Estrogens, Xenoestrogens, and the Development of Neoplasms
Rajesh K. Naz in Endocrine Disruptors, 2004
Self-replication is the sine qua non of life. It is generally accepted that proliferation is a built-in property of the cells of unicellular organisms and metaphyta. Unicellular organisms and metaphyta cells dissociated from tissues and placed in culture proliferate maximally as long as they are exposed to nutrients. The state of proliferative quiescence appeared with the advent of multicellularity. There are only two possible choices: The default state of cells in metazoa is either quiescence or proliferation. Most researchers studying metazoa assume that the quiescent state observed in situ is their default state. This means that cells will not proliferate unless stimulated. However, from an evolutionary perspective, this argument is not compelling since multicellular organisms evolved from unicellular ones. Every organism starts as a single cell, the egg. It is highly unlikely for that single cell to forgo the property of self-replication. An almost complete homology between the machinery to replicate yeast cells and human cells suggests that the machinery for cell replication has remained constant throughout evolution.67
The neurobiology of sleep
Philip N. Murphy in The Routledge International Handbook of Psychobiology, 2018
A temporal organization is observed in all animal species – from single-cell organisms to mammals. The most common component of these time-domain changes is a regular transition from an active state to a resting state. The resting state is referred to as “sleep” when the following behavioral features are present: (i) behavioral quiescence, (ii) an increased arousal threshold, (iii) rapid reversibility (for the transition to wakefulness), and (iv) a species-specific location and posture. Sleep states have been clearly evidenced in mammals, birds and reptiles, and there is a growing body of evidence for sleep-like states in amphibians, fishes and even some invertebrates (Hartse, 2011; McNamara et al., 2008). However, the presence of several different states within sleep has only been conclusively documented for warm-blooded vertebrates (mammals and birds). As detailed below, each of these states is associated with a characteristic pattern of brain activity and is accompanied by specific autonomic and behavioral signs. The occurrence of sleep depends on both circadian organization and homeostatic regulation (Borbély, Daan, Wirz-Justice, & Deboer, 2016). Circadian rhythms define the duration and position of sleep during the 24-hour period, modulated by synchronizers, such as meal-time regularity and bed time in humans, whereas homeostatic regulation generates sleep pressure as a function of the time spent awake. In humans, sleep is constituted by three to six 90- to 120-minute cycles per night.
Appetite Control in C. elegans
Ruth B.S. Harris in Appetite and Food Intake, 2017
Previous studies found that a gain of function mutant of egl-4, which encodes a cGMP-dependent protein kinase, shows excessive quiescence under conditions where the wild-type worms do not show quiescence (Avery 1993a, Raizen et al. 2006). You et al. (2008) found that egl-4 loss of function mutants show no satiety quiescence, whereas the gain of function mutation shows excessive satiety quiescence. This finding suggested a role for cGMP signaling in satiety quiescence, confirmed by the fact that the membrane guanylate cyclase and C. elegans homolog of a natriuretic peptide (NP) receptor, DAF-11, and the cGMP-gated cation channel are necessary for satiety quiescence (You et al. 2008). In C. elegans, insulin, TGFβ, and cGMP pathways are used in sensing a favorable environment and in making the developmental decision to keep growing and reproducing instead of becoming a dauer, a nonreproductive form specialized for long-term survival (Riddle et al. 1981). In other words, these signals are used to ensure that worms will be in nutritionally favorable conditions. The findings of You et al. imply that these same signals of favorable conditions are used to exhibit satiety quiescence in adults.
Research progress on therapeutic targeting of quiescent cancer cells
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Jinhua Zhang, Jing Si, Lu Gan, Cuixia Di, Yi Xie, Chao Sun, Hongyan Li, Menghuan Guo, Hong Zhang
Quiescence is defined as a reversible cellular state from which the cells are able to re-enter the proliferative cycle in response to certain promitogenic factors, including cell-extrinsic environmental signals (e.g. injury or tumor acidification) and cell-intrinsic regulatory mechanisms [1,2]. Scientific literature to date supports the existence of quiescent cancer cells in many tumor types, including breast, liver and pancreatic cancer, acute myeloid leukaemia, melanoma, and glioblastoma [3,4]. In earlier studies, cells were induced to quiescence via serum starvation (whereby cells at low density were grown in serum-free medium) or contact inhibition (cells were grown in 10% serum until complete confluence) [5–7]. Quiescent cells were confirmed based on the lack of expression of Ki67 (a cell proliferation marker), negative EDU incorporation [7] or low rate of BrdU incorporation [3], and low Erk 1/2: p38 MAPK ratio [6–8]. Moreover, mVenus-p27K−, a fusion protein composed of the fluorescent protein mVenus and a defective mutant of p27 combined with Fucci probe could effectively recognize and distinguish cells at G0 from those at G1 during the G0-G1 transition state [9,10].
Abemaciclib: safety and effectiveness of a unique cyclin-dependent kinase inhibitor
Published in Expert Opinion on Drug Safety, 2020
Vittorio Gebbia, Maria Rosaria Valerio, Alberto Firenze, Paolo Vigneri
Differently, from other CDK4/6i, abemaciclib induces extensive metabolic alterations in BC cells [9,21], which may explain the partial absence of cross-resistance with palbociclib [16,21]. These metabolic effects correlate to an irreversible cell-cycle arrest and induction of senescence and apoptosis, which have occurred very early at doses much lower than those required for other CDK4/6i [21–23]. Abemaciclib may alter mitochondrial function, causing a time-dependent reduction in the concentration of the TCA metabolites α-ketoglutarate, fumarate, and malate, together with a minor decrease in succinate concentration. The transition from quiescence to senescence is known as geroconversion [24]. Senescence is a form of permanent growth arrest characterized by morphological changes, senescence-associated beta-galactosidase activity, presence of senescence-associated heterochromatin foci, and production of growth factors, cytokines, proteases, and other proteins and matrix-degrading molecules, collectively known as the senescence-associated secretory phenotype.
Discriminating between sleep and exercise-induced fatigue using computer vision and behavioral genetics
Published in Journal of Neurogenetics, 2020
Kelsey N. Schuch, Lakshmi Narasimhan Govindarajan, Yuliang Guo, Saba N. Baskoylu, Sarah Kim, Benjamin Kimia, Thomas Serre, Anne C. Hart
C. elegans locomotory behavior after prolonged swimming has not been thoroughly studied. Previous studies were limited by reliance on manual annotation, which hinders research depth, or by reliance on constrictive microfluidic devices, which may induce mechanical stress (Ghosh & Emmons, 2008; Gonzales, Zhou, Fan, & Robinson, 2019). Using both of our new systems, we can provide a detailed analysis of how C. elegans locomotory behaviors change after prolonged swimming. When comparing wild type and egl-4 mutant animals, differences were found in multiple parameters, including wave initiation rate at early and late time points. Interestingly, there were also differences in which locomotion parameters changed over time between wild type and mutant animals. For example, curling activity and stretch were found to change over time in wild type animals, but not in egl-4 mutant animals. In future studies of C. elegans fatigue, parameters like wave initiation rate and brush stroke will likely provide information about how vigorously an animal swims and can be used to track decreased muscle output after prolonged swimming exercise. We note that quiescence levels can vary across experiments, even in wild type animals. This may be caused by differences in ambient conditions during rearing (e.g. humidity levels, vibration). Here, all experimental groups in a trial were reared in tandem to control for these differences.
Related Knowledge Centers
- Cell Growth
- Cellular Senescence
- DNA Damage
- G1 Phase
- Rna
- Cellular Differentiation
- Apoptosis
- Cell Cycle
- Neuron
- Restriction Point