quiescent state
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2022 ◽  
Author(s):  
Daniel I Benjamin ◽  
Pieter I Both ◽  
Joel S Benjamin ◽  
Christopher W Nutter ◽  
Jenna H Tan ◽  
...  

Short-term fasting is beneficial for the regeneration of multiple tissue types. However, the effects of fasting on muscle regeneration are largely unknown. Here we report that fasting slows muscle repair both immediately after the conclusion of fasting as well as after multiple days of refeeding. We show that ketosis, either endogenously produced during fasting or a ketogenic diet, or exogenously administered, promotes a deep quiescent state in muscle stem cells(MuSCs). Although deep quiescent MuSCs are less poised to activate, slowing muscle regeneration, they have markedly improved survival when facing sources of cellular stress. Further, we show that ketone bodies, specifically b hydroxybutyrate, directly promote MuSC deep quiescence via a non-metabolic mechanism. We show that b-hydroxybutyrate functions as an HDAC inhibitor within MuSCs leading to acetylation and activation of an HDAC1 target protein p53. Finally, we demonstrate that p53 activation contributes to the deep quiescence and enhanced resilience observed during fasting.


2022 ◽  
Vol 225 (1) ◽  
Author(s):  
Madeleine S. Junkins ◽  
Sviatoslav N. Bagriantsev ◽  
Elena O. Gracheva

ABSTRACT Hibernators thrive under harsh environmental conditions instead of initiating canonical behavioral and physiological responses to promote survival. Although the physiological changes that occur during hibernation have been comprehensively researched, the role of the nervous system in this process remains relatively underexplored. In this Review, we adopt the perspective that the nervous system plays an active, essential role in facilitating and supporting hibernation. Accumulating evidence strongly suggests that the hypothalamus enters a quiescent state in which powerful drives to thermoregulate, eat and drink are suppressed. Similarly, cardiovascular and pulmonary reflexes originating in the brainstem are altered to permit the profoundly slow heart and breathing rates observed during torpor. The mechanisms underlying these changes to the hypothalamus and brainstem are not currently known, but several neuromodulatory systems have been implicated in the induction and maintenance of hibernation. The intersection of these findings with modern neuroscience approaches, such as optogenetics and in vivo calcium imaging, has opened several exciting avenues for hibernation research.


2022 ◽  
Vol 17 (1) ◽  
pp. 82-95
Author(s):  
Marina Arjona ◽  
Armon Goshayeshi ◽  
Cristina Rodriguez-Mateo ◽  
Jamie O. Brett ◽  
Pieter Both ◽  
...  

2021 ◽  
Author(s):  
Chung-Yen Huang ◽  
Yu-Chen Pai ◽  
Linda Chia-Hui Yu

Abstract Background: Altered glucose metabolism is associated with chemoresistance in colorectal cancer (CRC). The aim of this study was to illustrate the molecular mechanisms of glucose-mediated chemoresistance against irinotecan, a topoisomerase I inhibitor, focusing on the distinct roles of metabolites such as pyruvate and ATP in modulating cell death and proliferation. Methods: Four human CRC cell lines, tumorspheres, and mouse xenograft models were treated with various doses of irinotecan in the presence of high concentrations of glucose, pyruvate or ATP-encapsulated liposomes. Cell apoptosis was measured by DNA fragmentation and caspase activities, and necroptosis was evaluated by immunoprecipitation of receptor-interacting protein kinase (RIP) 1/3 complex. Cell cycles were assessed by flow cytometric analysis.Results: Human CRC cell lines treated with irinotecan in the presence of high glucose displayed increased cell viability and larger xenograft tumor sizes in mouse models compared to those treated in the presence of normal glucose. Irinotecan induced apoptosis and necroptosis, both of which were mitigated by high glucose. Liposomal ATP prevented irinotecan-induced apoptosis, while it had no effect on necroptosis. In contrast, pyruvate attenuated the RIP1/3-dependent necroptosis via free radical scavenging, without modulating apoptotic levels. Regarding the cell cycle, liposomal ATP aggravated irinotecan-induced G0/G1 shift whereas pyruvate diminished the G0/G1 shift, showing opposite effects on proliferation. Last, tumorsphere structural damage, an index of solid tumor responsiveness to chemotherapy, was determined. Liposomal ATP increased tumorsphere sizes while pyruvate prevented the deformation of spheroid mass. Conclusions: Glucose metabolites confer tumor chemoresistance via multiple modes of action. Glycolytic pyruvate attenuated irinotecan-induced necroptosis and potentiated drug insensitivity by shifting cells from a proliferative to quiescent state. On the other hand, ATP decreased irinotecan-induced apoptosis and promoted active cell proliferation, which might contribute to tumor recurrence.


2021 ◽  
Author(s):  
Yang Yang ◽  
Liyang Shi ◽  
Xiuling Fu ◽  
Gang Ma ◽  
Yang Zhongzhou ◽  
...  

Around 60% of in vitro fertilized (IVF) human embryos irreversibly arrest before compaction between the 3-8-cell stage, posing a significant clinical problem. The mechanisms behind this arrest are unclear. Here, we show that the arrested embryos enter a quiescent-like state, marked by cell cycle arrest, the downregulation of ribosomes and histones and downregulation of MYC and p53 activity. Mechanistically, the arrested embryos can be divided into three types. Type I embryos fail to complete the maternal-zygotic transition, and type II/III embryos have erroneously low levels of glycolysis and variable levels of oxidative phosphorylation. Treatment with resveratrol or nicotinamide riboside (NR) can partially rescue the arrested phenotype. The mechanism of reactivation involves the upregulation of SIRT1, and activation of glycolysis and fatty acid oxidation which forces the embryos out of a quiescent state. Overall, our data reveal how human embryo arrest can be overcome by modulating metabolic pathways.


Materials ◽  
2021 ◽  
Vol 14 (24) ◽  
pp. 7786
Author(s):  
Ivan Fortelný ◽  
Josef Jůza

This paper summarizes the results of studies describing the effect of block and graft copolymers on the phase structure formation and evolution in immiscible polymer blends. The main phenomenological rules for prediction of the copolymer compatibilization efficiency are briefly described and compared with selected experimental data. The results of the theories of equilibrium distribution of a copolymer between the blend interface and the bulk phases and its effect on the blend interfacial tension are summarized. The theories of the compatibilizer effect on the droplet breakup in flow are analyzed. The mechanisms of the copolymer effect on the coalescence of droplets in flow are compared and their effect on the droplet size is shown. The problems of reliable description of the effect of a copolymer on the coalescence in quiescent state are presented. Obstacles to derivation of a realistic theory of the copolymer effect on the competition between the droplet breakup and coalescence are discussed. Selected experimental data are compared with the theoretical results.


Author(s):  
Tanja Schuster ◽  
Hartmut Geiger

Septins were first described in yeast. Due to extensive research in non-yeast cells, Septins are now recognized across all species as important players in the regulation of the cytoskeleton, in the establishment of polarity, for migration, vesicular trafficking and scaffolding. Stem cells are primarily quiescent cells, and this actively maintained quiescent state is critical for proper stem cell function. Equally important though, stem cells undergo symmetric or asymmetric division, which is likely linked to the level of symmetry found in the mother stem cell. Due to the ability to organize barriers and be able to break symmetry in cells, Septins are thought to have a significant impact on organizing quiescence as well as the mode (symmetric vs asymmetric) of stem cell division to affect self-renewal versus differentiation. Mechanisms of regulating mammalian quiescence and symmetry breaking by Septins are though still somewhat elusive. Within this overview article, we summarize current knowledge on the role of Septins in stem cells ranging from yeast to mice especially with respect to quiescence and asymmetric division, with a special focus on hematopoietic stem cells.


Author(s):  
Magdaleena Naemi Mbadhi ◽  
Jun-ming Tang ◽  
Jing-xuan Zhang

Satellite stem cell availability and high regenerative capacity have made them an ideal therapeutic approach for muscular dystrophies and neuromuscular diseases. Adult satellite stem cells remain in a quiescent state and become activated upon muscular injury. A series of molecular mechanisms succeed under the control of epigenetic regulation and various myogenic regulatory transcription factors myogenic regulatory factors, leading to their differentiation into skeletal muscles. The regulation of MRFs via various epigenetic factors, including DNA methylation, histone modification, and non-coding RNA, determine the fate of myogenesis. Furthermore, the development of histone deacetylation inhibitors (HDACi) has shown promising benefits in their use in clinical trials of muscular diseases. However, the complete application of using satellite stem cells in the clinic is still not achieved. While therapeutic advancements in the use of HDACi in clinical trials have emerged, histone methylation modulations and the long non-coding RNA (lncRNA) are still under study. A comprehensive understanding of these other significant epigenetic modulations is still incomplete. This review aims to discuss some of the current studies on these two significant epigenetic modulations, histone methylation and lncRNA, as potential epigenetic targets in skeletal muscle regeneration. Understanding the mechanisms that initiate myoblast differentiation from its proliferative state to generate new muscle fibres will provide valuable information to advance the field of regenerative medicine and stem cell transplant.


2021 ◽  
Vol 922 (2) ◽  
pp. 222
Author(s):  
Shifeng Huang ◽  
Hongxing Yin ◽  
Shaoming Hu ◽  
Xu Chen ◽  
Yunguo Jiang ◽  
...  

Abstract Blazar PG 1553+113 is thought to be a host of supermassive black hole binary system. A 2.2 yr quasi-periodicity in the γ-ray light curve was detected, possibly a result of jet precession. Motivated by the previous studies based on the γ-ray data, we analyzed the X-ray light curve and spectra observed during 2012–2020. The 2.2 yr quasi-periodicity might be consistent with the main-flare recurrence in the X-ray light curve. When a weak rebrightening in the γ-ray was observed, a corresponding relatively strong brightening in the X-ray light curve can be identified. The harder-when-brighter tendency in both X-ray main and weak flares was shown, as well as a weak softer-when-brighter behavior for the quiescent state. We explore the possibility that the variability in the X-ray band can be interpreted with two-jet precession scenario. Using the relation between jets and accretion disks, we derive the primary black hole mass ≃3.47 × 108 M ☉ and mass of the secondary one ≃1.40 × 108 M ☉, and their mass ratio ∼0.41.


2021 ◽  
Vol 922 (2) ◽  
pp. 111
Author(s):  
Yi Xing ◽  
Zhongxiang Wang

Abstract The microquasar V404 Cygni (also known as GS 2023+338) was previously reported to have weak GeV γ-ray emission in subday time periods during its 2015 outburst. In order to provide more detailed information at the high energy range for this black hole binary system, we conduct analysis on the data obtained with the Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope (Fermi). Both the LAT database and source catalog used are the latest versions. In addition to the previously reported detection at the peak of the 2015 outburst, we find a possible detection (∼4σ) of the source during the 3 day time period of 2015 August 17–19 (at the end of the 2015 outburst) and one convincing detection (≃7σ) in 2016 August 23–25. The latter high-significance detection shows that the γ-ray emission of the source is soft with photon index Γ ∼ 2.9. As γ-ray emission from microquasars is considered to be associated with their jet activity, we discuss the results by comparing with those well-studied cases, namely, Cyg X-3 and Cyg X-1. The detection helps identify V404 Cygni as a microquasar with detectable γ-ray emission in its quiescent state, and adds interesting features to the microquasar group, or in a more general context to X-ray binaries with jets.


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