LIVIVO - Search results -

Search results

Result 1 - 10 of total 74

Search options

Article ; Online: A new synergistic model for simulating exercise incorporating control mechanisms at cellular and organ scales.

Pearce, Nicholas F / Kim, Eun-Jin

2023 Volume 163, Page(s) 107141

Abstract: The physiological response of the cardio-vascular system (CVS) to physical activity is of great importance to those working in sporting research and has profound consequences for the health and well-being of people. Coronary vasodilation and the ... ...

Abstract	The physiological response of the cardio-vascular system (CVS) to physical activity is of great importance to those working in sporting research and has profound consequences for the health and well-being of people. Coronary vasodilation and the physiological mechanisms involved in exercise have frequently been the focus of numerical models for simulating exercise. This is partly achieved using the time-varying-elastance (TVE) theory, which prescribes the pressure-volume relationship of the ventricle as a periodic function of time, tuned using empirical data. The empirical foundations of the TVE method however, and its suitability for CVS modelling are frequently questioned. To overcome this challenge, we adopt a different synergistic approach in which a model for the microscale heart muscle (myofibers) activity is embedded within a macro organ-scale CVS model. We developed such a synergistic model by including the coronary flow and various control mechanisms at the circulation level through feedback and feedforward means, and at the microscale (contractile) through the regulation of ATP availability and myofiber force depending on exercise intensity or heart rate. The coronary flow produced by the model displays the well-known 2-phase character of the flow, which is preserved under exercise. The model is tested by simulating reactive hyperemia, which is a transient occlusion of the coronary flow, successfully reproducing the additional coronary flow following the block removal. On-transient exercise results reveal a rise in both cardiac output and mean ventricle pressure as expected. The stroke volume increases initially, but then declines during the latter period of HR rise, corresponding with one of the main physiological responses to exercise. The pressure-volume loop expands during exercise, as systolic pressure rises. The Myocardial oxygen demand increases during exercise and the coronary blood supply increases in response, causing an excess of oxygen supply to the heart. Off-transient exercise recovery is largely a reverse of this response, although the behaviour is slightly more varied, with sudden spikes in coronary resistance. Different levels of fitness and exercise intensity are tested and reveal that the stroke volume rises until a level of myocardial oxygen demand is reached at which point it declines. This level of demand is independent of fitness or exercise intensity. An advantage of our model is demonstrated in the correspondence between the micro and organ scale mechanics so that cellular pathologies can be traced from exercise performance with relatively little computational or experimental expense.
MeSH term(s)	Humans ; Coronary Circulation/physiology ; Exercise ; Myocardium ; Blood Pressure ; Oxygen
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2023-06-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	127557-4
ISSN	1879-0534 ; 0010-4825
ISSN (online)	1879-0534
ISSN	0010-4825
DOI	10.1016/j.compbiomed.2023.107141
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 653: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article: An Investigation of Left Ventricular Valve Disorders and the Mechano-Electric Feedback Using a Synergistic Lumped Parameter Cardiovascular Numerical Model.

Pearce, Nicholas / Kim, Eun-Jin

Bioengineering (Basel, Switzerland)

2022 Volume 9, Issue 9

Abstract: Cardiac diseases and failure make up one of largest contributions to global mortality and significantly detriment the quality of life for millions of others. Disorders in the valves of the left ventricle are a prominent example of heart disease, with ... ...

Abstract	Cardiac diseases and failure make up one of largest contributions to global mortality and significantly detriment the quality of life for millions of others. Disorders in the valves of the left ventricle are a prominent example of heart disease, with prolapse, regurgitation, and stenoses-the three main valve disorders. It is widely known that mitral valve prolapse increases the susceptibility to cardiac arrhythmia. Here, we investigate stenoses and regurgitation of the mitral and aortic valves in the left ventricle using a synergistic low-order numerical model. The model synergy derives from the incorporation of the mechanical, chemical, and electrical elements. As an alternative framework to the time-varying elastance (TVE) method, it allows feedback mechanisms at work in the heart to be considered. The TVE model imposes the ventricular pressure-volume relationship using a periodic function rather than calculating it consistently. Using our synergistic approach, the effects of valve disorders on the mechano-electric-feedback (MEF) are investigated. The MEF is the influence of cellular mechanics on the electrical activity, and significantly contributes to the generation of arrhythmia. We further investigate stenoses and regurgitation of the mitral and aortic valves and their relationship with the MEF and generation of arrhythmia. Mitral valve stenosis is found to increase the sensitivity to arrhythmia-stimulating systolic stretch, and reduces the sensitivity to diastolic stretch. Aortic valve stenosis does not change the sensitivity to arrhythmia-stimulating stretch, and regurgitation reduces it. A key result is found when valve regurgitation is accompanied by diastolic stretch. In the presence of MEF disorder, ectopic beats become far more frequent when accompanied by valve regurgitation. Therefore, arrhythmia resulting from a disorder in the MEF will be more severe when valve regurgitation is present.
Language	English
Publishing date	2022-09-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2746191-9
ISSN	2306-5354
ISSN	2306-5354
DOI	10.3390/bioengineering9090454
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: A method for intuitively extracting macromolecular dynamics from structural disorder.

Pearce, Nicholas M / Gros, Piet

Nature communications

2021 Volume 12, Issue 1, Page(s) 5493

Abstract: Macromolecular dynamics manifest as disorder in structure determination, which is subsequently accounted for by displacement parameters (also called temperature factors, or B-factors) or alternate conformations. Though B-factors contain detailed ... ...

Abstract	Macromolecular dynamics manifest as disorder in structure determination, which is subsequently accounted for by displacement parameters (also called temperature factors, or B-factors) or alternate conformations. Though B-factors contain detailed information about structural dynamics, they are the total of multiple sources of disorder, making them difficult to interpret and thus little-used in structural analysis. We report here an analytical approach for decomposing molecular disorder into a parsimonious hierarchical series of contributions, providing an intuitive basis for quantitative structural-dynamics analysis. We demonstrate the decomposition of disorder on example SARS-CoV-2 and STEAP4 structures, from both crystallographic and cryo-electron microscopy data, and reveal how understanding of the macromolecular disorder leads to deeper understanding of molecular motions and flexibility, and suggests hypotheses for molecular mechanisms.
MeSH term(s)	COVID-19 ; Coronavirus 3C Proteases/chemistry ; Cryoelectron Microscopy ; Humans ; Macromolecular Substances/chemistry ; Membrane Proteins/chemistry ; Molecular Dynamics Simulation ; Oxidoreductases/chemistry ; Protein Conformation ; SARS-CoV-2/enzymology
Chemical Substances	Macromolecular Substances ; Membrane Proteins ; Oxidoreductases (EC 1.-) ; STEAP4 protein, human (EC 1.16.1.-) ; 3C-like proteinase, SARS-CoV-2 (EC 3.4.22.-) ; Coronavirus 3C Proteases (EC 3.4.22.28)
Language	English
Publishing date	2021-09-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-25814-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Modelling the cardiac response to a mechanical stimulation using a low-order model of the heart.

Pearce, Nicholas / Kim, Eun-Jin

Mathematical biosciences and engineering : MBE

2021 Volume 18, Issue 4, Page(s) 4871–4893

Abstract: Heart diseases are one of the leading causes of death worldwide, and a dysfunction of the cardiac electrical mechanisms is responsible for a significant portion of these deaths. One of these mechanisms, the mechano-electric feedback (MEF), is the ... ...

Abstract	Heart diseases are one of the leading causes of death worldwide, and a dysfunction of the cardiac electrical mechanisms is responsible for a significant portion of these deaths. One of these mechanisms, the mechano-electric feedback (MEF), is the electrical response of the heart to local mechanical changes in the environment. This electrical response, in turn, leads to macroscopic changes in heart function. In this paper, we demonstrate that the MEF plays a crucial role in mechanical generation and recovery from arrhythmia which has been observed in experimental studies. To this end, we investigate the cardiac response to a mechanical stimulation using a minimal, multiscale model of the heart which couples the organ level dynamics (left ventricular pressure and volume) and contractile dynamics. By including a mechanical stimulation into the model as a (short, sudden) impulse in the muscle microscale stress, we investigate how the timing, amplitude and duration of the impulse affect the cardiac cycle. In particular, when introduced in the diastolic period of the cardiac cycle, the pulse rate can be stabilised, and ectopic beats and bifurcation can be eliminated, either temporarily or permanently. The stimulation amplitude is a key indicator to this response. We find an optimal value of the impulse amplitude above or below which the impulse maximises the stabilisation. As a result a dysfunction of the MEF can be helped using a mechanical stimulation, by allowing the heart to recover its pumping power. On the other hand, when the mechanical stimulation is introduced towards the end of systole, arrhythmia can be generated.
MeSH term(s)	Arrhythmias, Cardiac ; Feedback ; Heart ; Heart Rate ; Humans
Language	English
Publishing date	2021-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2265126-3
ISSN	1551-0018 ; 1551-0018
ISSN (online)	1551-0018
ISSN	1551-0018
DOI	10.3934/mbe.2021248
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Development of a novel low-order model for atrial function and a study of atrial mechano-electric feedback.

Pearce, Nicholas F / Turner, Mark C / Maddock, Helen L / Kim, Eun-Jin

Computers in biology and medicine

2023 Volume 159, Page(s) 106697

Abstract: Numerical models of the cardiovascular system have largely focused on the function of the ventricles, with atrial function often neglected. Furthermore, the time-varying elastance method that prescribes the pressure-volume relationship rather than ... ...

Abstract	Numerical models of the cardiovascular system have largely focused on the function of the ventricles, with atrial function often neglected. Furthermore, the time-varying elastance method that prescribes the pressure-volume relationship rather than calculating it consistently is frequently used for the ventricles and atrium. This method has yet to be validated however, so its applicability for cardiac modelling is frequently questioned. To overcome this challenge, we propose a synergistic model of left atrium (LA) and left ventricle (LV) by self-consistently integrating various feedback mechanisms among the electro-mechanical and chemical functions of the micro-scale myofiber, the macro-scale dynamics of the LA and LV, the atrioventricular node (AV), and circulation. The model is tested and shown to reproduce the essential features of the atrium cycling, such as the characteristic figure of eight pressure-volume loops. Our model is further developed to investigate the effect of dysfunctions of the mechanical-electric feedback (MEF) in the atrium. Our model not only successfully reproduces key experimental MEF observations such as prolonged action-potential and increases in action-potential magnitude induced by atrial stretch but also shows how MEF and arrhythmia of the atrium lead to a degradation of cardiac output and pumping power with significant consequences. In particular, MEF reproduces arrhythmia such as ectopic and erratic cycling, missed heart beats and restricted function.
MeSH term(s)	Feedback, Physiological ; Models, Cardiovascular ; Atrial Function, Left ; Heart Atria ; Heart Ventricles ; Ventricular Function, Left ; Electrophysiological Phenomena ; Mechanical Phenomena ; Humans
Language	English
Publishing date	2023-02-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	127557-4
ISSN	1879-0534 ; 0010-4825
ISSN (online)	1879-0534
ISSN	0010-4825
DOI	10.1016/j.compbiomed.2023.106697
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 653: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Experiences From Developing Software for Large X-Ray Crystallography-Driven Protein-Ligand Studies.

Pearce, Nicholas M / Skyner, Rachael / Krojer, Tobias

Frontiers in molecular biosciences

2022 Volume 9, Page(s) 861491

Abstract: The throughput of macromolecular X-ray crystallography experiments has surged over the last decade. This remarkable gain in efficiency has been facilitated by increases in the availability of high-intensity X-ray beams, (ultra)fast detectors and high ... ...

Abstract	The throughput of macromolecular X-ray crystallography experiments has surged over the last decade. This remarkable gain in efficiency has been facilitated by increases in the availability of high-intensity X-ray beams, (ultra)fast detectors and high degrees of automation. These developments have in turn spurred the development of several dedicated centers for crystal-based fragment screening which enable the preparation and collection of hundreds of single-crystal diffraction datasets per day. Crystal structures of target proteins in complex with small-molecule ligands are of immense importance for structure-based drug design (SBDD) and their rapid turnover is a prerequisite for accelerated development cycles. While the experimental part of the process is well defined and has by now been established at several synchrotron sites, it is noticeable that software and algorithmic aspects have received far less attention, as well as the implications of new methodologies on established paradigms for structure determination, analysis, and visualization. We will review three key areas of development of large-scale protein-ligand studies. First, we will look into new software developments for batch data processing, followed by a discussion of the methodological changes in the analysis, modeling, refinement and deposition of structures for SBDD, and the changes in mindset that these new methods require, both on the side of depositors and users of macromolecular models. Finally, we will highlight key new developments for the presentation and analysis of the collections of structures that these experiments produce, and provide an outlook for future developments.
Language	English
Publishing date	2022-04-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2022.861491
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: per

Pearce, Nicholas / Davies, E Stephen / Champness, Neil R

Molecules (Basel, Switzerland)

2020 Volume 25, Issue 7

Abstract: 1,4-dimethoxypillar[5]arene undergoes reversible multielectron oxidations forming stable radical cations, a property retained when incorporated in [2]rotaxanes, suggesting that pillar[5]arenes can be employed as viable, yet unreported, electron donors. ...

Abstract	1,4-dimethoxypillar[5]arene undergoes reversible multielectron oxidations forming stable radical cations, a property retained when incorporated in [2]rotaxanes, suggesting that pillar[5]arenes can be employed as viable, yet unreported, electron donors.
MeSH term(s)	Calixarenes/chemistry ; Electrochemical Techniques ; Molecular Structure ; Rotaxanes/chemistry
Chemical Substances	Rotaxanes ; pillar(5)arene ; Calixarenes (130036-26-9)
Language	English
Publishing date	2020-04-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules25071627
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.MO 81: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Improving sampling of crystallographic disorder in ensemble refinement.

Ploscariu, Nicoleta / Burnley, Tom / Gros, Piet / Pearce, Nicholas M

Acta crystallographica. Section D, Structural biology

2021 Volume 77, Issue Pt 11, Page(s) 1357–1364

Abstract: Ensemble refinement, the application of molecular dynamics to crystallographic refinement, explicitly models the disorder inherent in macromolecular structures. These ensemble models have been shown to produce more accurate structures than traditional ... ...

Abstract	Ensemble refinement, the application of molecular dynamics to crystallographic refinement, explicitly models the disorder inherent in macromolecular structures. These ensemble models have been shown to produce more accurate structures than traditional single-model structures. However, suboptimal sampling of the molecular-dynamics simulation and modelling of crystallographic disorder has limited the utility of the method, and can lead to unphysical and strained models. Here, two improvements to the ensemble refinement method implemented within Phenix are presented: DEN restraints, which guide the local sampling of conformations and allow a more robust exploration of local conformational landscapes, and ECHT disorder models, which allow the selection of more physically meaningful and effective disorder models for parameterizing the continuous disorder components within a crystal. These improvements lead to more consistent and physically interpretable simulations of macromolecules in crystals, and allow structural heterogeneity and disorder to be systematically explored on different scales. The new approach is demonstrated on several case studies and the SARS-CoV-2 main protease, and demonstrates how the choice of disorder model affects the type of disorder that is sampled by the restrained molecular-dynamics simulation.
MeSH term(s)	Coronavirus 3C Proteases/chemistry ; Crystallography, X-Ray ; Humans ; Molecular Dynamics Simulation ; SARS-CoV-2/enzymology
Chemical Substances	3C-like proteinase, SARS-CoV-2 (EC 3.4.22.-) ; Coronavirus 3C Proteases (EC 3.4.22.28)
Language	English
Publishing date	2021-10-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2968623-4
ISSN	2059-7983 ; 0907-4449
ISSN (online)	2059-7983
ISSN	0907-4449
DOI	10.1107/S2059798321010044
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Details ▾
- Full text online
- Order with fees

Article: Covalent bicyclization of protein complexes yields durable quaternary structures.

Hutchins, George H / Kiehstaller, Sebastian / Poc, Pascal / Lewis, Abigail H / Oh, Jisun / Sadighi, Raya / Pearce, Nicholas M / Ibrahim, Mohamed / Drienovská, Ivana / Rijs, Anouk M / Neubacher, Saskia / Hennig, Sven / Grossmann, Tom N

Chem

2024 Volume 10, Issue 2, Page(s) 615–627

Abstract: Proteins are essential biomolecules and central to biotechnological applications. In many cases, assembly into higher-order structures is a prerequisite for protein function. Under conditions relevant for applications, protein integrity is often ... ...

Abstract	Proteins are essential biomolecules and central to biotechnological applications. In many cases, assembly into higher-order structures is a prerequisite for protein function. Under conditions relevant for applications, protein integrity is often challenged, resulting in disassembly, aggregation, and loss of function. The stabilization of quaternary structure has proven challenging, particularly for trimeric and higher-order complexes, given the complexity of involved inter- and intramolecular interaction networks. Here, we describe the chemical bicyclization of homotrimeric protein complexes, thereby increasing protein resistance toward thermal and chemical stress. This approach involves the structure-based selection of cross-linking sites, their variation to cysteine, and a subsequent reaction with a triselectrophilic agent to form a protein assembly with bicyclic topology. Besides overall increased stability, we observe resistance toward aggregation and greatly prolonged shelf life. This bicyclization strategy gives rise to unprecedented protein chain topologies and can enable new biotechnological and biomedical applications.
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2869032-1
ISSN	2451-9294 ; 2451-9294 ; 2451-9308
ISSN (online)	2451-9294
ISSN	2451-9294 ; 2451-9308
DOI	10.1016/j.chempr.2023.10.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: The Carpathian obsidians – Contribution to their FT dating and provenance (Zemplín, Slovakia)

Kohút, Milan / Westgate, John A / Pearce, Nicholas J.G / Bačo, Pavel

Journal of archaeological science: Reports. 2021 June, v. 37

2021

Abstract: The Carpathian obsidian samples from the Slovakian part of the Zemplín – Tokaj area have been studied by means of fission-track dating (FT) and geochemistry to better understand the provenance of the archaeological obsidians from the Central Europe realm. ...

Abstract	The Carpathian obsidian samples from the Slovakian part of the Zemplín – Tokaj area have been studied by means of fission-track dating (FT) and geochemistry to better understand the provenance of the archaeological obsidians from the Central Europe realm. New FT obsidian ages obtained by the isothermal plateau method (ITPFT) are in a narrow time interval between 12.45 ± 0.45 and 11.62 ± 0.25 Ma, and indicate a short-time monogenic volcanic evolution rather than a long-lasting volcanism over the 16–10 Ma period, as was previously thought. Geochemically, these obsidians belong to the silica-rich, peraluminous, high-potassium, calc-alkaline rhyolite series volcanic rocks with a ferroan character which were derived by multi-stage magmatic processes from mixed mantle and crustal sources during subduction in a volcanic arc tectonic setting. Chemical composition of the Carpathian obsidians clearly exhibits a common similarity among all examined localities (Brehov, Cejkov, Hraň, and Viničky). A comprehensive provenance study, including physical properties of the obsidians, confirms a general congruence within the studied obsidians and the use of common provenance labelling, such as Carpathian-1 (C1) for the Slovakian – Zemplín area obsidians, is recommended.
Keywords	archaeology ; chemical composition ; evolution ; geochemistry ; provenance ; subduction ; tectonics ; volcanic activity ; Central European region ; Slovakia
Language	English
Dates of publication	2021-06
Publishing place	Elsevier Ltd
Document type	Article
ISSN	2352-409X
DOI	10.1016/j.jasrep.2021.102861
Database	NAL-Catalogue (AGRICOLA)

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED