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Article ; Online: M. tuberculosis

Bernard, Elliott M / Fearns, Antony / Bussi, Claudio / Santucci, Pierre / Peddie, Christopher J / Lai, Rachel J / Collinson, Lucy M / Gutierrez, Maximiliano G

Journal of cell science

2020 Volume 134, Issue 5

Abstract: Xenophagy is an important cellular defence mechanism against cytosol-invading pathogens, such ... ...

Abstract	Xenophagy is an important cellular defence mechanism against cytosol-invading pathogens, such as
MeSH term(s)	Autophagy ; Humans ; Induced Pluripotent Stem Cells ; Macroautophagy ; Macrophages ; Mycobacterium tuberculosis ; Tuberculosis
Language	English
Publishing date	2020-11-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.252973
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Article ; Online: A terpene nucleoside from M. tuberculosis induces lysosomal lipid storage in foamy macrophages.

The Journal of clinical investigation

2023 Volume 133, Issue 6

Abstract: ... in M1 macrophages. Pure 1-TbAd, or infection with terpenyl nucleoside-producing M. tuberculosis, caused ... cholesterylesters and that 1-TbAd increased M. tuberculosis growth under conditions of restricted lipid access ... of M. tuberculosis-induced lysosomal failure, leading to successful testing of an agonist of TRPML1 ...

Abstract	Induction of lipid-laden foamy macrophages is a cellular hallmark of tuberculosis (TB) disease, which involves the transformation of infected phagolysosomes from a site of killing into a nutrient-rich replicative niche. Here, we show that a terpenyl nucleoside shed from Mycobacterium tuberculosis, 1-tuberculosinyladenosine (1-TbAd), caused lysosomal maturation arrest and autophagy blockade, leading to lipid storage in M1 macrophages. Pure 1-TbAd, or infection with terpenyl nucleoside-producing M. tuberculosis, caused intralysosomal and peribacillary lipid storage patterns that matched both the molecules and subcellular locations known in foamy macrophages. Lipidomics showed that 1-TbAd induced storage of triacylglycerides and cholesterylesters and that 1-TbAd increased M. tuberculosis growth under conditions of restricted lipid access in macrophages. Furthermore, lipidomics identified 1-TbAd-induced lipid substrates that define Gaucher's disease, Wolman's disease, and other inborn lysosomal storage diseases. These data identify genetic and molecular causes of M. tuberculosis-induced lysosomal failure, leading to successful testing of an agonist of TRPML1 calcium channels that reverses lipid storage in cells. These data establish the host-directed cellular functions of an orphan effector molecule that promotes survival in macrophages, providing both an upstream cause and detailed picture of lysosome failure in foamy macrophages.
MeSH term(s)	Humans ; Mycobacterium tuberculosis ; Terpenes ; Nucleosides ; Tuberculosis ; Macrophages/microbiology ; Lipids ; Lysosomes
Chemical Substances	Terpenes ; Nucleosides ; Lipids
Language	English
Publishing date	2023-03-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI161944
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Article ; Online: A terpene nucleoside from M. tuberculosis induces lysosomal lipid storage in foamy macrophages

The Journal of Clinical Investigation, Vol 133, Iss

2023 Volume 6

Abstract: ... in M1 macrophages. Pure 1-TbAd, or infection with terpenyl nucleoside–producing M. tuberculosis, caused ... cholesterylesters and that 1-TbAd increased M. tuberculosis growth under conditions of restricted lipid access ... of M. tuberculosis–induced lysosomal failure, leading to successful testing of an agonist of TRPML1 ...

Abstract	Induction of lipid-laden foamy macrophages is a cellular hallmark of tuberculosis (TB) disease, which involves the transformation of infected phagolysosomes from a site of killing into a nutrient-rich replicative niche. Here, we show that a terpenyl nucleoside shed from Mycobacterium tuberculosis, 1-tuberculosinyladenosine (1-TbAd), caused lysosomal maturation arrest and autophagy blockade, leading to lipid storage in M1 macrophages. Pure 1-TbAd, or infection with terpenyl nucleoside–producing M. tuberculosis, caused intralysosomal and peribacillary lipid storage patterns that matched both the molecules and subcellular locations known in foamy macrophages. Lipidomics showed that 1-TbAd induced storage of triacylglycerides and cholesterylesters and that 1-TbAd increased M. tuberculosis growth under conditions of restricted lipid access in macrophages. Furthermore, lipidomics identified 1-TbAd–induced lipid substrates that define Gaucher’s disease, Wolman’s disease, and other inborn lysosomal storage diseases. These data identify genetic and molecular causes of M. tuberculosis–induced lysosomal failure, leading to successful testing of an agonist of TRPML1 calcium channels that reverses lipid storage in cells. These data establish the host-directed cellular functions of an orphan effector molecule that promotes survival in macrophages, providing both an upstream cause and detailed picture of lysosome failure in foamy macrophages.
Keywords	Infectious disease ; Microbiology ; Medicine ; R
Subject code	572
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	American Society for Clinical Investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Diurnal Differences in Human Muscle Isometric Force In Vivo Are Associated with Differential Phosphorylation of Sarcomeric M-Band Proteins.

Ab Malik, Zulezwan / Bowden Davies, Kelly A / Hall, Elliott C R / Barrett, Jennifer / Pullinger, Samuel A / Erskine, Robert M / Shepherd, Sam O / Iqbal, Zafar / Edwards, Ben J / Burniston, Jatin G

Proteomes

2020 Volume 8, Issue 3

Abstract: We investigated whether diurnal differences in muscle force output are associated with the post-translational state of muscle proteins. Ten physically active men (mean ± SD; age 26.7 ± 3.7 y) performed experimental sessions in the morning (08:00 h) and ... ...

Abstract	We investigated whether diurnal differences in muscle force output are associated with the post-translational state of muscle proteins. Ten physically active men (mean ± SD; age 26.7 ± 3.7 y) performed experimental sessions in the morning (08:00 h) and evening (17:00 h), which were counterbalanced in order of administration and separated by at least 72 h. Knee extensor maximal voluntary isometric contraction (MVIC) force and peak rate of force development (RFD) were measured, and samples of vastus lateralis were collected immediately after exercise. MVIC force was greater in the evening (mean difference of 67 N, 10.2%;
Language	English
Publishing date	2020-08-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720995-7
ISSN	2227-7382
ISSN	2227-7382
DOI	10.3390/proteomes8030022
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Article ; Online: M Segment-Based Minigenomes and Virus-Like Particle Assays as an Approach To Assess the Potential of Tick-Borne

Rezelj, Veronica V / Mottram, Timothy J / Hughes, Joseph / Elliott, Richard M / Kohl, Alain / Brennan, Benjamin

Journal of virology

2019 Volume 93, Issue 6

Abstract: ... of viral N and L proteins to recognize, transcribe, and replicate the M segment-based minigenome ... of a heterologous virus. The highest minigenome activity was detected with the M segment-based minigenomes ... of heterologous viruses resulted in M segment minigenome activity. This suggests that the M segment ...

Abstract	Bunyaviruses have a tripartite negative-sense RNA genome. Due to the segmented nature of these viruses, if two closely related viruses coinfect the same host or vector cell, it is possible that RNA segments from either of the two parental viruses will be incorporated into progeny virions to give reassortant viruses. Little is known about the ability of tick-borne phleboviruses to reassort. The present study describes the development of minigenome assays for the tick-borne viruses Uukuniemi phlebovirus (UUKV) and Heartland phlebovirus (HRTV). We used these minigenome assays in conjunction with the existing minigenome system of severe fever with thrombocytopenia syndrome (SFTS) phlebovirus (SFTSV) to assess the abilities of viral N and L proteins to recognize, transcribe, and replicate the M segment-based minigenome of a heterologous virus. The highest minigenome activity was detected with the M segment-based minigenomes of cognate viruses. However, our findings indicate that several combinations utilizing N and L proteins of heterologous viruses resulted in M segment minigenome activity. This suggests that the M segment untranslated regions (UTRs) are recognized as functional promoters of transcription and replication by the N and L proteins of related viruses. Further, virus-like particle assays demonstrated that HRTV glycoproteins can package UUKV and SFTSV S and L segment-based minigenomes. Taken together, these results suggest that coinfection with these viruses could lead to the generation of viable reassortant progeny. Thus, the tools developed in this study could aid in understanding the role of genome reassortment in the evolution of these emerging pathogens in an experimental setting.
MeSH term(s)	Animals ; Bunyaviridae Infections/virology ; Cell Line ; Genome, Viral/genetics ; Mesocricetus ; Phlebovirus/genetics ; Phylogeny ; Promoter Regions, Genetic/genetics ; Ticks/virology ; Viral Nonstructural Proteins/genetics
Chemical Substances	Viral Nonstructural Proteins
Language	English
Publishing date	2019-03-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.02068-18
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Article: Tuning the Catalytic Water Oxidation Activity through Structural Modifications of High-Nuclearity Mn-oxo Clusters [Mn18M] (M = Sr2+, Mn2+)

Soriano-López, Joaquín / Elliott, Rory / Kathalikkattil, Amal C. / Ako, Ayuk M. / Schmitt, Wolfgang

Water. 2021 July 27, v. 13, no. 15

2021

Abstract: The water oxidation half-reaction is considered the bottleneck in the development of technological advances to replace fossil fuels with sustainable and economically affordable energy sources. In natural photosynthesis, water oxidation occurs in the ... ...

Abstract	The water oxidation half-reaction is considered the bottleneck in the development of technological advances to replace fossil fuels with sustainable and economically affordable energy sources. In natural photosynthesis, water oxidation occurs in the oxygen evolving complex (OEC), a manganese-oxo cluster {Mn₄CaO₅} with a cubane-like topology that is embedded within a redox-active protein environment located in photosystem II (PS II). Therefore, the preparation of biomimetic manganese-based compounds is appealing for the development of efficient and inexpensive water oxidation catalysts. Here, we present the water oxidation catalytic activity of a high-nuclearity mixed-metal manganese-strontium cluster, [Mnᴵᴵᴵ₁₂Mnᴵᴵ₆Sr(μ₄-O₈)(μ₃-Cl)₈(HLᴹᵉ)₁₂(MeCN)₆]Cl₂∙15MeOH (Mn₁₈Sr) (HLᴹᵉ = 2,6-bis(hydroxymethyl)-p-cresol), in neutral media. This biomimetic mixed-valence cluster features different cubane-like motifs and it is stabilized by redox-active, quinone-like organic ligands. The complex displays a low onset overpotential of 192 mV and overpotentials of 284 and 550 mV at current densities of 1 mA cm⁻² and 10 mA cm⁻², respectively. Direct O₂ evolution measurements under visible light-driven water oxidation conditions demonstrate the catalytic capabilities of this cluster, which exhibits a turnover frequency of 0.48 s⁻¹ and a turnover number of 21.6. This result allows for a direct comparison to be made with the structurally analogous Mn-oxo cluster [Mnᴵᴵᴵ₁₂Mnᴵᴵ₇(µ₄-O)₈(µ₃-OCH₃)₂(µ₃-Br)₆(HLᴹᵉ)₁₂(MeOH)₅(MeCN)]Br₂·9MeCN·MeOH (Mn₁₉), the water oxidation catalytic activity of which was recently reported by us. This work highlights the potential of this series of compounds towards the water oxidation reaction and their amenability to induce structural changes that modify their reactivity.
Keywords	biomimetics ; catalytic activity ; energy ; ligands ; oxidation ; oxygen ; topology ; water
Language	English
Dates of publication	2021-0727
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2521238-2
ISSN	2073-4441
ISSN	2073-4441
DOI	10.3390/w13152042
Database	NAL-Catalogue (AGRICOLA)

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Article: The Skraup reaction with m-substituted anilines.

BRADFORD, L / ELLIOTT, T J / ROWE, F M

Journal of the Chemical Society

2010 , Page(s) 437–445

MeSH term(s)	Aniline Compounds ; Humans
Chemical Substances	Aniline Compounds ; aniline (SIR7XX2F1K)
Language	English
Publishing date	2010-02-04
Publishing country	England
Document type	Journal Article
ZDB-ID	215831-0
ISSN	0368-1769 ; 0368-1645 ; 0300-9246 ; 0590-9791
ISSN	0368-1769 ; 0368-1645 ; 0300-9246 ; 0590-9791
DOI	10.1039/jr9470000437
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Article ; Online: Type 2 diabetes with BMI<30 kg/m

Elliott, Jessie A / le Roux, Carel W

Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery

2016 Volume 12, Issue 7, Page(s) 1363–1365

MeSH term(s)	Bariatric Surgery ; Body Mass Index ; Diabetes Mellitus, Type 2 ; Glycated Hemoglobin A ; Humans ; Obesity, Morbid
Chemical Substances	Glycated Hemoglobin A
Language	English
Publishing date	2016
Publishing country	United States
Document type	Editorial
ZDB-ID	2274243-8
ISSN	1878-7533 ; 1550-7289
ISSN (online)	1878-7533
ISSN	1550-7289
DOI	10.1016/j.soard.2016.03.012
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Article ; Online: Functional DNA methylation differences between tissues, cell types, and across individuals discovered using the M&M algorithm.

Zhang, Bo / Zhou, Yan / Lin, Nan / Lowdon, Rebecca F / Hong, Chibo / Nagarajan, Raman P / Cheng, Jeffrey B / Li, Daofeng / Stevens, Michael / Lee, Hyung Joo / Xing, Xiaoyun / Zhou, Jia / Sundaram, Vasavi / Elliott, Ginell / Gu, Junchen / Shi, Taoping / Gascard, Philippe / Sigaroudinia, Mahvash / Tlsty, Thea D /

Kadlecek, Theresa / Weiss, Arthur / O'Geen, Henriette / Farnham, Peggy J / Maire, Cécile L / Ligon, Keith L / Madden, Pamela A F / Tam, Angela / Moore, Richard / Hirst, Martin / Marra, Marco A / Zhang, Baoxue / Costello, Joseph F / Wang, Ting

Genome research

2013 Volume 23, Issue 9, Page(s) 1522–1540

Abstract: ... a novel integrative statistical framework M&M (for integration of MeDIP-seq and MRE-seq) that dynamically ... superior accuracy and reproducibility of M&M compared to existing analytical methods for MeDIP-seq data ... alone. M&M leverages the complementary nature of MeDIP-seq and MRE-seq data to allow rapid comparative ...

Abstract	DNA methylation plays key roles in diverse biological processes such as X chromosome inactivation, transposable element repression, genomic imprinting, and tissue-specific gene expression. Sequencing-based DNA methylation profiling provides an unprecedented opportunity to map and compare complete DNA methylomes. This includes one of the most widely applied technologies for measuring DNA methylation: methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq), coupled with a complementary method, methylation-sensitive restriction enzyme sequencing (MRE-seq). A computational approach that integrates data from these two different but complementary assays and predicts methylation differences between samples has been unavailable. Here, we present a novel integrative statistical framework M&M (for integration of MeDIP-seq and MRE-seq) that dynamically scales, normalizes, and combines MeDIP-seq and MRE-seq data to detect differentially methylated regions. Using sample-matched whole-genome bisulfite sequencing (WGBS) as a gold standard, we demonstrate superior accuracy and reproducibility of M&M compared to existing analytical methods for MeDIP-seq data alone. M&M leverages the complementary nature of MeDIP-seq and MRE-seq data to allow rapid comparative analysis between whole methylomes at a fraction of the cost of WGBS. Comprehensive analysis of nineteen human DNA methylomes with M&M reveals distinct DNA methylation patterns among different tissue types, cell types, and individuals, potentially underscoring divergent epigenetic regulation at different scales of phenotypic diversity. We find that differential DNA methylation at enhancer elements, with concurrent changes in histone modifications and transcription factor binding, is common at the cell, tissue, and individual levels, whereas promoter methylation is more prominent in reinforcing fundamental tissue identities.
MeSH term(s)	Algorithms ; DNA Methylation ; Data Interpretation, Statistical ; Genome, Human ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Organ Specificity ; Sequence Analysis, DNA/methods
Language	English
Publishing date	2013-06-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.156539.113
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Article ; Online: "And DPSIR begat DAPSI(W)R(M)!" - A unifying framework for marine environmental management.

Elliott, M / Burdon, D / Atkins, J P / Borja, A / Cormier, R / de Jonge, V N / Turner, R K

Marine pollution bulletin

2017 Volume 118, Issue 1-2, Page(s) 27–40

Abstract: ... advocates that DPSIR should be extended to DAPSI(W)R(M) (pronounced dap-see-worm) in which Drivers of basic ... the need for a linked-DAPSI(W)R(M) framework, and then the connectivity between marine ecosystems and ... ecosystems in the catchment and further at sea, requires an interlinked, nested-DAPSI(W)R(M) framework ...

Abstract	The marine environment is a complex system formed by interactions between ecological structure and functioning, physico-chemical processes and socio-economic systems. An increase in competing marine uses and users requires a holistic approach to marine management which considers the environmental, economic and societal impacts of all activities. If managed sustainably, the marine environment will deliver a range of ecosystem services which lead to benefits for society. In order to understand the complexity of the system, the DPSIR (Driver-Pressure-State-Impact-Response) approach has long been a valuable problem-structuring framework used to assess the causes, consequences and responses to change in a holistic way. Despite DPSIR being used for a long time, there is still confusion over the definition of its terms and so to be appropriate for current marine management, we contend that this confusion needs to be addressed. Our viewpoint advocates that DPSIR should be extended to DAPSI(W)R(M) (pronounced dap-see-worm) in which Drivers of basic human needs require Activities which lead to Pressures. The Pressures are the mechanisms of State change on the natural system which then leads to Impacts (on human Welfare). Those then require Responses (as Measures). Furthermore, because of the complexity of any managed sea area in terms of multiple Activities, there is the need for a linked-DAPSI(W)R(M) framework, and then the connectivity between marine ecosystems and ecosystems in the catchment and further at sea, requires an interlinked, nested-DAPSI(W)R(M) framework to reflect the continuum between adjacent ecosystems. Finally, the unifying framework for integrated marine management is completed by encompassing ecosystem structure and functioning, ecosystem services and societal benefits. Hence, DAPSI(W)R(M) links the socio-ecological system of the effects of changes to the natural system on the human uses and benefits of the marine system. However, to deliver these sustainably in the light of human activities requires a Risk Assessment and Risk Management framework; the ISO-compliant Bow-Tie method is used here as an example. Finally, to secure ecosystem health and economic benefits such as Blue Growth, successful, adaptive and sustainable marine management Responses (as Measures) are delivered using the 10-tenets, a set of facets covering all management disciplines and approaches.
MeSH term(s)	Conservation of Natural Resources/methods ; Ecology ; Ecosystem ; Human Activities ; Humans ; Oceans and Seas ; Risk Assessment ; Risk Management
Language	English
Publishing date	2017-05-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2001296-2
ISSN	1879-3363 ; 0025-326X
ISSN (online)	1879-3363
ISSN	0025-326X
DOI	10.1016/j.marpolbul.2017.03.049
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