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Article ; Online: Critical insights to COVID-19 disease and potential treatments using a systems analysis approach that integrates physiology, pharmacology, and clinical pharmacology.

Martin, Jennifer H / Head, Richard J

2022 Volume 10, Issue 1, Page(s) e00918

MeSH term(s)	COVID-19 ; Humans ; Pharmacology, Clinical ; SARS-CoV-2 ; Systems Analysis
Language	English
Publishing date	2022-02-01
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	2740389-0
ISSN	2052-1707 ; 2052-1707
ISSN (online)	2052-1707
ISSN	2052-1707
DOI	10.1002/prp2.918
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Article: COVID infection in 4 steps: Thermodynamic considerations reveal how viral mucosal diffusion, target receptor affinity and furin cleavage act in concert to drive the nature and degree of infection in human COVID-19 disease.

Popovic, Marko / Martin, Jennifer H / Head, Richard J

Heliyon

2023 Volume 9, Issue 6, Page(s) e17174

Abstract: We have developed a mechanistic model of SARS-CoV-2 and SARS-CoV infection, exploring the relationship between the viral diffusion in the mucosa and viral affinity for the angiotensin converting enzyme 2 (ACE2) target. Utilising the structural similarity ...

Abstract	We have developed a mechanistic model of SARS-CoV-2 and SARS-CoV infection, exploring the relationship between the viral diffusion in the mucosa and viral affinity for the angiotensin converting enzyme 2 (ACE2) target. Utilising the structural similarity of SARS-CoV and SARS-CoV-2 and a shared viral target receptor (ACE2), but a dramatic difference in upper or lower respiratory tract infectivity, we were able to generate insights into the linkage of mucosal diffusion and target receptor affinity in determining the pathophysiological pathways of these two viruses. Our analysis reveals that for SARS-CoV-2 the higher affinity of ACE2 binding, the faster and more complete the mucosal diffusion in its transport from the upper airway to the region of the ACE2 target on the epithelium. This diffusional process is essential for the presentation of this virus to the furin catalysed highly efficient entry and infection process in the upper respiratory tract epithelial cells. A failure of SARS-CoV to follow this path is associated with lower respiratory tract infection and decreased infectivity. Thus, our analysis supports the view that through tropism SARS-CoV-2 has evolved a highly efficient membrane entry process that can act in concert with a high binding affinity of this virus and its variants for its ACE2 which in turn promotes enhanced movement of the virus from airway to epithelium. In this way ongoing mutations yielding higher affinities of SARS-CoV-2 for the ACE2 target becomes the basis for higher upper respiratory tract infectivity and greater viral spread. It is concluded that SARS-CoV-2 is constrained in the extent of its activities by the fundamental laws of physics and thermodynamics. Laws that describe diffusion and molecular binding. Moreover it can be speculated that the very earliest contact of this virus with the human mucosa defines the pathogenesis of this infection.
Language	English
Publishing date	2023-06-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e17174
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Article ; Online: COVID infection in 4 steps

Marko Popovic / Jennifer H. Martin / Richard J. Head

Heliyon, Vol 9, Iss 6, Pp e17174- (2023)

Thermodynamic considerations reveal how viral mucosal diffusion, target receptor affinity and furin cleavage act in concert to drive the nature and degree of infection in human COVID-19 disease

2023

Abstract	We have developed a mechanistic model of SARS-CoV-2 and SARS-CoV infection, exploring the relationship between the viral diffusion in the mucosa and viral affinity for the angiotensin converting enzyme 2 (ACE2) target. Utilising the structural similarity of SARS-CoV and SARS-CoV-2 and a shared viral target receptor (ACE2), but a dramatic difference in upper or lower respiratory tract infectivity, we were able to generate insights into the linkage of mucosal diffusion and target receptor affinity in determining the pathophysiological pathways of these two viruses.Our analysis reveals that for SARS-CoV-2 the higher affinity of ACE2 binding, the faster and more complete the mucosal diffusion in its transport from the upper airway to the region of the ACE2 target on the epithelium. This diffusional process is essential for the presentation of this virus to the furin catalysed highly efficient entry and infection process in the upper respiratory tract epithelial cells. A failure of SARS-CoV to follow this path is associated with lower respiratory tract infection and decreased infectivity. Thus, our analysis supports the view that through tropism SARS-CoV-2 has evolved a highly efficient membrane entry process that can act in concert with a high binding affinity of this virus and its variants for its ACE2 which in turn promotes enhanced movement of the virus from airway to epithelium. In this way ongoing mutations yielding higher affinities of SARS-CoV-2 for the ACE2 target becomes the basis for higher upper respiratory tract infectivity and greater viral spread. It is concluded that SARS-CoV-2 is constrained in the extent of its activities by the fundamental laws of physics and thermodynamics. Laws that describe diffusion and molecular binding. Moreover it can be speculated that the very earliest contact of this virus with the human mucosa defines the pathogenesis of this infection.
Keywords	Viral diffusion ; Pharmacology ; Affinity constant ; Thermodynamics ; Human disease ; SARS-CoV2 ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	570
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Human variation in response to food and nutrients.

Head, Richard J / Buckley, Jonathan D

Nutrition reviews

2020 Volume 78, Issue 12 Suppl 2, Page(s) 49–52

Abstract: The application of science to human nutrition over the centuries has served societies well. One example is the identification of key nutrients to overcome nutritional deficiencies, which has enhanced life expectancy. Enhanced life expectancy, however, is ...

Abstract	The application of science to human nutrition over the centuries has served societies well. One example is the identification of key nutrients to overcome nutritional deficiencies, which has enhanced life expectancy. Enhanced life expectancy, however, is associated with an increased prevalence of chronic disorders related to food and nutrition. Findings of studies indicating that individual responses to nutrients differ substantially between individuals make it necessary to re-examine the relationship between nutrition and human health. The emergence of new genomic-based technologies illustrates the complexity and scale of the interactions between nutrition and genetic factors. Epigenetic modifications resulting from interactions of the genetic profile, aging, and lifestyle can influence the time course of chronic disorders and contribute to human variability in response to nutritional interventions. Developing a better understanding of human variability as it applies to human nutrition will involve embracing the approaches and principles of complex science.
MeSH term(s)	Aging ; Biological Variation, Population ; Chronic Disease ; Epigenesis, Genetic ; Food ; Genomics ; Humans ; Life Style
Language	English
Publishing date	2020-12-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	82067-2
ISSN	1753-4887 ; 0029-6643
ISSN (online)	1753-4887
ISSN	0029-6643
DOI	10.1093/nutrit/nuaa068
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Article ; Online: Obesity and COVID-19: Renin-Angiotensin as a mediator of morbidity and mortality.

Martin, Jennifer / Head, Richard

The British journal of nutrition

2021 , Page(s) 1–6

Language	English
Publishing date	2021-06-03
Publishing country	England
Document type	Journal Article
ZDB-ID	280396-3
ISSN	1475-2662 ; 0007-1145
ISSN (online)	1475-2662
ISSN	0007-1145
DOI	10.1017/S0007114521001847
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Book ; Conference proceedings ; Online: Magnetostratigraphy and biostratigraphy of ODP Leg 105 sites and DSDP Hole 12-112, supplementary data to: Baldauf, Jack G; Clement, Bradford M; Aksu, Ali E; de Vernal, Anne; Firth, John V; Hall, Frank R; Head, Martin J; Jarrard, Richard D; Kaminski, Michael A; Lazarus, David B; Monjanel, Anne-Lise; Berggren, William A; Gradstein, Felix M; Kn?ttel, Stephen; Mudie, Peta J; Russell, Merlin D Jr (1989): Magnetostratigraphic and biostratigraphic synthesis of Ocean Drilling Program Leg 105: Labrador Sea and Baffin Bay. In: Srivastava, SP; Arthur, M; Clement, B; et al. (eds.), Proceedings of the Ocean Drilling Program, Scientific Results, College Station, TX (Ocean Drilling Program), 105, 935-956

Baldauf, Jack G / Aksu, Ali E / Clement, Bradford M / Firth, John V / Hall, Frank R / Head, Martin J / Jarrard, Richard D / Kaminski, Michael A / al., et / de Vernal, Anne

1989

Abstract: During Ocean Drilling Program (ODP) Leg 105, three sites (Sites 645 through 647) were drilled in Baffin Bay and the Labrador Sea to examine the tectonic evolution and the climatic and oceanic histories of this region. Biostratigraphic and ... ...

Abstract	During Ocean Drilling Program (ODP) Leg 105, three sites (Sites 645 through 647) were drilled in Baffin Bay and the Labrador Sea to examine the tectonic evolution and the climatic and oceanic histories of this region. Biostratigraphic and magnetostratigraphic results vary at each site, while stratigraphic resolution depends on the limited abundance of marker species and the completeness of the paleomagnetic record. Because of the paucity of planktonic microfossils and the poor paleomagnetic record signatures, stratigraphic determinations at Site 645 often rely on defining minimum temporal constraints on specific samples or stratigraphic intervals. The completed stratigraphy indicates that the sedimentary sequence recovered at Site 645 is early Miocene to Holocene in age. The magnetostratigraphy and biostratigraphies are better defined at Sites 646 and 647 in the Labrador Sea. Site 646 generally contains a well-developed magnetostratigraphy and calcareous microfossil biostratigraphy. This biostratigraphy is based on calcareous nannofossils and planktonic foraminifers typical of the North Atlantic Ocean. Siliceous microfossils are also present at Site 646, but they are restricted to upper Pliocene through Holocene sediments. The stratigraphic sequence recovered at Site 646 is late Miocene to Holocene in age. Based primarily on the calcareous nannofossil stratigraphy, the sequence recovered at Site 647 consists of lower Eocene to lower Oligocene, lower Miocene, upper Miocene, and upper Pliocene through Holocene sediments. Three hiatuses are present in this sequence: the older hiatus separates lower Oligocene sediments from lower Miocene sediments, another hiatus separates lower Miocene sediments from upper Miocene sediments, and the youngest one separates upper Miocene from upper Pliocene sediments. A magnetostratigraphy is defined for the interval from the Gauss/Matuyama boundary through the Brunhes (Clement et al., this volume). Both planktonic foraminifers and siliceous microfossils have restricted occurrences. Planktonic foraminifers occur in Pliocene and younger sediments, and siliceous microfossils are present in lower Miocene and lower Oligocene sediments. The near-continuous Eocene through lower Oligocene sequence recovered at Site 647 allows the calcareous nannofossils and diatom stratigraphies at this site to act as a Paleogene stratigraphic framework. This framework can be compared with the stratigraphy previously completed for DSDP Site 112.
Language	English
Dates of publication	1989-9999
Size	Online-Ressource
Publisher	PANGAEA - Data Publisher for Earth & Environmental Science
Publishing place	Bremen/Bremerhaven
Document type	Book ; Conference proceedings ; Online
Note	This dataset is supplement to doi:10.2973/odp.proc.sr.105.165.1989
DOI	10.1594/PANGAEA.745399
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Article ; Online: Integration of population genetics with oceanographic models reveals strong connectivity among coral reefs across Seychelles.

Burt, April J / Vogt-Vincent, Noam / Johnson, Helen / Sendell-Price, Ashley / Kelly, Steve / Clegg, Sonya M / Head, Catherine / Bunbury, Nancy / Fleischer-Dogley, Frauke / Jeremie, Marie-May / Khan, Nasreen / Baxter, Richard / Gendron, Gilberte / Mason-Parker, Christophe / Walton, Rowana / Turnbull, Lindsay A

Scientific reports

2024 Volume 14, Issue 1, Page(s) 4936

Abstract: Many countries with tropical reef systems face hard choices preserving coral reefs in the face of climate change on limited budgets. One approach to maximising regional reef resilience is targeting management efforts and resources at reefs that export ... ...

Abstract	Many countries with tropical reef systems face hard choices preserving coral reefs in the face of climate change on limited budgets. One approach to maximising regional reef resilience is targeting management efforts and resources at reefs that export large numbers of larvae to other reefs. However, this requires reef connectivity to be quantified. To map coral connectivity in the Seychelles reef system we carried out a population genomic study of the Porites lutea species complex using 241 sequenced colonies from multiple islands. To identify oceanographic drivers of this connectivity and quantify variability, we further used a 2 km resolution regional ocean simulation coupled with a larval dispersal model to predict the flow of coral larvae between reef sites. Patterns of admixture and gene flow are broadly supported by model predictions, but the realised connectivity is greater than that predicted from model simulations. Both methods detected a biogeographic dispersal barrier between the Inner and Outer Islands of Seychelles. However, this barrier is permeable and substantial larval transport is possible across Seychelles, particularly for one of two putative species found in our genomic study. The broad agreement between predicted connectivity and observed genetic patterns supports the use of such larval dispersal simulations in reef system management in Seychelles and the wider region.
MeSH term(s)	Animals ; Coral Reefs ; Seychelles ; Anthozoa/genetics ; Genetics, Population ; Larva
Language	English
Publishing date	2024-03-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-55459-x
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Article ; Online: The interacting physiology of COVID-19 and the renin-angiotensin-aldosterone system: Key agents for treatment.

Lumbers, Eugenie R / Head, Richard / Smith, Gary R / Delforce, Sarah J / Jarrott, Bevyn / H Martin, Jennifer / Pringle, Kirsty G

Pharmacology research & perspectives

2022 Volume 10, Issue 1, Page(s) e00917

Abstract: SARS-CoV-2 interacting with its receptor, angiotensin-converting enzyme 2 (ACE2), turns the host response to viral infection into a dysregulated uncontrolled inflammatory response. This is because ACE2 limits the production of the peptide angiotensin II ( ...

Abstract	SARS-CoV-2 interacting with its receptor, angiotensin-converting enzyme 2 (ACE2), turns the host response to viral infection into a dysregulated uncontrolled inflammatory response. This is because ACE2 limits the production of the peptide angiotensin II (Ang II) and SARS-CoV-2, through the destruction of ACE2, allows the uncontrolled production of Ang II. Recovery from trauma requires activation of both a tissue response to injury and activation of a whole-body response to maintain tissue perfusion. Tissue and circulating renin-angiotensin systems (RASs) play an essential role in the host response to infection and injury because of the actions of Ang II, mediated via its AT
MeSH term(s)	Angiotensin Receptor Antagonists/therapeutic use ; Angiotensin-Converting Enzyme 2/physiology ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; COVID-19/drug therapy ; COVID-19/etiology ; Drug Repositioning ; Humans ; Inflammation/etiology ; Renin/antagonists & inhibitors ; Renin-Angiotensin System/physiology ; SARS-CoV-2/physiology
Chemical Substances	Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Renin (EC 3.4.23.15)
Language	English
Publishing date	2022-02-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2740389-0
ISSN	2052-1707 ; 2052-1707
ISSN (online)	2052-1707
ISSN	2052-1707
DOI	10.1002/prp2.917
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Article ; Online: Systems analysis shows that thermodynamic physiological and pharmacological fundamentals drive COVID-19 and response to treatment.

Head, Richard J / Lumbers, Eugenie R / Jarrott, Bevyn / Tretter, Felix / Smith, Gary / Pringle, Kirsty G / Islam, Saiful / Martin, Jennifer H

Pharmacology research & perspectives

2022 Volume 10, Issue 1, Page(s) e00922

Abstract: Why a systems analysis view of this pandemic? The current pandemic has inflicted almost unimaginable grief, sorrow, loss, and terror at a global scale. One of the great ironies with the COVID-19 pandemic, particularly early on, is counter intuitive. The ... ...

Abstract	Why a systems analysis view of this pandemic? The current pandemic has inflicted almost unimaginable grief, sorrow, loss, and terror at a global scale. One of the great ironies with the COVID-19 pandemic, particularly early on, is counter intuitive. The speed at which specialized basic and clinical sciences described the details of the damage to humans in COVID-19 disease has been impressive. Equally, the development of vaccines in an amazingly short time interval has been extraordinary. However, what has been less well understood has been the fundamental elements that underpin the progression of COVID-19 in an individual and in populations. We have used systems analysis approaches with human physiology and pharmacology to explore the fundamental underpinnings of COVID-19 disease. Pharmacology powerfully captures the thermodynamic characteristics of molecular binding with an exogenous entity such as a virus and its consequences on the living processes well described by human physiology. Thus, we have documented the passage of SARS-CoV-2 from infection of a single cell to species jump, to tropism, variant emergence and widespread population infection. During the course of this review, the recurrent observation was the efficiency and simplicity of one critical function of this virus. The lethality of SARS-CoV-2 is due primarily to its ability to possess and use a variable surface for binding to a specific human target with high affinity. This binding liberates Gibbs free energy (GFE) such that it satisfies the criteria for thermodynamic spontaneity. Its binding is the prelude to human host cellular entry and replication by the appropriation of host cell constituent molecules that have been produced with a prior energy investment by the host cell. It is also a binding that permits viral tropism to lead to high levels of distribution across populations with newly formed virions. This thermodynamic spontaneity is repeated endlessly as infection of a single host cell spreads to bystander cells, to tissues, to humans in close proximity and then to global populations. The principal antagonism of this process comes from SARS-CoV-2 itself, with its relentless changing of its viral surface configuration, associated with the inevitable emergence of variants better configured to resist immune sequestration and importantly with a greater affinity for the host target and higher infectivity. The great value of this physiological and pharmacological perspective is that it reveals the fundamental thermodynamic underpinnings of SARS-CoV-2 infection.
MeSH term(s)	Animals ; COVID-19/drug therapy ; COVID-19/etiology ; Chiroptera/virology ; Humans ; Inflammasomes/physiology ; Nasopharynx/virology ; SARS-CoV-2/physiology ; Systems Analysis ; Thermodynamics ; Viral Tropism ; Virus Internalization
Chemical Substances	Inflammasomes
Language	English
Publishing date	2022-02-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2740389-0
ISSN	2052-1707 ; 2052-1707
ISSN (online)	2052-1707
ISSN	2052-1707
DOI	10.1002/prp2.922
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Article ; Online: Corrigendum: The Vacc-SeqQC project: Benchmarking RNA-Seq for clinical vaccine studies.

Goll, Johannes B / Bosinger, Steven E / Jensen, Travis L / Walum, Hasse / Grimes, Tyler / Tharp, Gregory K / Natrajan, Muktha S / Blazevic, Azra / Head, Richard D / Gelber, Casey E / Steenbergen, Kristen J / Patel, Nirav B / Sanz, Patrick / Rouphael, Nadine G / Anderson, Evan J / Mulligan, Mark J / Hoft, Daniel F

Frontiers in immunology

2023 Volume 14, Page(s) 1163550

Abstract: This corrects the article DOI: 10.3389/fimmu.2022.1093242.]. ...

Abstract	[This corrects the article DOI: 10.3389/fimmu.2022.1093242.].
Language	English
Publishing date	2023-02-23
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1163550
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