scholarly journals The Importance of Stochastic Effects for Explaining Entrainment in the Zebrafish Circadian Clock

2015 ◽  
Vol 2015 ◽  
pp. 1-9
Author(s):  
Raphaela Heussen ◽  
David Whitmore
Keyword(s):  
Light Intensity ◽  
Circadian Clock ◽  
Light Exposure ◽  
Essential Feature ◽  
Strong Component ◽  
Stochastic Effects ◽  
Signal Decay ◽  
Physiological Processes ◽  
External Cues

The circadian clock plays a pivotal role in modulating physiological processes and has been implicated, either directly or indirectly, in a range of pathological states including cancer. Here we investigate how the circadian clock is entrained by external cues such as light. Working with zebrafish cell lines and combining light pulse experiments with simulation efforts focused on the role of synchronization effects, we find that even very modest doses of light exposure are sufficient to trigger some entrainment, whereby a higher light intensity or duration correlates with strength of the circadian signal. Moreover, we observe in the simulations that stochastic effects may be considered an essential feature of the circadian clock in order to explain the circadian signal decay in prolonged darkness, as well as light initiated resynchronization as a strong component of entrainment.

scholarly journals Circadian Clock Regulates Inflammation and the Development of Neurodegeneration

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiao-Lan Wang ◽  
Lianjian Li
Keyword(s):  
Circadian Clock ◽  
Immune Cells ◽  
Brain Function ◽  
Cellular Tissue ◽  
Physiological Processes ◽  
Circadian Control ◽  
Prevention And Treatment ◽  
Potential Strategy ◽  
Peripheral Immune Cells

The circadian clock regulates numerous key physiological processes and maintains cellular, tissue, and systemic homeostasis. Disruption of circadian clock machinery influences key activities involved in immune response and brain function. Moreover, Immune activation has been closely linked to neurodegeneration. Here, we review the molecular clock machinery and the diurnal variation of immune activity. We summarize the circadian control of immunity in both central and peripheral immune cells, as well as the circadian regulation of brain cells that are implicated in neurodegeneration. We explore the important role of systemic inflammation on neurodegeneration. The circadian clock modulates cellular metabolism, which could be a mechanism underlying circadian control. We also discuss the circadian interventions implicated in inflammation and neurodegeneration. Targeting circadian clocks could be a potential strategy for the prevention and treatment of inflammation and neurodegenerative diseases.

scholarly journals EARLY FLOWERING 3 controls temperature responsiveness of the circadian clock

2020 ◽  
Author(s):  
Zihao Zhu ◽  
Marcel Quint ◽  
Muhammad Usman Anwer
Keyword(s):  
Circadian Clock ◽  
Biological Rhythms ◽  
Early Flowering ◽  
Climate Change Scenarios ◽  
Temperature Changes ◽  
Physiological Processes ◽  
Average Global Temperature ◽  
Clock Component ◽  
Rhythmic Growth

SummaryPredictable changes in light and temperature during a diurnal cycle are major entrainment cues that enable the circadian clock to generate internal biological rhythms that are synchronized with the external environment. With the average global temperature predicted to keep increasing, the intricate light-temperature coordination that is necessary for clock functionality is expected to be seriously affected. Hence, understanding how temperature signals are perceived by the circadian clock has become an important issue, especially in light of climate change scenarios. In Arabidopsis, the clock component EARLY FLOWERING 3 (ELF3) not only serves as an essential light Zeitnehmer, but also functions as a thermosensor participating in thermomorphogenesis. However, the role of ELF3 in temperature entrainment of the circadian clock is not fully understood. Here, we report that ELF3 is essential for delivering temperature input to the clock. We demonstrate that in the absence of ELF3, the oscillator was unable to properly respond to temperature changes, resulting in an impaired gating of thermoresponses. Consequently, clock-controlled physiological processes such as rhythmic growth and cotyledon movement were disturbed. Together, our results reveal that ELF3 is an essential Zeitnehmer for temperature sensing of the oscillator, and thereby for coordinating the rhythmic control of thermoresponsive physiological outputs.

scholarly journals Modeling the Optimal Conditions for Improved Efficacy and Crosslink Depth of Photo-Initiated Polymerization

Polymers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 217 ◽  
Author(s):  
Jui-Teng Lin ◽  
Hsia-Wei Liu ◽  
Kuo-Ti Chen ◽  
Da-Chuan Cheng
Keyword(s):  
Light Intensity ◽  
Light Exposure ◽  
Spatial Average ◽  
Type I ◽  
Optimal Conditions ◽  
Action Process ◽  
Temporal Profiles ◽  
First Time ◽  
Concentration Diffusion

Optimal conditions for maximum efficacy of photoinitiated polymerization are theoretically presented. Analytic formulas are shown for the crosslink time, crosslink depth, and efficacy function. The roles of photoinitiator (PI) concentration, diffusion depth, and light intensity on the polymerization spatial and temporal profiles are presented for both uniform and non-uniform cases. For the type I mechanism, higher intensity may accelerate the polymer action process, but it suffers a lower steady-state efficacy. This may be overcome by a controlled re-supply of PI concentration during the light exposure. In challenging the conventional Beer–Lambert law (BLL), a generalized, time-dependent BLL (a Lin-law) is derived. This study, for the first time, presents analytic formulas for curing depth and crosslink time without the assumption of thin-film or spatial average. Various optimal conditions are developed for maximum efficacy based on a numerically-fit A-factor. Experimental data are analyzed for the role of PI concentration and light intensity on the gelation (crosslink) time and efficacy.

scholarly journals Light-mediated circuit switching in the Drosophila neuronal clock network

2019 ◽  
Author(s):  
M Schlichting ◽  
P Weidner ◽  
M Diaz ◽  
P Menegazzi ◽  
E Dalla-Benetta ◽  
...  
Keyword(s):  
Visual System ◽  
Circadian Clock ◽  
Molecular Mechanism ◽  
Essential Feature ◽  
Constant Darkness ◽  
Circuit Switching ◽  
Light Entrainment ◽  
Long Day ◽  
External Cues ◽  
A Cell

SummaryThe circadian clock is a timekeeper but also helps adapt physiology to the outside world. This is because an essential feature of clocks is their ability to adjust (entrain) to the environment, with light being the most important signal. Whereas Cryptochrome-mediated entrainment is well understood in Drosophila, integration of light information via the visual system lacks a neuronal or molecular mechanism. Here we show that a single photoreceptor sub-type is essential for long day adaptation. These cells activate key circadian neurons, namely the lLNvs, which release the neuropeptide PDF. Using a cell-specific CRISPR/Cas9 assay, we show that PDF directly interacts with neurons important for evening (E) activity timing. Interestingly, this pathway is specific for light entrainment and appears to be dispensable in constant darkness (DD). The results therefore indicate that external cues cause a rearrangement of neuronal hierarchy, which is a novel form of plasticity.

scholarly journals Melatonin in animal models

2003 ◽  
Vol 5 (4) ◽  
pp. 343-352
Keyword(s):  
Circadian Clock ◽  
Melatonin Receptors ◽  
Cellular Mechanisms ◽  
Exact Role ◽  
Physiological Processes ◽  
Timing System ◽  
Circadian Organization ◽  
Melatonin Production ◽  
Endogenous Melatonin

Melatonin is a hormone synthesized and secreted during the night by the pineal gland. Its production is mainly driven by the Orcadian clock, which, in mammals, is situated in the suprachiasmatic nucleus of the hypothalamus. The melatonin production and release displays characteristic daily (nocturnal) and seasonal patterns (changes in duration proportional to the length of the night) of secretion. These rhythms in circulating melatonin are strong synchronizers for the expression of numerous physiological processes. In mammals, the role of melatonin in the control of seasonality is well documented, and the sites and mechanisms of action involved are beginning to be identified. The exact role of the hormone in the diurnal (Orcadian) timing system remains to be determined. However, exogenous melatonin has been shown to affect the circadian clock. The molecular and cellular mechanisms involved in this well-characterized "chronobiotic" effect have also begun to be characterized. The circadian clock itself appears to be an important site for the entrapment effect of melatonin and the presence of melatonin receptors appears to be a prerequisite. A better understanding of such "chronobiotic" effects of melatonin will allow clarification of the role of endogenous melatonin in circadian organization.

scholarly journals Overview on the Different Patterns of Tumor Vascularization

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 639
Author(s):  
Domenico Ribatti ◽  
Francesco Pezzella
Keyword(s):  
Vasculogenic Mimicry ◽  
Endothelial Cell Proliferation ◽  
Published Data ◽  
Alternative Mechanism ◽  
Tumor Vascularization ◽  
Angiogenic Therapy ◽  
Physiological Processes ◽  
Inhibition Of Angiogenesis ◽  
Therapeutic Development

Angiogenesis is a crucial event in the physiological processes of embryogenesis and wound healing. During malignant transformation, dysregulation of angiogenesis leads to the formation of a vascular network of tumor-associated capillaries promoting survival and proliferation of the tumor cells. Starting with the hypothesis formulated by Judah Folkman that tumor growth is angiogenesis-dependent, this area of research has a solid scientific foundation and inhibition of angiogenesis is a major area of therapeutic development for the treatment of cancer. Over this period numerous authors published data of vascularization of tumors, which attributed the cause of neo-vascularization to various factors including inflammation, release of angiogenic cytokines, vasodilatation, and increased tumor metabolism. More recently, it has been demonstrated that tumor vasculature is not necessarily derived by endothelial cell proliferation and sprouting of new capillaries, but alternative vascularization mechanisms have been described, namely vascular co-option and vasculogenic mimicry. In this article, we have analyzed the mechanisms involved in tumor vascularization in association with classical angiogenesis, including post-natal vasculogenesis, intussusceptive microvascular growth, vascular co-option, and vasculogenic mimicry. We have also discussed the role of these alternative mechanism in resistance to anti-angiogenic therapy and potential therapeutic approaches to overcome resistance.

scholarly journals Phosphorylation of GAPVD1 Is Regulated by the PER Complex and Linked to GAPVD1 Degradation

2021 ◽  
Vol 22 (7) ◽  
pp. 3787
Author(s):  
Hussam Ibrahim ◽  
Philipp Reus ◽  
Anna Katharina Mundorf ◽  
Anna-Lena Grothoff ◽  
Valerie Rudenko ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Transcriptional Repression ◽  
Small Gtpase ◽  
Main Role ◽  
Interacting Proteins ◽  
Casein Kinase 1 ◽  
Bona Fide ◽  
Kinetics Of

Repressor protein period (PER) complexes play a central role in the molecular oscillator mechanism of the mammalian circadian clock. While the main role of nuclear PER complexes is transcriptional repression, much less is known about the functions of cytoplasmic PER complexes. We found with a biochemical screen for PER2-interacting proteins that the small GTPase regulator GTPase-activating protein and VPS9 domain-containing protein 1 (GAPVD1), which has been identified previously as a component of cytoplasmic PER complexes in mice, is also a bona fide component of human PER complexes. We show that in situ GAPVD1 is closely associated with casein kinase 1 delta (CSNK1D), a kinase that regulates PER2 levels through a phosphoswitch mechanism, and that CSNK1D regulates the phosphorylation of GAPVD1. Moreover, phosphorylation determines the kinetics of GAPVD1 degradation and is controlled by PER2 and a C-terminal autoinhibitory domain in CSNK1D, indicating that the regulation of GAPVD1 phosphorylation is a novel function of cytoplasmic PER complexes and might be part of the oscillator mechanism or an output function of the circadian clock.

scholarly journals Pannexins and Connexins: Their Relevance for Oocyte Developmental Competence

2021 ◽  
Vol 22 (11) ◽  
pp. 5918
Author(s):  
Paweł Kordowitzki ◽  
Gabriela Sokołowska ◽  
Marta Wasielak-Politowska ◽  
Agnieszka Skowronska ◽  
Mariusz T. Skowronski
Keyword(s):  
Assisted Reproductive Technologies ◽  
Mammalian Species ◽  
Atp Release ◽  
Reproductive Technologies ◽  
High Energy ◽  
Developmental Competence ◽  
Physiological Processes ◽  
Protein Group ◽  
Multicellular Organisms

The oocyte is the major determinant of embryo developmental competence in all mammalian species. Although fundamental advances have been generated in the field of reproductive medicine and assisted reproductive technologies in the past three decades, researchers and clinicians are still trying to elucidate molecular factors and pathways, which could be pivotal for the oocyte’s developmental competence. The cell-to-cell and cell-to-matrix communications are crucial not only for oocytes but also for multicellular organisms in general. This latter mentioned communication is among others possibly due to the Connexin and Pannexin families of large-pore forming channels. Pannexins belong to a protein group of ATP-release channels, therefore of high importance for the oocyte due to its requirements of high energy supply. An increasing body of studies on Pannexins provided evidence that these channels not only play a role during physiological processes of an oocyte but also during pathological circumstances which could lead to the development of diseases or infertility. Connexins are proteins that form membrane channels and gap-junctions, and more precisely, these proteins enable the exchange of some ions and molecules, and therefore they do play a fundamental role in the communication between the oocyte and accompanying cells. Herein, the role of Pannexins and Connexins for the processes of oogenesis, folliculogenesis, oocyte maturation and fertilization will be discussed and, at the end of this review, Pannexin and Connexin related pathologies and their impact on the developmental competence of oocytes will be provided.

scholarly journals Syndecans and Pancreatic Ductal Adenocarcinoma

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 349
Author(s):  
Nausika Betriu ◽  
Juan Bertran-Mas ◽  
Anna Andreeva ◽  
Carlos E. Semino
Keyword(s):  
Extracellular Matrix ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cell Types ◽  
Ductal Adenocarcinoma ◽  
Physiological Processes ◽  
Extracellular Matrix Components ◽  
Detection And Diagnosis ◽  
And Migration ◽  
Early Detection And Diagnosis

Pancreatic Ductal Adenocarcinoma (PDAC) is a fatal disease with poor prognosis because patients rarely express symptoms in initial stages, which prevents early detection and diagnosis. Syndecans, a subfamily of proteoglycans, are involved in many physiological processes including cell proliferation, adhesion, and migration. Syndecans are physiologically found in many cell types and their interactions with other macromolecules enhance many pathways. In particular, extracellular matrix components, growth factors, and integrins collect the majority of syndecans associations acting as biochemical, physical, and mechanical transducers. Syndecans are transmembrane glycoproteins, but occasionally their extracellular domain can be released from the cell surface by the action of matrix metalloproteinases, converting them into soluble molecules that are capable of binding distant molecules such as extracellular matrix (ECM) components, growth factor receptors, and integrins from other cells. In this review, we explore the role of syndecans in tumorigenesis as well as their potential as therapeutic targets. Finally, this work reviews the contribution of syndecan-1 and syndecan-2 in PDAC progression and illustrates its potential to be targeted in future treatments for this devastating disease.

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