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Book: Apoptosis

Wyllie, Andrew H.

(British medical bulletin ; 53,3)

1997

Author's details	scient. ed. Andrew H. Wyllie
Series title	British medical bulletin ; 53,3
Collection
Keywords	Apoptosis ; Fetus ; Umweltfaktor ; Spätschaden ; Kleinstkind ; Fehlernährung
Subject	Fötus ; Apoptose ; Programmierter Zelltod ; Spätfolgen ; Falsche Ernährung ; Kind ; Umwelteinfluss ; Ökologischer Faktor ; Exogener Faktor ; Standortbedingungen ; Standortfaktor
Language	English
Size	IV S., S. 451 - 693 S. : Ill., graph. Darst.
Publisher	Royal Soc. of Med. Pr
Publishing place	London u.a.
Publishing country	Great Britain
Document type	Book
HBZ-ID	HT007718700
ISBN	1-85315-317-6 ; 978-1-85315-317-4
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: "Where, O death, is thy sting?" A brief review of apoptosis biology.

Wyllie, Andrew H

Molecular neurobiology

2010 Volume 42, Issue 1, Page(s) 4–9

Abstract: Apoptosis was a term introduced in 1972 to distinguish a mode of cell death with characteristic morphology and apparently regulated, endogenously driven mechanisms. The effector processes responsible for apoptosis are now mostly well known, involving ... ...

Abstract	Apoptosis was a term introduced in 1972 to distinguish a mode of cell death with characteristic morphology and apparently regulated, endogenously driven mechanisms. The effector processes responsible for apoptosis are now mostly well known, involving activation of caspases and Bcl2 family members in response to a wide variety of physiological and injury-induced signals. The factors that lead of the decision to activate apoptosis as opposed to adaptive responses to such signals (e.g. autophagy, cycle arrest, protein synthesis shutoff) are less well understood, but the intranuclear Promyelocytic Leukaemia Body (PML body) may create a local microenvironment in which the audit of DNA damage may occur, informed by the extent of the damage, the adequacy of its repair and other aspects of cell status.
MeSH term(s)	Animals ; Apoptosis/physiology ; Caspases/metabolism ; Cell Survival ; DNA Damage ; Enzyme Activation ; Humans ; Proto-Oncogene Proteins c-bcl-2/metabolism
Chemical Substances	Proto-Oncogene Proteins c-bcl-2 ; Caspases (EC 3.4.22.-)
Language	English
Publishing date	2010-06-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-010-8125-5
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Article: “Where, O Death, Is Thy Sting?” A Brief Review of Apoptosis Biology

Wyllie, Andrew H

Molecular neurobiology. 2010 Aug., v. 42, no. 1

2010

Abstract	Apoptosis was a term introduced in 1972 to distinguish a mode of cell death with characteristic morphology and apparently regulated, endogenously driven mechanisms. The effector processes responsible for apoptosis are now mostly well known, involving activation of caspases and Bcl2 family members in response to a wide variety of physiological and injury-induced signals. The factors that lead of the decision to activate apoptosis as opposed to adaptive responses to such signals (e.g. autophagy, cycle arrest, protein synthesis shutoff) are less well understood, but the intranuclear Promyelocytic Leukaemia Body (PML body) may create a local microenvironment in which the audit of DNA damage may occur, informed by the extent of the damage, the adequacy of its repair and other aspects of cell status.
Keywords	cell death ; DNA
Language	English
Dates of publication	2010-08
Size	p. 4-9.
Publisher	Humana Press Inc
Publishing place	New York
Document type	Article
ZDB-ID	645020-9
ISSN	1559-1182 ; 0893-7648
ISSN (online)	1559-1182
ISSN	0893-7648
DOI	10.1007/s12035-010-8125-5
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Article ; Online: Development of a 2,4-Diaminothiazole Series for the Treatment of Human African Trypanosomiasis Highlights the Importance of Static-Cidal Screening of Analogues.

Journal of medicinal chemistry

2023 Volume 66, Issue 13, Page(s) 8896–8916

Abstract: While treatment options for human African trypanosomiasis (HAT) have improved significantly, there is still a need for new drugs with eradication now a realistic possibility. Here, we report the development of 2,4-diaminothiazoles that demonstrate ... ...

Abstract	While treatment options for human African trypanosomiasis (HAT) have improved significantly, there is still a need for new drugs with eradication now a realistic possibility. Here, we report the development of 2,4-diaminothiazoles that demonstrate significant potency against
MeSH term(s)	Animals ; Humans ; Trypanosomiasis, African/drug therapy ; Trypanocidal Agents/therapeutic use ; Trypanocidal Agents/pharmacokinetics ; Cytostatic Agents/therapeutic use ; Trypanosoma brucei brucei ; Blood-Brain Barrier
Chemical Substances	Trypanocidal Agents ; Cytostatic Agents
Language	English
Publishing date	2023-06-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.3c00509
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Article ; Online: Combining viral genomics and clinical data to assess risk factors for severe COVID-19 (mortality, ICU admission, or intubation) amongst hospital patients in a large acute UK NHS hospital Trust.

PloS one

2023 Volume 18, Issue 3, Page(s) e0283447

Abstract: Throughout the COVID-19 pandemic, valuable datasets have been collected on the effects of the virus SARS-CoV-2. In this study, we combined whole genome sequencing data with clinical data (including clinical outcomes, demographics, comorbidity, treatment ... ...

Abstract	Throughout the COVID-19 pandemic, valuable datasets have been collected on the effects of the virus SARS-CoV-2. In this study, we combined whole genome sequencing data with clinical data (including clinical outcomes, demographics, comorbidity, treatment information) for 929 patient cases seen at a large UK hospital Trust between March 2020 and May 2021. We identified associations between acute physiological status and three measures of disease severity; admission to the intensive care unit (ICU), requirement for intubation, and mortality. Whilst the maximum National Early Warning Score (NEWS2) was moderately associated with severe COVID-19 (A = 0.48), the admission NEWS2 was only weakly associated (A = 0.17), suggesting it is ineffective as an early predictor of severity. Patient outcome was weakly associated with myriad factors linked to acute physiological status and human genetics, including age, sex and pre-existing conditions. Overall, we found no significant links between viral genomics and severe outcomes, but saw evidence that variant subtype may impact relative risk for certain sub-populations. Specific mutations of SARS-CoV-2 appear to have little impact on overall severity risk in these data, suggesting that emerging SARS-CoV-2 variants do not result in more severe patient outcomes. However, our results show that determining a causal relationship between mutations and severe COVID-19 in the viral genome is challenging. Whilst improved understanding of the evolution of SARS-CoV-2 has been achieved through genomics, few studies on how these evolutionary changes impact on clinical outcomes have been seen due to complexities associated with data linkage. By combining viral genomics with patient records in a large acute UK hospital, this study represents a significant resource for understanding risk factors associated with COVID-19 severity. However, further understanding will likely arise from studies of the role of host genetics on disease progression.
MeSH term(s)	Humans ; COVID-19/epidemiology ; SARS-CoV-2/genetics ; Pandemics ; State Medicine ; Trust ; Intensive Care Units ; Risk Factors ; Hospitals ; Intubation, Intratracheal ; United Kingdom/epidemiology
Language	English
Publishing date	2023-03-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0283447
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Article ; Online: The risk of reverse zoonotic transmission to pet animals during the current global monkeypox outbreak, United Kingdom, June to mid-September 2022.

Shepherd, Wendi / Beard, Philippa M / Brookes, Sharon M / Frost, Andrew / Roberts, Helen / Russell, Katherine / Wyllie, Steve

Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin

2022 Volume 27, Issue 39

Abstract: We report results of surveillance between June and mid-September 2022 of pet animals living in households of confirmed human monkeypox (MPX) cases. Since surveillance commenced, 154 animals from 40 households with a confirmed human MPX case were reported ...

Abstract	We report results of surveillance between June and mid-September 2022 of pet animals living in households of confirmed human monkeypox (MPX) cases. Since surveillance commenced, 154 animals from 40 households with a confirmed human MPX case were reported to the United Kingdom Animal and Plant Health Agency. No animals with clinical signs of MPX were identified. While a risk of transmission exists to pets from owners with a confirmed MPX virus infection, we assess this risk to be low.
MeSH term(s)	Disease Outbreaks/veterinary ; Humans ; Mpox (monkeypox)/diagnosis ; Mpox (monkeypox)/epidemiology ; Mpox (monkeypox)/veterinary ; Monkeypox virus ; United Kingdom/epidemiology
Language	English
Publishing date	2022-10-20
Publishing country	Sweden
Document type	Journal Article
ZDB-ID	1338803-4
ISSN	1560-7917 ; 1025-496X
ISSN (online)	1560-7917
ISSN	1025-496X
DOI	10.2807/1560-7917.ES.2022.27.39.2200758
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Article: E2F1 selects tumour cells for both life and death.

Wyllie, Andrew H

The Journal of pathology

2002 Volume 198, Issue 2, Page(s) 139–141

Abstract: E2F1 is a transcription factor involved in both cell cycle progression and apoptosis. Perhaps surprisingly, these two processes are closely related, and the choice between them appears to be made on the basis of the aggregate of signals flowing into the ... ...

Abstract	E2F1 is a transcription factor involved in both cell cycle progression and apoptosis. Perhaps surprisingly, these two processes are closely related, and the choice between them appears to be made on the basis of the aggregate of signals flowing into the cell at the time. This may be the means whereby normal cells tune their threshold for apoptosis with respect to the availability of external growth factors, so that cells that are supernumerary to the tissue's needs at the time can be immediately deleted. In many tumours, however, the pathways that link E2F1 activity to apoptosis have been interrupted, sometimes at multiple points. Non-small-cell lung carcinoma provides a striking example of this, with the result that expression of E2F1 in these tumours does not correlate with apoptosis but is a good surrogate marker for replicative status. This relationship does not necessarily pertain in other tumour types. Molecules such as E2F1 lie at the core of very significant cell fate decisions, but they are part of a complex matrix of interactions, all of which must be surveyed before interpretation in terms of tumour behaviour is possible. Microarray analysis may provide a way to do this. In the future, however, such interpretations, including predictions of therapeutic response, may be possible through interrogation of the status of a relatively limited number of molecules. Those that preside over critical cellular decision forks (such as the choice between proliferation or death) are good candidates for this role. E2F1 clearly qualifies as one member of this group.
MeSH term(s)	Apoptosis/genetics ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Cell Cycle/genetics ; Cell Cycle Proteins/physiology ; DNA-Binding Proteins ; E2F Transcription Factors ; E2F1 Transcription Factor ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Neoplasm Proteins/physiology ; Transcription Factors/physiology
Chemical Substances	Cell Cycle Proteins ; DNA-Binding Proteins ; E2F Transcription Factors ; E2F1 Transcription Factor ; E2F1 protein, human ; Neoplasm Proteins ; Transcription Factors
Language	English
Publishing date	2002-10
Publishing country	England
Document type	Comment ; Journal Article
ZDB-ID	3119-7
ISSN	1096-9896 ; 0022-3417
ISSN (online)	1096-9896
ISSN	0022-3417
DOI	10.1002/path.1238
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Article ; Online: Combining viral genomics and clinical data to assess risk factors for severe COVID-19 (mortality, ICU admission, or intubation) amongst hospital patients in a large acute UK NHS hospital Trust

PLoS ONE, Vol 18, Iss

2023 Volume 3

Abstract	Throughout the COVID-19 pandemic, valuable datasets have been collected on the effects of the virus SARS-CoV-2. In this study, we combined whole genome sequencing data with clinical data (including clinical outcomes, demographics, comorbidity, treatment information) for 929 patient cases seen at a large UK hospital Trust between March 2020 and May 2021. We identified associations between acute physiological status and three measures of disease severity; admission to the intensive care unit (ICU), requirement for intubation, and mortality. Whilst the maximum National Early Warning Score (NEWS2) was moderately associated with severe COVID-19 (A = 0.48), the admission NEWS2 was only weakly associated (A = 0.17), suggesting it is ineffective as an early predictor of severity. Patient outcome was weakly associated with myriad factors linked to acute physiological status and human genetics, including age, sex and pre-existing conditions. Overall, we found no significant links between viral genomics and severe outcomes, but saw evidence that variant subtype may impact relative risk for certain sub-populations. Specific mutations of SARS-CoV-2 appear to have little impact on overall severity risk in these data, suggesting that emerging SARS-CoV-2 variants do not result in more severe patient outcomes. However, our results show that determining a causal relationship between mutations and severe COVID-19 in the viral genome is challenging. Whilst improved understanding of the evolution of SARS-CoV-2 has been achieved through genomics, few studies on how these evolutionary changes impact on clinical outcomes have been seen due to complexities associated with data linkage. By combining viral genomics with patient records in a large acute UK hospital, this study represents a significant resource for understanding risk factors associated with COVID-19 severity. However, further understanding will likely arise from studies of the role of host genetics on disease progression.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: An adenoviral-vectored vaccine confers seroprotection against capsular group B meningococcal disease.

Dold, Christina / Marsay, Leanne / Wang, Nelson / Silva-Reyes, Laura / Clutterbuck, Elizabeth / Paterson, Gavin K / Sharkey, Kelsey / Wyllie, David / Beernink, Peter T / Hill, Adrian V / Pollard, Andrew J / Rollier, Christine S

Science translational medicine

2023 Volume 15, Issue 701, Page(s) eade3901

Abstract: ... MenB). Vector-based candidate vaccines expressing MenB antigen factor H binding protein (fHbp) were ... use by incorporating a mutation abrogating binding to the human complement inhibitor factor H ... factor H. The optimized transgene was inserted into the clinically relevant ChAdOx1 backbone, and ...

Abstract	Adenoviral-vectored vaccines are licensed for prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ebola virus, but, for bacterial proteins, expression in a eukaryotic cell may affect the antigen's localization and conformation or lead to unwanted glycosylation. Here, we investigated the potential use of an adenoviral-vectored vaccine platform for capsular group B meningococcus (MenB). Vector-based candidate vaccines expressing MenB antigen factor H binding protein (fHbp) were generated, and immunogenicity was assessed in mouse models, including the functional antibody response by serum bactericidal assay (SBA) using human complement. All adenovirus-based vaccine candidates induced high antigen-specific antibody and T cell responses. A single dose induced functional serum bactericidal responses with titers superior or equal to those induced by two doses of protein-based comparators, as well as longer persistence and a similar breadth. The fHbp transgene was further optimized for human use by incorporating a mutation abrogating binding to the human complement inhibitor factor H. The resulting vaccine candidate induced high and persistent SBA responses in transgenic mice expressing human factor H. The optimized transgene was inserted into the clinically relevant ChAdOx1 backbone, and this vaccine has now progressed to clinical development. The results of this preclinical vaccine development study underline the potential of vaccines based on genetic material to induce functional antibody responses against bacterial outer membrane proteins.
MeSH term(s)	Humans ; Mice ; Animals ; Complement Factor H ; Meningococcal Vaccines ; Neisseria meningitidis, Serogroup B ; COVID-19 ; SARS-CoV-2 ; Antigens, Bacterial ; Bacterial Proteins/genetics ; Meningococcal Infections/prevention & control ; Neisseria meningitidis ; Carrier Proteins ; Mice, Transgenic ; Viral Vaccines ; Adenoviridae/genetics ; Antibodies, Bacterial
Chemical Substances	Complement Factor H (80295-65-4) ; Meningococcal Vaccines ; Antigens, Bacterial ; Bacterial Proteins ; Carrier Proteins ; Viral Vaccines ; Antibodies, Bacterial
Language	English
Publishing date	2023-06-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.ade3901
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Article ; Online: Viral vectors expressing group B meningococcal outer membrane proteins induce strong antibody responses but fail to induce functional bactericidal activity.

Marsay, Leanne / Dold, Christina / Paterson, Gavin K / Yamaguchi, Yuko / Derrick, Jeremy P / Chan, Hannah / Feavers, Ian M / Maiden, Martin C J / Wyllie, David / Hill, Adrian V / Pollard, Andrew J / Rollier, Christine S

The Journal of infection

2022 Volume 84, Issue 5, Page(s) 658–667

Abstract: Objective: Adenoviral vectored vaccines, with the appropriate gene insert, induce cellular and antibody responses against viruses, parasites and intracellular pathogens such as Mycobacterium tuberculosis. Here we explored their capacity to induce ... ...

Abstract	Objective: Adenoviral vectored vaccines, with the appropriate gene insert, induce cellular and antibody responses against viruses, parasites and intracellular pathogens such as Mycobacterium tuberculosis. Here we explored their capacity to induce functional antibody responses to meningococcal transmembrane outer membrane proteins. Methods: Vectors expressing porin A and ferric enterobactin receptor A antigens were generated, and their immunogenicity assessed in mice using binding and bactericidal assays. Results: The viral vectors expressed the bacterial proteins in an in vitro cell-infection assay and, after immunisation of mice, induced higher titres (>10 Conclusion: These results demonstrate that, while the transmembrane bacterial proteins expressed by the viral vector induced strong and persistent antigen-specific antibodies, this platform failed to induce bactericidal antibodies. The results suggest that conformation or post-translational modifications of bacterial outer membrane antigens produced in eukaryote cells might not result in presentation of the necessary epitopes for induction of functional antibodies.
MeSH term(s)	Animals ; Antibodies, Bacterial ; Antibody Formation ; Antigens, Bacterial/genetics ; Bacterial Outer Membrane Proteins/genetics ; Bacterial Proteins ; Bacterial Vaccines ; Humans ; Meningococcal Vaccines ; Mice ; Neisseria meningitidis/genetics
Chemical Substances	Antibodies, Bacterial ; Antigens, Bacterial ; Bacterial Outer Membrane Proteins ; Bacterial Proteins ; Bacterial Vaccines ; Meningococcal Vaccines
Language	English
Publishing date	2022-03-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424417-5
ISSN	1532-2742 ; 0163-4453
ISSN (online)	1532-2742
ISSN	0163-4453
DOI	10.1016/j.jinf.2022.02.032
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