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Article ; Online: Autophagy as a defence against intracellular pathogens.

Wileman, Tom

2013 Volume 55, Page(s) 153–163

Abstract: Autophagy is a membrane trafficking pathway that results in the formation of autophagosomes which deliver portions of the cytosol to lysosomes for degradation. When autophagosomes engulf intracellular pathogens, the pathway is called 'xenophagy' because ... ...

Abstract	Autophagy is a membrane trafficking pathway that results in the formation of autophagosomes which deliver portions of the cytosol to lysosomes for degradation. When autophagosomes engulf intracellular pathogens, the pathway is called 'xenophagy' because it leads to the removal of foreign material. Autophagy is activated during infection by Toll-like receptors that recognize pathogen-associated molecular patterns. This allows autophagy to kill micro-organisms and present pathogen components to the innate and acquired immune systems. The targeting of pathogens by autophagy is selective and involves a growing family of autophagy receptors that bind to the autophagosome membrane protein LC3 (light-chain 3)/Atg8 (autography-related protein 8). Ubiquitination of microbes identifies them as substrates for autophagy and they are delivered to autophagosomes by autophagy receptors that bind both ubiquitin and LC3/Atg8. Bacteria can also be detected before they enter the cytosol by autophagy receptors that scan the surface of membrane compartments for evidence of damage. The observation that some pathogens survive in cells suggests they can evade complete destruction by autophagy. For some bacteria this involves proteins that shield the surface of the bacteria from recognition by autophagy receptors. Other viruses and bacteria are resistant to degradation in lysosomes and use autophagosomes and/or lysosomes as sites for replication. Most of our current understanding of the role played by autophagy during microbial infection has come from studies of bacteria and viruses in tissue culture cell lines. Future work will focus on understanding how autophagy determines the outcome of infection 'in vivo', and how autophagy pathways can be exploited therapeutically.
MeSH term(s)	Animals ; Autophagy ; Bacteria/pathogenicity ; Host-Pathogen Interactions ; Humans ; Lysosomes/metabolism ; Lysosomes/microbiology ; Lysosomes/virology ; Phagosomes/metabolism ; Phagosomes/microbiology ; Phagosomes/virology ; Viruses/pathogenicity
Language	English
Publishing date	2013-09-26
Publishing country	England
Document type	Journal Article ; Review
ISSN	1744-1358 ; 0071-1365
ISSN (online)	1744-1358
ISSN	0071-1365
DOI	10.1042/bse0550153
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Autophagy Driven Extracellular Vesicles in the Leukaemic Microenvironment.

Horton, Rebecca H / Wileman, Tom / Rushworth, Stuart A

Current cancer drug targets

2020 Volume 20, Issue 7, Page(s) 501–512

Abstract: The leukaemias are a heterogeneous group of blood cancers, which together, caused 310,000 deaths in 2016. Despite significant research into their biology and therapeutics, leukaemia is predicted to account for an increased 470,000 deaths in 2040. Many ... ...

Abstract	The leukaemias are a heterogeneous group of blood cancers, which together, caused 310,000 deaths in 2016. Despite significant research into their biology and therapeutics, leukaemia is predicted to account for an increased 470,000 deaths in 2040. Many subtypes remain without targeted therapy, and therefore the mainstay of treatment remains generic cytotoxic drugs with bone marrow transplant the sole definitive option. In this review, we will focus on cellular mechanisms which have the potential for therapeutic exploitation to specifically target and treat this devastating disease. We will bring together the disciplines of autophagy and extracellular vesicles, exploring how the dysregulation of these mechanisms can lead to changes in the leukaemic microenvironment and the subsequent propagation of disease. The dual effect of these mechanisms in the disease microenvironment is not limited to leukaemia; therefore, we briefly explore their role in autoimmunity, inflammation and degenerative disease.
MeSH term(s)	Animals ; Autoimmunity ; Autophagy ; Extracellular Vesicles/metabolism ; Humans ; Inflammation/metabolism ; Leukemia, Myeloid, Acute/immunology ; Leukemia, Myeloid, Acute/metabolism ; Signal Transduction ; Tumor Microenvironment
Language	English
Publishing date	2020-03-30
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2064824-8
ISSN	1873-5576 ; 1568-0096
ISSN (online)	1873-5576
ISSN	1568-0096
DOI	10.2174/1568009620666200428111051
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Exploring Endotypes in Chronic Rhinosinusitis (ExpRess): Protocol for a cohort study.

Gokani, Shyam Ajay / Jefferson, Matthew / Gavrilovic, Jelena / Clark, Allan / Hildebrand, Falk / Wileman, Tom / Hopkins, Claire / Philpott, Carl

PloS one

2023 Volume 18, Issue 8, Page(s) e0289407

Abstract: Background: Chronic Rhinosinusitis (CRS) affects approximately 1 in 10 UK adults and impacts quality of life quality of life significantly. Response to treatment may be driven by individual CRS endotypes and therefore work to delineate biomarker ... ...

Abstract	Background: Chronic Rhinosinusitis (CRS) affects approximately 1 in 10 UK adults and impacts quality of life quality of life significantly. Response to treatment may be driven by individual CRS endotypes and therefore work to delineate biomarker clusters that may separate responders from non-responders is needed. The ongoing MACRO three-arm parallel-group trial randomises adult CRS patients to endoscopic sinus surgery, macrolide therapy or placebo. Aim: This study aims to correlate CRS endotypes with clinical parameters from the ongoing MACRO trial, including olfactory function and outcomes in terms of response to treatment using core biomarkers sets. Methods: Adult CRS patients enrolled into the MACRO trial will be recruited from participating UK otorhinolaryngology departments. Nasal tissue samples and swabs will be obtained in theatre or clinic from patients randomised to all three trial arms. Nasal tissue will be analysed with multiplex electrochemiluminescence for 32 cytokines including IL-5, IL-13, IgE and periostin. Bacterial swabs will be analysed using illumina miSeq 16S amplicon sequencing. Mean expression for each biomarker will be reported for treatment responder and non-responder groups. Correlation of biomarkers with MACRO trial outcome data such as endoscopic evaluation scores and quality-of-life improvement scores will be reported. Discussion: Defining clear endotypes in CRS will contribute to refining patient pathways for the efficient use of clinical resources. This work may lay the groundwork for future studies to predict which patients might respond to medical or surgical therapy.
MeSH term(s)	Adult ; Humans ; Rhinitis ; Cohort Studies ; Quality of Life ; Sinusitis ; Biomarkers/analysis ; Nasal Polyps/metabolism ; Chronic Disease ; Randomized Controlled Trials as Topic
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-08-02
Publishing country	United States
Document type	Clinical Trial Protocol ; 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.0289407
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Article ; Online: Lifespan extension without fertility reduction following dietary addition of the autophagy activator Torin1 in Drosophila melanogaster.

Mason, Janet S / Wileman, Tom / Chapman, Tracey

PloS one

2018 Volume 13, Issue 1, Page(s) e0190105

Abstract: Autophagy is a highly conserved mechanism for cellular repair that becomes progressively down-regulated during normal ageing. Hence, manipulations that activate autophagy could increase lifespan. Previous reports show that manipulations to the autophagy ... ...

Abstract	Autophagy is a highly conserved mechanism for cellular repair that becomes progressively down-regulated during normal ageing. Hence, manipulations that activate autophagy could increase lifespan. Previous reports show that manipulations to the autophagy pathway can result in longevity extension in yeast, flies, worms and mammals. Under standard nutrition, autophagy is inhibited by the nutrient sensing kinase Target of Rapamycin (TOR). Therefore, manipulations of TOR that increase autophagy may offer a mechanism for extending lifespan. Ideally, such manipulations should be specific and minimise off-target effects, and it is important to discover additional methods for 'clean' lifespan manipulation. Here we report an initial study into the effect of up-regulating autophagy on lifespan and fertility in Drosophila melanogaster by dietary addition of Torin1. Activation of autophagy using this selective TOR inhibitor was associated with significantly increased lifespan in both sexes. Torin1 induced a dose-dependent increase in lifespan in once-mated females. There was no evidence of a trade-off between longevity and fecundity or fertility. Torin1-fed females exhibited significantly elevated fecundity, but also elevated egg infertility, resulting in no net change in overall fertility. This supports the idea that lifespan can be extended without trade-offs in fertility and suggest that Torin1 may be a useful tool with which to pursue anti-ageing research.
MeSH term(s)	Animals ; Autophagy ; Drosophila melanogaster/physiology ; Female ; Fertility ; Male ; Naphthyridines/administration & dosage
Chemical Substances	1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one ; Naphthyridines
Language	English
Publishing date	2018-01-12
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.0190105
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Article ; Online: Autophagy, Acute Pancreatitis and the Metamorphoses of a Trypsinogen-Activating Organelle.

Voronina, Svetlana / Chvanov, Michael / De Faveri, Francesca / Mayer, Ulrike / Wileman, Tom / Criddle, David / Tepikin, Alexei

Cells

2022 Volume 11, Issue 16

Abstract: Recent studies have highlighted the importance of autophagy and particularly non-canonical autophagy in the development and progression of acute pancreatitis (a frequent disease with considerable morbidity and significant mortality). An important early ... ...

Abstract	Recent studies have highlighted the importance of autophagy and particularly non-canonical autophagy in the development and progression of acute pancreatitis (a frequent disease with considerable morbidity and significant mortality). An important early event in the development of acute pancreatitis is the intrapancreatic activation of trypsinogen, (i.e., formation of trypsin) leading to the autodigestion of the organ. Another prominent phenomenon associated with the initiation of this disease is vacuolisation and specifically the formation of giant endocytic vacuoles in pancreatic acinar cells. These organelles develop in acinar cells exposed to several inducers of acute pancreatitis (including taurolithocholic acid and high concentrations of secretagogues cholecystokinin and acetylcholine). Notably, early trypsinogen activation occurs in the endocytic vacuoles. These trypsinogen-activating organelles undergo activation, long-distance trafficking, and non-canonical autophagy. In this review, we will discuss the role of autophagy in acute pancreatitis and particularly focus on the recently discovered LAP-like non-canonical autophagy (LNCA) of endocytic vacuoles.
MeSH term(s)	Acute Disease ; Autophagy ; Humans ; Pancreatitis ; Trypsinogen ; Vacuoles
Chemical Substances	Trypsinogen (9002-08-8)
Language	English
Publishing date	2022-08-12
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11162514
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Article ; Online: Systematic Review of Protein Biomarkers in Adult Patients With Chronic Rhinosinusitis.

Gokani, Shyam A / Espehana, Andreas / Pratas, Ana C / Luke, Louis / Sharma, Ekta / Mattock, Jennifer / Gavrilovic, Jelena / Clark, Allan / Wileman, Tom / Philpott, Carl M

American journal of rhinology & allergy

2023 Volume 37, Issue 6, Page(s) 705–729

Abstract: Background: Chronic rhinosinusitis (CRS) is a heterogeneous condition characterized by differing inflammatory endotypes. The identification of suitable biomarkers could enable personalized approaches to treatment selection.: Objective: This study ... ...

Abstract	Background: Chronic rhinosinusitis (CRS) is a heterogeneous condition characterized by differing inflammatory endotypes. The identification of suitable biomarkers could enable personalized approaches to treatment selection. Objective: This study aimed to identify and summarize clinical studies of biomarkers in adults with CRS in order to inform future research into CRS endotypes. Methods: We conducted systematic searches of MEDLINE and Web of Science from inception to January 30, 2022 and included all clinical studies of adult CRS patients and healthy controls measuring biomarkers using enzyme-linked immunosorbent assays or Luminex immunoassays. Outcomes included the name and tissue type of identified biomarkers and expression patterns within CRS phenotypes. Study quality was assessed using the National Institutes of Health quality assessment tool for observational cohort and cross-sectional studies. A narrative synthesis was performed. Results: We identified 78 relevant studies involving up to 9394 patients, predominantly with CRS with nasal polyposis. Studies identified 80 biomarkers from nasal tissue, 25 from nasal secretions, 14 from nasal lavage fluid, 24 from serum, and one from urine. The majority of biomarkers found to distinguish CRS phenotypes were identified in nasal tissue, especially in nasal polyps. Serum biomarkers were more commonly found to differentiate CRS from controls. The most frequently measured biomarker was IL-5, followed by IL-13 and IL-4. Serum IgE, IL-17, pentraxin-3 and nasal phospho-janus kinase 2, IL-5, IL-6, IL-17A, granulocyte-colony stimulating factor, and interferon gamma were identified as correlated with disease severity. Conclusion: We have identified numerous potential biomarkers to differentiate a range of CRS phenotypes. Future studies should focus on the prognostic role of nasal tissue biomarkers or expand on the more limited studies of nasal secretions and nasal lavage fluid.We registered this study in PROSPERO (CRD42022302787).
MeSH term(s)	Humans ; Adult ; Rhinitis/diagnosis ; Rhinitis/metabolism ; Interleukin-5/metabolism ; Cross-Sectional Studies ; Sinusitis/diagnosis ; Sinusitis/metabolism ; Biomarkers ; Nasal Polyps ; Chronic Disease
Chemical Substances	Interleukin-5 ; Biomarkers
Language	English
Publishing date	2023-07-25
Publishing country	United States
Document type	Systematic Review ; Journal Article
ZDB-ID	2482804-X
ISSN	1945-8932 ; 1945-8924
ISSN (online)	1945-8932
ISSN	1945-8924
DOI	10.1177/19458924231190568
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 2542: Show issues

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bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome?

Newberry, Fiona / Hsieh, Shen-Yuan / Wileman, Tom / Carding, Simon R

Clinical science (London, England : 1979)

2018 Volume 132, Issue 5, Page(s) 523–542

Abstract: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease of unknown aetiology. It is a heterogeneous disease characterized by various inflammatory, immune, viral, neurological and endocrine symptoms. ... ...

Abstract	Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) (ME/CFS) is a disabling and debilitating disease of unknown aetiology. It is a heterogeneous disease characterized by various inflammatory, immune, viral, neurological and endocrine symptoms. Several microbiome studies have described alterations in the bacterial component of the microbiome (dysbiosis) consistent with a possible role in disease development. However, in focusing on the bacterial components of the microbiome, these studies have neglected the viral constituent known as the virome. Viruses, particularly those infecting bacteria (bacteriophages), have the potential to alter the function and structure of the microbiome via gene transfer and host lysis. Viral-induced microbiome changes can directly and indirectly influence host health and disease. The contribution of viruses towards disease pathogenesis is therefore an important area for research in ME/CFS. Recent advancements in sequencing technology and bioinformatics now allow more comprehensive and inclusive investigations of human microbiomes. However, as the number of microbiome studies increases, the need for greater consistency in study design and analysis also increases. Comparisons between different ME/CFS microbiome studies are difficult because of differences in patient selection and diagnosis criteria, sample processing, genome sequencing and downstream bioinformatics analysis. It is therefore important that microbiome studies adopt robust, reproducible and consistent study design to enable more reliable and valid comparisons and conclusions to be made between studies. This article provides a comprehensive review of the current evidence supporting microbiome alterations in ME/CFS patients. Additionally, the pitfalls and challenges associated with microbiome studies are discussed.
MeSH term(s)	Bacteria/growth & development ; Bacteria/virology ; Bacteriophages/physiology ; Dysbiosis/microbiology ; Dysbiosis/physiopathology ; Dysbiosis/virology ; Fatigue Syndrome, Chronic/microbiology ; Fatigue Syndrome, Chronic/physiopathology ; Fatigue Syndrome, Chronic/virology ; Gastrointestinal Microbiome/physiology ; Host Microbial Interactions ; Humans ; Inflammation/microbiology ; Inflammation/physiopathology ; Inflammation/virology ; Models, Biological
Language	English
Publishing date	2018-03-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	206835-7
ISSN	1470-8736 ; 0301-0538 ; 0009-0360 ; 0143-5221
ISSN (online)	1470-8736
ISSN	0301-0538 ; 0009-0360 ; 0143-5221
DOI	10.1042/CS20171330
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Article: Comparison of PCR versus PCR-Free DNA Library Preparation for Characterising the Human Faecal Virome

Hsieh, Shen-Yuan / Tariq, Mohammad A. / Telatin, Andrea / Ansorge, Rebecca / Adriaenssens, Evelien M. / Savva, George M. / Booth, Catherine / Wileman, Tom / Hoyles, Lesley / Carding, Simon R.

Viruses. 2021 Oct. 18, v. 13, no. 10

2021

Abstract: The human intestinal microbiota is abundant in viruses, comprising mainly bacteriophages, occasionally outnumbering bacteria 10:1 and is termed the virome. Due to their high genetic diversity and the lack of suitable tools and reference databases, the ... ...

Abstract	The human intestinal microbiota is abundant in viruses, comprising mainly bacteriophages, occasionally outnumbering bacteria 10:1 and is termed the virome. Due to their high genetic diversity and the lack of suitable tools and reference databases, the virome remains poorly characterised and is often referred to as “viral dark matter”. However, the choice of sequencing platforms, read lengths and library preparation make study design challenging with respect to the virome. Here we have compared the use of PCR and PCR-free methods for sequence-library construction on the Illumina sequencing platform for characterising the human faecal virome. Viral DNA was extracted from faecal samples of three healthy donors and sequenced. Our analysis shows that most variation was reflecting the individually specific faecal virome. However, we observed differences between PCR and PCR-free library preparation that affected the recovery of low-abundance viral genomes. Using three faecal samples in this study, the PCR library preparation samples led to a loss of lower-abundance vOTUs evident in their PCR-free pairs (vOTUs 128, 6202 and 8364) and decreased the alpha-diversity indices (Chao1 p-value = 0.045 and Simpson p-value = 0.044). Thus, differences between PCR and PCR-free methods are important to consider when investigating “rare” members of the gut virome, with these biases likely negligible when investigating moderately and highly abundant viruses.
Keywords	DNA ; DNA libraries ; digestive system ; experimental design ; genetic variation ; humans ; intestinal microorganisms ; species diversity ; viral genome
Language	English
Dates of publication	2021-1018
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13102093
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Virus factories, double membrane vesicles and viroplasm generated in animal cells.

Netherton, Christopher L / Wileman, Tom

Current opinion in virology

2011 Volume 1, Issue 5, Page(s) 381–387

Abstract: Many viruses reorganise cellular membrane compartments and the cytoskeleton to generate subcellular microenvironments called virus factories or 'viroplasm'. These create a platform to concentrate replicase proteins, virus genomes and host proteins ... ...

Abstract	Many viruses reorganise cellular membrane compartments and the cytoskeleton to generate subcellular microenvironments called virus factories or 'viroplasm'. These create a platform to concentrate replicase proteins, virus genomes and host proteins required for replication and also protect against antiviral defences. There is growing interest in understanding how viruses induce such large changes in cellular organisation, and recent studies are beginning to reveal the relationship between virus factories and viroplasm and the cellular structures that house them. In this review, we discuss how three supergroups of (+)RNA viruses generate replication sites from membrane-bound organelles and highlight research on perinuclear factories induced by the nucleocytoplasmic large DNA viruses.
MeSH term(s)	Animals ; Cytoplasmic Vesicles/virology ; DNA Viruses/genetics ; DNA Viruses/physiology ; Humans ; Intracellular Membranes/virology ; RNA Viruses/genetics ; RNA Viruses/physiology ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Virus Diseases/virology ; Virus Replication
Chemical Substances	Viral Proteins
Keywords	covid19
Language	English
Publishing date	2011-10-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2611378-8
ISSN	1879-6265 ; 1879-6257
ISSN (online)	1879-6265
ISSN	1879-6257
DOI	10.1016/j.coviro.2011.09.008
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Article: Genome Characterization of a Novel Wastewater

Tariq, Mohammad A / Newberry, Fiona / Haagmans, Rik / Booth, Catherine / Wileman, Tom / Hoyles, Lesley / Clokie, Martha R J / Ebdon, James / Carding, Simon R

Frontiers in microbiology

2020 Volume 11, Page(s) 583378

Abstract: ... ...

Abstract	Bacteroides
Language	English
Publishing date	2020-10-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2020.583378
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