the performance fluctuation after water ingestion for a turbofan engine compressor during flight descent

2020 ◽  
pp. 095441002097798
Author(s):  
Lu Yang ◽  
Qun Zheng ◽  
Aqiang Lin
Keyword(s):  
Droplet Diameter ◽  
Pressure Ratio ◽  
Critical Role ◽  
Water Film ◽  
Heavy Rain ◽  
Diameter Distribution ◽  
Turbofan Engine ◽  
Water Ingestion ◽  
The Core ◽  
Engine Compressor

Turbofan engine compressor is most severely threatened by the entry of liquid water during flight descent. This study aims to deeply understand the fluctuations of compressor performance parameters caused by water ingestion through frequency spectrum analysis. The water content and droplet diameter distribution are determined based on the real heavy rain environment. Results reveal that most of the droplets actually entering the core compressor have a particle size of less than 100 μm. In addition, the formation and motion of water film plays a critical role in affecting the fluctuation characteristics. Water ingestion deteriorates the compression performance and aggravates the unsteady fluctuations of the fan. However, the performance of the core compressor is less affected by water ingestion, but their fluctuations are still exacerbated. For some important parameters, such as inlet mass flow rate, total pressure ratio, total temperature ratio, compression work and efficiency, their main frequency of fluctuation are switched from the original blade passing frequency to the rotor passing frequency, and their amplitudes are correspondingly amplified to varying degrees. These phenomena can be observed in both the fluctuations of the fan and core compressor. Moreover, the operating point of them will be in the long-period and large-amplitude fluctuations, which leads them experiences the non-optimal state for a long time and threatens their operating stability.

scholarly journals Cell cycle–dependent localization of macroH2A in chromatin of the inactive X chromosome

2002 ◽  
Vol 157 (7) ◽  
pp. 1113-1123 ◽  
Author(s):  
Brian P. Chadwick ◽  
Huntington F. Willard
Keyword(s):  
Cell Cycle ◽  
X Chromosome ◽  
Degradation Pathway ◽  
S Phase ◽  
Histone H2a ◽  
The Core ◽  
Inactive X Chromosome ◽  
Inactivation Center ◽  
Chromatin Proteins ◽  
Cycle Dependent

One of several features acquired by chromatin of the inactive X chromosome (Xi) is enrichment for the core histone H2A variant macroH2A within a distinct nuclear structure referred to as a macrochromatin body (MCB). In addition to localizing to the MCB, macroH2A accumulates at a perinuclear structure centered at the centrosome. To better understand the association of macroH2A1 with the centrosome and the formation of an MCB, we investigated the distribution of macroH2A1 throughout the somatic cell cycle. Unlike Xi-specific RNA, which associates with the Xi throughout interphase, the appearance of an MCB is predominantly a feature of S phase. Although the MCB dissipates during late S phase and G2 before reforming in late G1, macroH2A1 remains associated during mitosis with specific regions of the Xi, including at the X inactivation center. This association yields a distinct macroH2A banding pattern that overlaps with the site of histone H3 lysine-4 methylation centered at the DXZ4 locus in Xq24. The centrosomal pool of macroH2A1 accumulates in the presence of an inhibitor of the 20S proteasome. Therefore, targeting of macroH2A1 to the centrosome is likely part of a degradation pathway, a mechanism common to a variety of other chromatin proteins.

Revising the Assumption that Ḥadīṯ Studies Flourished in the 11th/17th-Century Ḥiǧāz: Ibrāhīm al-Kūrānī’s (d. 1101/1690) Contribution

Arabica ◽  
2021 ◽  
Vol 68 (1) ◽  
pp. 1-35
Author(s):  
Naser Dumairieh
Keyword(s):  
General Framework ◽  
18Th Century ◽  
Critical Role ◽  
17Th Century ◽  
Main Interest ◽  
Islamic World ◽  
The Core ◽  
Revival Movement ◽  
Almost All

Abstract The Ḥiǧāz in the 11th/17th century has long been considered the center of a “revival” movement in ḥadīṯ studies. This assumption has spread widely among scholars of the 11th-/17th- and 12th-/18th-century Islamic world based on the fact that the isnāds of many major ḥadīṯ scholars from almost all parts of the Islamic world from the 11th/17th century onward return to a group of scholars in the Ḥiǧāz. The scholarly group that is assumed to have played a critical role in the flourishing of ḥadīṯ studies in the 11th/17th-century Ḥiǧāz is called the al-Ḥaramayn circle or network. However, to date, there have been no studies that investigate what was actually happening in that century concerning ḥadīṯ studies. Examining the actual ḥadīṯ studies of one of the scholars at the core of al-Ḥaramayn circle, i.e. Ibrāhīm b. Ḥasan al-Kūrānī, will unpack the main interest of Ḥiǧāzī scholars in ḥadīṯ literature, reveal previously unstudied aspects of ḥadīṯ studies in the 11th/17th-century Ḥiǧāz, correct some unexamined assumptions, and situate the ḥadīṯ efforts of scholars of the 11th/17th-century Ḥiǧāz within a general framework of developments within ḥadīṯ studies.

scholarly journals In Vitro and in Vivo Imaging of Nitroxyl with Copper Fluorescent Probe in Living Cells and Zebrafish

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2551 ◽  
Author(s):  
Sathyadevi Palanisamy ◽  
Yu-Liang Wang ◽  
Yu-Jen Chen ◽  
Chiao-Yun Chen ◽  
Fu-Te Tsai ◽  
...  
Keyword(s):  
Critical Role ◽  
Model Organism ◽  
Living Cells ◽  
Biological Species ◽  
Zebrafish Model ◽  
Physiological Processes ◽  
Collective Data ◽  
Angeli's Salt

Nitroxyl (HNO) plays a critical role in many physiological processes which includes vasorelaxation in heart failure, neuroregulation, and myocardial contractility. Powerful imaging tools are required to obtain information for understanding the mechanisms involved in these in vivo processes. In order to develop a rapid and high sensitive probe for HNO detection in living cells and the zebrafish model organism, 2-((2-(benzothiazole-2yl)benzylidene) amino)benzoic acid (AbTCA) as a ligand, and its corresponding copper(II) complex Cu(II)-AbTCA were synthesized. The reaction results of Cu(II)-AbTCA with Angeli’s salt showed that Cu(II)-AbTCA could detect HNO quantitatively in a range of 40–360 µM with a detection limit of 9.05 µM. Furthermore, Cu(II)-AbTCA is more selective towards HNO over other biological species including thiols, reactive nitrogen, and reactive oxygen species. Importantly, Cu(II)-AbTCA was successfully applied to detect HNO in living cells and zebrafish. The collective data reveals that Cu(II)-AbTCA could be used as a potential probe for HNO detection in living systems.

scholarly journals Disability and ICF Core Sets in Mood Disorders

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
J.L. Ayuso-Mateos
Keyword(s):  
Mood Disorders ◽  
Significant Loss ◽  
Consensus Conference ◽  
The Body ◽  
The Core ◽  
Core Sets ◽  
Biopsychosocial Perspective ◽  
Icf Core Sets ◽  
Different Levels

The concept of disability has changed enormously, from a notion of handicap (ICIDM,1980) to the idea of person with disability (ICF,2001). The ICF considers three different levels of disability: body, person and environment, offering a possibility to address it in a universal, integrative and interactive perspective. The utility of the ICF in shifting the attention from a medical to a biopsychosocial perspective is therefore accepted. Having 1464 categories, it is hardly applicable to clinical practice and research. Mood disorders are characterized by a variety of psychiatric and somatic symptoms, associated with a significant loss of quality of life and functioning. Practical tools, such as Core Sets, that cover the spectrum of problems are needed. ICF Core Sets have been developed for depression and are currently being developed by our group for bipolar disorder. The ICF Comprehensive Core Sets for depression is the second larger among 12 Comprehensive ICF Core Sets for chronic disorders. This fact reflects the complex limitations in functioning and the numerous interactions with environmental factors. From the first version of the ICF Core Sets for depression as well as the preliminary studies for the bipolar disorder's core sets mental functions are mostly represented among the body functions domain. Few aspects important to mood disorders, as suicide, have been found to be relevant from both a systematic literature review and an expert survey in BD and in the consensus conference were the Core Sets for depression were establish but are not covered in the ICF.

The Dialectics of Resistance: Colonial Geography, Bengali Literati and the Racial Mapping of Indian Identity

2009 ◽  
Vol 44 (1) ◽  
pp. 53-79 ◽  
Author(s):  
SUBHO BASU
Keyword(s):  
Nineteenth Century ◽  
Information System ◽  
Geographic Information System ◽  
Critical Role ◽  
Geographic Information ◽  
Indian Society ◽  
Nation State ◽  
Colonial India ◽  
The Core ◽  
Indian Identity

AbstractThrough a study of hitherto unexplored geography textbooks written in Bengali between 1845 and 1880, this paper traces the evolution of a geographic information system related to ethnicity, race, and space. This geographic information system impacted the mentality of emerging educated elites in colonial India who studied in the newly established colonial schools and played a critical role in developing and articulating ideas of the territorial nation-state and the rights of citizenship in India. The Bengali Hindu literati believed that the higher location of India in such a constructed hierarchy of civilizations could strengthen their claims to rights of citizenship and self-government. These nineteenth century geography textbooks asserted clearly that high caste Hindus constituted the core ethnicity of colonial Indian society and all others were resident outsiders. This knowledge system, rooted in geography/ethnicity/race/space, and related to the hierarchy of civilizations, informed the Bengali intelligentsia's notion of core ethnicity in the future nation-state in India with Hindu elites at its ethnic core.

scholarly journals Inhibition of Vascular Nitric Oxide after Rat Chronic Brain Hypoperfusion: Spatial Memory and Immunocytochemical Changes

2005 ◽  
Vol 25 (6) ◽  
pp. 663-672 ◽  
Author(s):  
Jack C. de la Torre ◽  
Gjumrakch Aliev
Keyword(s):  
Nitric Oxide ◽  
Spatial Memory ◽  
Memory Function ◽  
Critical Role ◽  
Artery Occlusion ◽  
Carotid Artery Occlusion ◽  
Significant Loss ◽  
Electron Microscopic ◽  
Vessel Occlusion ◽  
Common Carotid Artery Occlusion

An aging rat model of chronic brain hypoperfusion (CBH) that mimics human mild cognitive impairment (MCI) was used to examine the role of nitric oxide synthase (NOS) isoforms on spatial memory function. Rats with CBH underwent bilateral common carotid artery occlusion (2-vessel occlusion (2-VO)) for either 26 or 8 weeks and were compared with nonoccluded sham controls (S-VO). The neuronal and endothelial (nNOS/eNOS) constitutive inhibitor nitro-L-arginine methyl ester (L-NAME) 20 mg/kg was administered after 26 weeks for 3 days to 2-VO and S-VO groups and spatial memory was assessed with a modified Morris watermaze test. Only 2-VO rats worsened their spatial memory ability after L-NAME. Electron microscopic immunocytochemical examination using an antibody against eNOS showed 2-VO rats had significant loss or absence of eNOS-containing positive gold particles in hippocampal endothelium and these changes were associated with endothelial cell compression, mitochondrial damage and heavy amyloid deposition in hippocampal capillaries and perivascular region. In the 8-week study, three groups of 2-VO rats were administered an acute dose of 7-NI, aminoguanidine or L-NIO, the relatively selective inhibitors of nNOS, inducible NOS and eNOS. Only rats administered the eNOS inhibitor L-NIO worsened markedly their watermaze performance ( P=0.009) when compared with S-VO nonoccluded controls. We conclude from these findings that vascular nitric oxide derived from eNOS may play a critical role in spatial memory function during CBH possibly by keeping cerebral perfusion optimal through its regulation of microvessel tone and cerebral blood flow and that disruption of this mechanism can result in spatial memory impairment. These findings may identify therapeutic targets for preventing MCI and treating Alzheimer's disease.

scholarly journals Gravitational differentiation in the regimes from stokes settling to Rayleigh–Raylor flows

2019 ◽  
pp. 15-30
Author(s):  
V. P. Trubitsyn
Keyword(s):  
Viscous Fluid ◽  
Interacting Particles ◽  
Small Particles ◽  
Continuous Transition ◽  
New Approach ◽  
Earth's Core ◽  
The Core ◽  
The Earth ◽  
Large Particles ◽  
Two Component

The Earth’s core was formed under gravitational differentiation in the course of the separation of iron and silicates. Most of the iron has gone into the core as early as when the Earth was growing. However, iron continued to precipitate even during the subsequent partial solidification which developed from the bottom upwards. At the different stages and in the different layers of the mantle, iron was deposited in different regimes. In this paper, the mechanisms of the deposition of a cloud of heavy interacting particles (or drops) in a viscous fluid are considered. A new approach suitable for analytical and numerical tracing the changes in the structure of the flows in a two-component suspension under continuous transition from the Stokessettling (for the case of a cloud of large particles) to the Rayleigh–Taylor flows and heavy diapirs (for the case of a cloud of small particles) is suggested. It is numerically and analytically shown that the both regimes are the different limiting cases of the sedimentation convection in suspensions.

scholarly journals THE FUNCTION OF INFORMAL GUANXI CIRCLE IN ANCIENT CHINA POLITICAL STRUCTURE

2017 ◽  
Vol 5 (3) ◽  
pp. 80-87
Author(s):  
Ruihui Han
Keyword(s):  
Common Sense ◽  
Political Power ◽  
Critical Role ◽  
The Political ◽  
Ancient China ◽  
Political Structure ◽  
Previous Researcher ◽  
Political Activities ◽  
The Core ◽  
The Common

Guanxi circle play a critical role in ancient China politics. Based on guanxi, two kinds of guanxi groups formed: formal guanxi circle and informal guanxi circle. The former refers to the group centered the emperor; the latter refers to the groups with the powerful and charismatic figures as the core, except for the emperor. In order to consolidate the political power, the emperors in different periods would try to prevent the informal guanxi circle in political structure. Besides, various scriptures also denounce the informal guanxi circle, deeming such circle as harmful. The judgement of informal guanxi circle appeals to research, as there is no previous researcher has address such problems. This study set out to examine whether the informal guanxi circle is harmful to the whole political structure. Results show that the informal guanxi circle, in the antecedent of satisfactory communication, can be extremely meaningful to the whole political structure. This study implies that the fact of informal guanxi circle is on the contrary of the common sense derived from the scriptures and the superficial ancient political activities, such as the emperor’s order to prevent the informal guanxi circle. The findings can contribute a better understanding of the ancient informal guanxi circle in ancient political structure in China.

scholarly journals The electrophysiological mapping of compartments within a mammalian cell.

1977 ◽  
Vol 72 (1) ◽  
pp. 86-103 ◽  
Author(s):  
D Giulian ◽  
E G Diacumakos
Keyword(s):  
Electron Microscope ◽  
Electrical Properties ◽  
Intact Cell ◽  
Living Cells ◽  
Microscope Examination ◽  
New Approach ◽  
Golgi Region ◽  
Grounding Electrode ◽  
Combination Of Methods ◽  
Peak Value

The electrical properties of structures within an intact cell were examined by impalement with micropipette electrodes. Mean potential differences (PDs) measured from interphase HeLa cells showed that internal membrane-bounded compartments such as the nucleus, Golgi region, and the mitochondria were more negative than the cytoplasm with respect to an external grounding electrode. The nuclear PDs, unlike Golgi and cytoplasmic PDs, shifted during interphase and reached a peak value shortly before mitosis. The positioning of micropipettes was confirmed by electron microscope examination of marker solutions that were microinjected into specific intracellular regions. The combination of methods described here offers a new approach for the study of physiological events within intact, living cells.

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