scholarly journals Control of tissue homeostasis, tumorigenesis, and degeneration by coupled bidirectional bistable switches

2021 ◽  
Vol 17 (11) ◽  
pp. e1009606
Author(s):  
Diego Barra Avila ◽  
Juan R. Melendez-Alvarez ◽  
Xiao-Jun Tian
Keyword(s):  
Regulatory Network ◽  
Physiological State ◽  
Critical Role ◽  
Feedback Loops ◽  
Tissue Homeostasis ◽  
State Transitions ◽  
Stochastic Fluctuations ◽  
The One ◽  
Theoretical Analyses ◽  
Complex Regulatory Network

The Hippo-YAP/TAZ signaling pathway plays a critical role in tissue homeostasis, tumorigenesis, and degeneration disorders. The regulation of YAP/TAZ levels is controlled by a complex regulatory network, where several feedback loops have been identified. However, it remains elusive how these feedback loops contain the YAP/TAZ levels and maintain the system in a healthy physiological state or trap the system in pathological conditions. Here, a mathematical model was developed to represent the YAP/TAZ regulatory network. Through theoretical analyses, three distinct states that designate the one physiological and two pathological outcomes were found. The transition from the physiological state to the two pathological states is mechanistically controlled by coupled bidirectional bistable switches, which are robust to parametric variation and stochastic fluctuations at the molecular level. This work provides a mechanistic understanding of the regulation and dysregulation of YAP/TAZ levels in tissue state transitions.

scholarly journals Accurate timekeeping is controlled by a cycling activator in Arabidopsis

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Polly Yingshan Hsu ◽  
Upendra K Devisetty ◽  
Stacey L Harmer
Keyword(s):  
Regulatory Network ◽  
Clock Gene ◽  
Regulatory Mechanism ◽  
Clock Genes ◽  
Feedback Loops ◽  
Transcriptional Repressors ◽  
Gene Transcripts ◽  
And Control ◽  
Complex Regulatory Network ◽  
Transcriptional Feedback

Transcriptional feedback loops are key to circadian clock function in many organisms. Current models of the Arabidopsis circadian network consist of several coupled feedback loops composed almost exclusively of transcriptional repressors. Indeed, a central regulatory mechanism is the repression of evening-phased clock genes via the binding of morning-phased Myb-like repressors to evening element (EE) promoter motifs. We now demonstrate that a related Myb-like protein, REVEILLE8 (RVE8), is a direct transcriptional activator of EE-containing clock and output genes. Loss of RVE8 and its close homologs causes a delay and reduction in levels of evening-phased clock gene transcripts and significant lengthening of clock pace. Our data suggest a substantially revised model of the circadian oscillator, with a clock-regulated activator essential both for clock progression and control of clock outputs. Further, our work suggests that the plant clock consists of a highly interconnected, complex regulatory network rather than of coupled morning and evening feedback loops.

Heterogeneity and Proliferative and Differential Regulators of NG2-glia in Physiological and Pathological States

2020 ◽  
Vol 27 (37) ◽  
pp. 6384-6406 ◽  
Author(s):  
Zuo Zhang ◽  
Hongli Zhou ◽  
Jiyin Zhou
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Physiological State ◽  
Critical Role ◽  
Adult Brain ◽  
Pathological State ◽  
Peripheral Neurons ◽  
Neuronal Synapses ◽  
The Central Nervous System ◽  
Rapid Modulation

NG2-glia, also called Oligodendrocyte Precursor Cells (OPCs), account for approximately 5%-10% of the cells in the developing and adult brain and constitute the fifth major cell population in the central nervous system. NG2-glia express receptors and ion channels involved in rapid modulation of neuronal activities and signaling with neuronal synapses, which have functional significance in both physiological and pathological states. NG2-glia participate in quick signaling with peripheral neurons via direct synaptic touches in the developing and mature central nervous system. These distinctive glia perform the unique function of proliferating and differentiating into oligodendrocytes in the early developing brain, which is critical for axon myelin formation. In response to injury, NG2-glia can proliferate, migrate to the lesions, and differentiate into oligodendrocytes to form new myelin sheaths, which wrap around damaged axons and result in functional recovery. The capacity of NG2-glia to regulate their behavior and dynamics in response to neuronal activity and disease indicate their critical role in myelin preservation and remodeling in the physiological state and in repair in the pathological state. In this review, we provide a detailed summary of the characteristics of NG2-glia, including their heterogeneity, the regulators of their proliferation, and the modulators of their differentiation into oligodendrocytes.

scholarly journals Antimicrobial multidrug resistance in the era of COVID-19: a forgotten plight?

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Eric Pelfrene ◽  
Radu Botgros ◽  
Marco Cavaleri
Keyword(s):  
Public Health ◽  
Multidrug Resistance ◽  
Regulatory Network ◽  
One Health ◽  
Animal Health ◽  
Antibiotic Use ◽  
Economic Conditions ◽  
Main Body ◽  
The One ◽  
The Relationship

Abstract Background Antimicrobial resistance (AMR) is a growing global problem to which the ongoing COVID-19 pandemic may further contribute. With resources deployed away from antimicrobial stewardship, evidence of substantial pre-emptive antibiotic use in COVID-19 patients and indirectly, with deteriorating economic conditions fuelling poverty potentially impacting on levels of resistance, AMR threat remains significant. Main body In this paper, main AMR countermeasures are revisited and priorities to tackle the issue are re-iterated. The need for collaboration is stressed, acknowledging the relationship between human health, animal health and environment (“One Health” approach). Among the stated priorities, the initiative by the European Medicines Regulatory Network to further strengthen the measures in combatting AMR is highlighted. Likewise, it is asserted that other emerging health threats require global collaboration with the One Health approach offering a valuable blueprint for action. Conclusion The authors stress the importance of an integrated preparedness strategy to tackle this public health peril.

Eternal Guests, Mimics, and Dönme: The Place of German and Turkish Jews in Modern Turkey

2007 ◽  
Vol 37 ◽  
pp. 5-30 ◽  
Author(s):  
Kader Konuk
Keyword(s):  
Critical Role ◽  
The Other ◽  
Turkish Republic ◽  
German Jews ◽  
Other Hand ◽  
Turkish Culture ◽  
The Status ◽  
Modern Turkey ◽  
The One ◽  
European Civilization

AbstractThe place of Jews was highly ambiguous in the newly founded Turkish Republic: In 1928 an assimilationist campaign was launched against Turkish Jews, while only a few years later, in 1933, German scholars—many of them Jewish—were taken in so as to help Europeanize the nation. Turkish authorities regarded the emigrants as representatives of European civilization and appointed scholars like Erich Auerbach to prestigious academic positions that were vital for redefining the humanities in Turkey. This article explores the country's twofold assimilationist policies. On the one hand, Turkey required of its citizens—regardless of ethnic or religious origins—that they conform to a unified Turkish culture; on the other hand, an equally assimilationist modernization project was designed to achieve cultural recognition from the heart of Europe. By linking historical and contemporary discourses, this article shows how tropes of Jewishness have played—and continue to play—a critical role in the conception of Turkish nationhood. The status of Erich Auerbach, Chair of the Faculty for Western Languages and Literatures at İstanbul University from 1936 to 1947, is central to this investigation into the place of Turkish and German Jews in modern Turkey.

scholarly journals ARMC Subfamily: Structures, Functions, Evolutions, Interactions, and Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Yutao Huang ◽  
Zijian Jiang ◽  
Xiangyu Gao ◽  
Peng Luo ◽  
Xiaofan Jiang
Keyword(s):  
Signal Transduction ◽  
Amino Acids ◽  
Cell Adhesion ◽  
Tandem Repeats ◽  
Critical Role ◽  
The Other ◽  
Biological Functions ◽  
Armadillo Repeat ◽  
The One ◽  
Similar Domain

Armadillo repeat-containing proteins (ARMCs) are widely distributed in eukaryotes and have important influences on cell adhesion, signal transduction, mitochondrial function regulation, tumorigenesis, and other processes. These proteins share a similar domain consisting of tandem repeats approximately 42 amino acids in length, and this domain constitutes a substantial platform for the binding between ARMCs and other proteins. An ARMC subfamily, including ARMC1∼10, ARMC12, and ARMCX1∼6, has received increasing attention. These proteins may have many terminal regions and play a critical role in various diseases. On the one hand, based on their similar central domain of tandem repeats, this ARMC subfamily may function similarly to other ARMCs. On the other hand, the unique domains on their terminals may cause these proteins to have different functions. Here, we focus on the ARMC subfamily (ARMC1∼10, ARMC12, and ARMCX1∼6), which is relatively conserved in vertebrates and highly conserved in mammals, particularly primates. We review the structures, biological functions, evolutions, interactions, and related diseases of the ARMC subfamily, which involve more than 30 diseases and 40 bypasses, including interactions and relationships between more than 100 proteins and signaling molecules. We look forward to obtaining a clearer understanding of the ARMC subfamily to facilitate further in-depth research and treatment of related diseases.

Nutritional biomarkers and machine learning for personalized nutrition applications and health optimization

2021 ◽  
pp. 1-9
Author(s):  
Dimitrios P. Panagoulias ◽  
Dionisios N. Sotiropoulos ◽  
George A. Tsihrintzis
Keyword(s):  
Machine Learning ◽  
Physiological State ◽  
Prediction Method ◽  
Disease Diagnosis ◽  
Classification Model ◽  
Cell Physiology ◽  
Cellular Processes ◽  
General Evaluation ◽  
Model Training ◽  
The One

The doctrine of the “one size fits all” approach in the field of disease diagnosis and patient management is being replaced by a more per patient approach known as “personalized medicine”. In this spirit, biomarkers are key variables in the research and development of new methods for prognostic and classification model training based on advances in the field of artificial intelligence [1, 2, 3]. Metabolomics refers to the systematic study of the unique chemical fingerprints that cellular processes leave behind. The metabolic profile of a person can provide a snapshot of cell physiology and, by extension, metabolomics provide a direct “functional reading of the physiological state” of an organism. Via employing machine learning methodologies, a general evaluation chart of nutritional biomarkers is formulated and an optimised prediction method for body to mass index is investigated with the aim to discover dietary patterns.

Asia’s Mediterranean

2017 ◽  
Author(s):  
Jude Woodward
Keyword(s):  
South China Sea ◽  
South China ◽  
Critical Role ◽  
The South China Sea ◽  
The South ◽  
American Power ◽  
China Sea ◽  
The Us ◽  
Dramatic Shift ◽  
The One

This chapter (and the next) look at the US’s recent intervention in the South China Sea and China’s responses. It considers the varying domestic and strategic concerns of these primarily island countries. It analyses the drivers of their responses to the sovereignty disputes in the Sea and to the key US initiative of the TPP. This chapter and the next are linked to the one that follows on Vietnam, which also plays a critical role in the shifting relation of forces in the South China Sea disputes. This is the region where the US has invested most hopes in a dramatic shift in regional alignments against China. These chapters assess the US’s progress, and conclude that – despite its lack of a local ally with anything like the weight of Japan or South Korea and the immense geographic extension of American power involved in maintaining its presence in the region – in some respects the US ’rebalance’ strategies have made more progress here to China’s south than to its east.

The Duel and the Daïs: Iliadic Warfare as Spectacle

2019 ◽  
pp. 65-108
Author(s):  
Tobias Myers
Keyword(s):  
Critical Role ◽  
The Other ◽  
Mise En Abyme ◽  
Other Hand ◽  
The One ◽  
The Relationship

Chapter 2 explores how the Olympians and the Iliad’s audience are positioned as viewers for the warfare in Books 1–4, and their roles defined. The first section focuses on the gods. Homer initially defines the gods’ role as viewers by drawing on two specific paradigms of live event: entertainment at a daïs (banquet), and the formal duel. Each of these paradigms carries its own suggestions as to the nature of the event, its stakes, and the relationship between viewer and action. As entertainment accompanying a daïs, the warfare may generate pleasure (terpein) for viewers whose critical role is to praise or blame the dramatic figure pulling the strings. As a spectacle modelled on the formal duel, the warfare is observed by implicated, partisan viewers, who are themselves a part of the conflict, and can become actors by entering the central space. Rich tension is generated by the combination of these paradigms. The chapter’s second section reads the opening of Book 4, in which the gods watch a duel from their daïs, as a mise en abyme of the spectacle experience offered by the Iliad to its listeners. On the one hand, the combination of duel and daïs shapes audience understanding of the kind of spectacle that they, too, are witnessing, and their own relationship to the action. On the other hand, the gods’ particular responses—both to the events on the ground and to their staging and direction—dramatize possible responses on the part of Homer’s audience.

scholarly journals Neural Differentiation Dynamics Controlled by Multiple Feedback Loops in a Comprehensive Molecular Interaction Network

Processes ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 166
Author(s):  
Tsuyoshi Iwasaki ◽  
Ryo Takiguchi ◽  
Takumi Hiraiwa ◽  
Takahiro G. Yamada ◽  
Kazuto Yamazaki ◽  
...  
Keyword(s):  
Regulatory Network ◽  
Neural Differentiation ◽  
Large Scale ◽  
Model Simulation ◽  
Interaction Network ◽  
Feedback Loops ◽  
Characteristic Change ◽  
Large Network ◽  
Large Scale Network ◽  
Scale Network

Mathematical model simulation is a useful method for understanding the complex behavior of a living system. The construction of mathematical models using comprehensive information is one of the techniques of model construction. Such a comprehensive knowledge-based network tends to become a large-scale network. As a result, the variation of analyses is limited to a particular kind of analysis because of the size and complexity of the model. To analyze a large-scale regulatory network of neural differentiation, we propose a contractive method that preserves the dynamic behavior of a large network. The method consists of the following two steps: comprehensive network building and network reduction. The reduction phase can extract network loop structures from a large-scale regulatory network, and the subnetworks were combined to preserve the dynamics of the original large-scale network. We confirmed that the extracted loop combination reproduced the known dynamics of HES1 and ASCL1 before and after differentiation, including oscillation and equilibrium of their concentrations. The model also reproduced the effects of the overexpression and knockdown of the Id2 gene. Our model suggests that the characteristic change in HES1 and ASCL1 expression in the large-scale regulatory network is controlled by a combination of four feedback loops, including a large loop, which has not been focused on. The model extracted by our method has the potential to reveal the critical mechanisms of neural differentiation. The method is applicable to other biological events.

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