Chaotic Dynamics and Stability of Liposomal Nanosystems

2021 ◽  
Vol 17 ◽  
Author(s):  
Nikolaos Naziris ◽  
Maria Chountoulesi ◽  
Stavros Stavrinides ◽  
Michael Hanias ◽  
Costas Demetzos
Keyword(s):  
Chaotic Dynamics ◽  
Chaotic Behavior ◽  
Severe Disease ◽  
Physical Stability ◽  
Vaccine Delivery ◽  
Cell Physiology ◽  
Cellular Functions ◽  
Research Topics ◽  
Loss Of Information ◽  
Disease States

Background: Natural and living systems are dynamical systems that demonstrate complex behavior, which appears to be deterministic chaotic, characterized and governed by entropy increase and loss of information throughout their entire lifespan. Lipidic nanoparticles, such as liposomes, as artificial biomembranes, have long been considered appropriate models for studying various membrane phenomena that cell systems exhibit. By utilizing these models, we can better comprehend cellular functions, stability, as well as factors that might alter the cell physiology, leading to severe disease states. In addition, liposomes are well-established drug and vaccine delivery nanosystems, which are present in the market, playing a significant role; therefore, due to their importance, issues concerning their effectiveness and stability are research topics that are constantly investigated and updated. Methods: In this study, the emergent deterministic chaotic behavior of liposomes is described, while evaluation in accordance to their colloidal physical stability, by utilizing established nonlinear dynamics tools, is presented. Two liposomes of different composition and physical stability were developed and a chaotic evaluation on the time series of their size and polydispersity was conducted. Results: The utilized models revealed instability, loss of information and order loss for both liposomes in due time, with important differentiation. An initial interpretation of the results is apposed, whereas the foundations for further investigating possible exploitation of the demonstrated nonlinearity and adaptability of artificial biomembranes is laid, with projection on biosystems. Conclusion: The present approach is expected to impact the application of lipidic nanoparticles and liposomes in various crucial fields, such as drug and vaccine delivery, providing useful information for academia and the industry.

scholarly journals Mechanism and disease association of E2-conjugating enzymes: lessons from UBE2T and UBE2L3

2016 ◽  
Vol 473 (20) ◽  
pp. 3401-3419 ◽  
Author(s):  
Arno F. Alpi ◽  
Viduth Chaugule ◽  
Helen Walden
Keyword(s):  
Ubiquitin Ligase ◽  
Severe Disease ◽  
Chromosome Instability ◽  
E3 Ubiquitin Ligase ◽  
Regulatory System ◽  
Disease Association ◽  
Cellular Functions ◽  
Disease States ◽  
Ubiquitin Binding

Ubiquitin signalling is a fundamental eukaryotic regulatory system, controlling diverse cellular functions. A cascade of E1, E2, and E3 enzymes is required for assembly of distinct signals, whereas an array of deubiquitinases and ubiquitin-binding modules edit, remove, and translate the signals. In the centre of this cascade sits the E2-conjugating enzyme, relaying activated ubiquitin from the E1 activating enzyme to the substrate, usually via an E3 ubiquitin ligase. Many disease states are associated with dysfunction of ubiquitin signalling, with the E3s being a particular focus. However, recent evidence demonstrates that mutations or impairment of the E2s can lead to severe disease states, including chromosome instability syndromes, cancer predisposition, and immunological disorders. Given their relevance to diseases, E2s may represent an important class of therapeutic targets. In the present study, we review the current understanding of the mechanism of this important family of enzymes, and the role of selected E2s in disease.

scholarly journals A computational framework for finding parameter sets associated with chaotic dynamics

2021 ◽  
pp. 1-11
Author(s):  
S. Koshy-Chenthittayil ◽  
E. Dimitrova ◽  
E.W. Jenkins ◽  
B.C. Dean
Keyword(s):  
Experimental Data ◽  
Dynamical Systems ◽  
Lyapunov Exponents ◽  
Parameter Space ◽  
Chaotic Dynamics ◽  
Chaotic Behavior ◽  
Computational Framework ◽  
Independent Variables ◽  
Systems Model ◽  
Small Support

Many biological ecosystems exhibit chaotic behavior, demonstrated either analytically using parameter choices in an associated dynamical systems model or empirically through analysis of experimental data. In this paper, we use existing software tools (COPASI, R) to explore dynamical systems and uncover regions with positive Lyapunov exponents where thus chaos exists. We evaluate the ability of the software’s optimization algorithms to find these positive values with several dynamical systems used to model biological populations. The algorithms have been able to identify parameter sets which lead to positive Lyapunov exponents, even when those exponents lie in regions with small support. For one of the examined systems, we observed that positive Lyapunov exponents were not uncovered when executing a search over the parameter space with small spacings between values of the independent variables.

Chaos in the Periodically Parametrically Excited Lorenz System

2021 ◽  
Vol 31 (08) ◽  
pp. 2130024
Author(s):  
Weisheng Huang ◽  
Xiao-Song Yang
Keyword(s):  
Chaotic Dynamics ◽  
Lorenz System ◽  
Stable Equilibrium ◽  
Chaotic Behavior ◽  
Equilibrium Points ◽  
Time Varying ◽  
Asymptotically Stable ◽  
Parametrically Excited ◽  
The Lorenz System

We demonstrate in this paper a new chaotic behavior in the Lorenz system with periodically excited parameters. We focus on the parameters with which the Lorenz system has only two asymptotically stable equilibrium points, a saddle and no chaotic dynamics. A new mechanism of generating chaos in the periodically excited Lorenz system is demonstrated by showing that some trajectories can visit different attractor basins due to the periodic variations of the attractor basins of the time-varying stable equilibrium points when a parameter of the Lorenz system is varying periodically.

scholarly journals Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Sanjana R. Sen ◽  
Emily C. Sanders ◽  
Kristin N. Gabriel ◽  
Brian M. Miller ◽  
Hariny M. Isoda ◽  
...  
Keyword(s):  
Risk Factor ◽  
Factor Score ◽  
Disease Risk ◽  
Severe Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Disease Risk Factor ◽  
Disease States ◽  
Wide Range ◽  
Risk Factor Score ◽  
Prognostic Prediction

ABSTRACT Effective methods for predicting COVID-19 disease trajectories are urgently needed. Here, enzyme-linked immunosorbent assay (ELISA) and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients (n = 86) experiencing a wide range of disease states. The experiments identified antibodies to a 21-residue epitope from nucleocapsid (termed Ep9) associated with severe disease, including admission to the intensive care unit (ICU), requirement for ventilators, or death. Importantly, anti-Ep9 antibodies can be detected within 6 days post-symptom onset and sometimes within 1 day. Furthermore, anti-Ep9 antibodies correlate with various comorbidities and hallmarks of immune hyperactivity. We introduce a simple-to-calculate, disease risk factor score to quantitate each patient’s comorbidities and age. For patients with anti-Ep9 antibodies, scores above 3.0 predict more severe disease outcomes with a 13.42 likelihood ratio (96.7% specificity). The results lay the groundwork for a new type of COVID-19 prognostic to allow early identification and triage of high-risk patients. Such information could guide more effective therapeutic intervention. IMPORTANCE The COVID-19 pandemic has resulted in over two million deaths worldwide. Despite efforts to fight the virus, the disease continues to overwhelm hospitals with severely ill patients. Diagnosis of COVID-19 is readily accomplished through a multitude of reliable testing platforms; however, prognostic prediction remains elusive. To this end, we identified a short epitope from the SARS-CoV-2 nucleocapsid protein and also a disease risk factor score based upon comorbidities and age. The presence of antibodies specifically binding to this epitope plus a score cutoff can predict severe COVID-19 outcomes with 96.7% specificity.

Bond Rotations at the Si(100) Surface: Anharmonicity, Chaotic Dynamics, and Signature of Tilted-Dimer Reconstruction

1992 ◽  
Vol 291 ◽  
Author(s):  
J. Gryko ◽  
R. E. Allen
Keyword(s):  
First Principles ◽  
Chaotic Dynamics ◽  
Rotation Angle ◽  
Chaotic Behavior ◽  
Bond Rotation ◽  
Atomic Displacements ◽  
Rotation Mode ◽  
The Fourier Transform ◽  
Dynamics Simulations ◽  
Strong Anharmonicity

ABSTRACTIn our first-principles-based molecular dynamics simulations for Si(100), we have found that the total energy U(θ) is rather flat with respect to the bond-rotation angle θ for |θ| <10°, with shallow minima at the positions θ = ± θ0 corresponding to a tilted-dimer geometry. Here we calculate the Fourier transform of the atomic displacements, u(ω), and find a characteristic bond-rotation mode with v − 5 THz. This mode is primarily associated with the upper atom in a dimer, and appears to be a signature of the tilted-dimer reconstruction. At low temperature the vibrations are nearly harmonic, but at high temperature there is strong anharmonicity, and θ appears to exhibit chaotic behavior.

AMP-activated protein kinase: new regulation, new roles?

2012 ◽  
Vol 445 (1) ◽  
pp. 11-27 ◽  
Author(s):  
David Carling ◽  
Claire Thornton ◽  
Angela Woods ◽  
Matthew J. Sanders
Keyword(s):  
Protein Kinase ◽  
Living Cells ◽  
Cellular Functions ◽  
Disease States ◽  
Kinase Cascade ◽  
Amp Activated Protein Kinase ◽  
Obesity And Cancer ◽  
Hydrolysis Of ◽  
Protein Kinase Cascade

The hydrolysis of ATP drives virtually all of the energy-requiring processes in living cells. A prerequisite of living cells is that the concentration of ATP needs to be maintained at sufficiently high levels to sustain essential cellular functions. In eukaryotic cells, the AMPK (AMP-activated protein kinase) cascade is one of the systems that have evolved to ensure that energy homoeostasis is maintained. AMPK is activated in response to a fall in ATP, and recent studies have suggested that ADP plays an important role in regulating AMPK. Once activated, AMPK phosphorylates a broad range of downstream targets, resulting in the overall effect of increasing ATP-producing pathways whilst decreasing ATP-utilizing pathways. Disturbances in energy homoeostasis underlie a number of disease states in humans, e.g. Type 2 diabetes, obesity and cancer. Reflecting its key role in energy metabolism, AMPK has emerged as a potential therapeutic target. In the present review we examine the recent progress aimed at understanding the regulation of AMPK and discuss some of the latest developments that have emerged in key areas of human physiology where AMPK is thought to play an important role.

scholarly journals PARP1 catalytic variants reveal branching and chain length-specific functions of poly(ADP-ribose) in cellular physiology and stress response

2020 ◽  
Vol 48 (18) ◽  
pp. 10015-10033 ◽  
Author(s):  
Lisa Aberle ◽  
Annika Krüger ◽  
Julia M Reber ◽  
Michelle Lippmann ◽  
Matthias Hufnagel ◽  
...  
Keyword(s):  
Chain Length ◽  
Cell Cycle Progression ◽  
Protein Localization ◽  
Biological Significance ◽  
Genotoxic Stress ◽  
Cell Physiology ◽  
Cellular Functions ◽  
Beneficial Effects ◽  
Cellular Processes ◽  
Mouse Tissues

Abstract Poly(ADP-ribosyl)ation regulates numerous cellular processes like genome maintenance and cell death, thus providing protective functions but also contributing to several pathological conditions. Poly(ADP-ribose) (PAR) molecules exhibit a remarkable heterogeneity in chain lengths and branching frequencies, but the biological significance of this is basically unknown. To unravel structure-specific functions of PAR, we used PARP1 mutants producing PAR of different qualities, i.e. short and hypobranched (PARP1\G972R), short and moderately hyperbranched (PARP1\Y986S), or strongly hyperbranched PAR (PARP1\Y986H). By reconstituting HeLa PARP1 knockout cells, we demonstrate that PARP1\G972R negatively affects cellular endpoints, such as viability, cell cycle progression and genotoxic stress resistance. In contrast, PARP1\Y986S elicits only mild effects, suggesting that PAR branching compensates for short polymer length. Interestingly, PARP1\Y986H exhibits moderate beneficial effects on cell physiology. Furthermore, different PARP1 mutants have distinct effects on molecular processes, such as gene expression and protein localization dynamics of PARP1 itself, and of its downstream factor XRCC1. Finally, the biological relevance of PAR branching is emphasized by the fact that branching frequencies vary considerably during different phases of the DNA damage-induced PARylation reaction and between different mouse tissues. Taken together, this study reveals that PAR branching and chain length essentially affect cellular functions, which further supports the notion of a ‘PAR code’.

scholarly journals Exchangeable Chaperone Modules Contribute to Specification of Type I and Type II Hsp40 Cellular Function

2004 ◽  
Vol 15 (2) ◽  
pp. 761-773 ◽  
Author(s):  
Chun-Yang Fan ◽  
Soojin Lee ◽  
Hong-Yu Ren ◽  
Douglas M. Cyr
Keyword(s):  
In Vivo Studies ◽  
Cell Physiology ◽  
Type I ◽  
Type Ii ◽  
Cellular Functions ◽  
Chaperone Function ◽  
Sequence Identity ◽  
Carboxyl Terminal ◽  
High Degree

Hsp40 family members regulate Hsp70s ability to bind nonnative polypeptides and thereby play an essential role in cell physiology. Type I and type II Hsp40s, such as yeast Ydj1 and Sis1, form chaperone pairs with cytosolic Hsp70 Ssa1 that fold proteins with different efficiencies and carry out specific cellular functions. The mechanism by which Ydj1 and Sis1 specify Hsp70 functions is not clear. Ydj1 and Sis1 share a high degree of sequence identity in their amino and carboxyl terminal ends, but each contains a structurally unique and centrally located protein module that is implicated in chaperone function. To test whether the chaperone modules of Ydj1 and Sis1 function in the specification of Hsp70 action, we constructed a set of chimeric Hsp40s in which the chaperone domains of Ydj1 and Sis1 were swapped to form YSY and SYS. Purified SYS and YSY exhibited protein-folding activity and substrate specificity that mimicked that of Ydj1 and Sis1, respectively. In in vivo studies, YSY exhibited a gain of function and, unlike Ydj1, could complement the lethal phenotype of sis1Δ and facilitate maintenance of the prion [RNQ+]. Ydj1 and Sis1 contain exchangeable chaperone modules that assist in specification of Hsp70 function.

scholarly journals Chaotic Behavior in a Switched Dynamical System

2008 ◽  
Vol 2008 ◽  
pp. 1-6 ◽  
Author(s):  
Fatima El Guezar ◽  
Hassane Bouzahir
Keyword(s):  
Hybrid Systems ◽  
Chaotic Dynamics ◽  
Chaotic Behavior ◽  
Numerical Study ◽  
Piecewise Linear ◽  
Open Loop ◽  
Buck Converter ◽  
Modeling Techniques ◽  
Scientific Laboratory ◽  
Switched Dynamical System

We present a numerical study of an example of piecewise linear systems that constitute a class of hybrid systems. Precisely, we study the chaotic dynamics of the voltage-mode controlled buck converter circuit in an open loop. By considering the voltage input as a bifurcation parameter, we observe that the obtained simulations show that the buck converter is prone to have subharmonic behavior and chaos. We also present the corresponding bifurcation diagram. Our modeling techniques are based on the new French native modeler and simulator for hybrid systems called Scicos (Scilab connected object simulator) which is a Scilab (scientific laboratory) package. The followed approach takes into account the hybrid nature of the circuit.

What Can Transgenic and Gene-targeted Mouse Models Teach Us about Salivary Gland Physiology?

2000 ◽  
Vol 14 (1) ◽  
pp. 5-11 ◽  
Author(s):  
J.E. Melvin ◽  
H.-V. Nguyen ◽  
R.L. Evans ◽  
G.E. Shull
Keyword(s):  
Salivary Gland ◽  
Mouse Models ◽  
Recombinant Dna ◽  
Genetically Modified ◽  
Cell Physiology ◽  
Specific Expression ◽  
Disease States ◽  
Salivary Gland Secretion ◽  
Genetically Modified Mice ◽  
Gland Function

Thousands of genetically modified mice have been developed since the first reports of stable expression of recombinant DNA in this species nearly 20 years ago. This mammalian model system has revolutionized the study of whole-animal, organ, and cell physiology. Transgenic and gene-targeted mice have been widely used to characterize salivary-gland-specific expression and to identify genes associated with tumorigenesis. Moreover, several of these mouse lines have proved to be useful models of salivary gland disease related to impaired immunology, i.e., Sjogren's syndrome, and disease states associated with pathogens. Despite the availability of genetically modified mice, few investigators have taken advantage of this resource to better their understanding of salivary gland function as it relates to the production of saliva. In this article, we describe the methods used to generate transgenic and gene-targeted mice and provide an overview of the advantages of and potential difficulties with these models. Finally, using these mouse models, we discuss the advances made in our understanding of the salivary gland secretion process.

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