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Article ; Online: Bacterial Sigma Factors and Anti-Sigma Factors: Structure, Function and Distribution.

Paget, Mark S

2015 Volume 5, Issue 3, Page(s) 1245–1265

Abstract: Sigma factors are multi-domain subunits of bacterial RNA polymerase (RNAP) that play critical roles in transcription initiation, including the recognition and opening of promoters as well as the initial steps in RNA synthesis. This review focuses on the ... ...

Abstract	Sigma factors are multi-domain subunits of bacterial RNA polymerase (RNAP) that play critical roles in transcription initiation, including the recognition and opening of promoters as well as the initial steps in RNA synthesis. This review focuses on the structure and function of the major sigma-70 class that includes the housekeeping sigma factor (Group 1) that directs the bulk of transcription during active growth, and structurally-related alternative sigma factors (Groups 2-4) that control a wide variety of adaptive responses such as morphological development and the management of stress. A recurring theme in sigma factor control is their sequestration by anti-sigma factors that occlude their RNAP-binding determinants. Sigma factors are then released through a wide variety of mechanisms, often involving branched signal transduction pathways that allow the integration of distinct signals. Three major strategies for sigma release are discussed: regulated proteolysis, partner-switching, and direct sensing by the anti-sigma factor.
MeSH term(s)	Bacterial Proteins/antagonists & inhibitors ; Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Protein Transport ; Sigma Factor/antagonists & inhibitors ; Sigma Factor/chemistry ; Sigma Factor/metabolism
Chemical Substances	Bacterial Proteins ; Sigma Factor
Language	English
Publishing date	2015-06-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom5031245
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Article ; Online: Bacterial Sigma Factors and Anti-Sigma Factors

Mark S. Paget

Biomolecules, Vol 5, Iss 3, Pp 1245-

Structure, Function and Distribution

2015 Volume 1265

Abstract	Sigma factors are multi-domain subunits of bacterial RNA polymerase (RNAP) that play critical roles in transcription initiation, including the recognition and opening of promoters as well as the initial steps in RNA synthesis. This review focuses on the structure and function of the major sigma-70 class that includes the housekeeping sigma factor (Group 1) that directs the bulk of transcription during active growth, and structurally-related alternative sigma factors (Groups 2–4) that control a wide variety of adaptive responses such as morphological development and the management of stress. A recurring theme in sigma factor control is their sequestration by anti-sigma factors that occlude their RNAP-binding determinants. Sigma factors are then released through a wide variety of mechanisms, often involving branched signal transduction pathways that allow the integration of distinct signals. Three major strategies for sigma release are discussed: regulated proteolysis, partner-switching, and direct sensing by the anti-sigma factor.
Keywords	RNA polymerase ; transcription ; anti-sigma ; sigma ; partner-switching ; RIP ; signal transduction ; stress ; extracytoplasmic ; Biology (General) ; QH301-705.5 ; Science ; Q
Subject code	670
Language	English
Publishing date	2015-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Genomics-Enabled Management of Genetic Resources in Radiata Pine

Jaroslav Klápště / Ahmed Ismael / Mark Paget / Natalie J. Graham / Grahame T. Stovold / Heidi S. Dungey / Gancho T. Slavov

Forests, Vol 13, Iss 282, p

2022 Volume 282

Abstract: Traditional tree improvement is cumbersome and costly. Our main objective was to assess the extent to which genomic data can currently accelerate and improve decision making in this field. We used diameter at breast height (DBH) and wood density (WD) ... ...

Abstract	Traditional tree improvement is cumbersome and costly. Our main objective was to assess the extent to which genomic data can currently accelerate and improve decision making in this field. We used diameter at breast height (DBH) and wood density (WD) data for 4430 tree genotypes and single-nucleotide polymorphism (SNP) data for 2446 tree genotypes. Pedigree reconstruction was performed using a combination of maximum likelihood parentage assignment and matching based on identity-by-state (IBS) similarity. In addition, we used best linear unbiased prediction (BLUP) methods to predict phenotypes using SNP markers (GBLUP), recorded pedigree information (ABLUP), and single-step “blended” BLUP (HBLUP) combining SNP and pedigree information. We substantially improved the accuracy of pedigree records, resolving the inconsistent parental information of 506 tree genotypes. This led to substantially increased predictive ability (i.e., by up to 87%) in HBLUP analyses compared to a baseline from ABLUP. Genomic prediction was possible across populations and within previously untested families with moderately large training populations ( N = 800–1200 tree genotypes) and using as few as 2000–5000 SNP markers. HBLUP was generally more effective than traditional ABLUP approaches, particularly after dealing appropriately with pedigree uncertainties. Our study provides evidence that genome-wide marker data can significantly enhance tree improvement. The operational implementation of genomic selection has started in radiata pine breeding in New Zealand, but further reductions in DNA extraction and genotyping costs may be required to realise the full potential of this approach.
Keywords	tree breeding ; pedigree reconstruction ; genomic selection ; genomic prediction ; single-step BLUP ; Pinus radiata ; Plant ecology ; QK900-989
Subject code	006
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article: Genomics-Enabled Management of Genetic Resources in Radiata Pine

Klápště, Jaroslav / Ismael, Ahmed / Paget, Mark / Graham, Natalie J. / Stovold, Grahame T. / Dungey, Heidi S. / Slavov, Gancho T.

Forests. 2022 Feb. 10, v. 13, no. 2

2022

Abstract	Traditional tree improvement is cumbersome and costly. Our main objective was to assess the extent to which genomic data can currently accelerate and improve decision making in this field. We used diameter at breast height (DBH) and wood density (WD) data for 4430 tree genotypes and single-nucleotide polymorphism (SNP) data for 2446 tree genotypes. Pedigree reconstruction was performed using a combination of maximum likelihood parentage assignment and matching based on identity-by-state (IBS) similarity. In addition, we used best linear unbiased prediction (BLUP) methods to predict phenotypes using SNP markers (GBLUP), recorded pedigree information (ABLUP), and single-step “blended” BLUP (HBLUP) combining SNP and pedigree information. We substantially improved the accuracy of pedigree records, resolving the inconsistent parental information of 506 tree genotypes. This led to substantially increased predictive ability (i.e., by up to 87%) in HBLUP analyses compared to a baseline from ABLUP. Genomic prediction was possible across populations and within previously untested families with moderately large training populations (N = 800–1200 tree genotypes) and using as few as 2000–5000 SNP markers. HBLUP was generally more effective than traditional ABLUP approaches, particularly after dealing appropriately with pedigree uncertainties. Our study provides evidence that genome-wide marker data can significantly enhance tree improvement. The operational implementation of genomic selection has started in radiata pine breeding in New Zealand, but further reductions in DNA extraction and genotyping costs may be required to realise the full potential of this approach.
Keywords	DNA ; Pinus radiata ; genomics ; genotyping ; marker-assisted selection ; parentage ; pedigree ; plant improvement ; prediction ; statistical analysis ; tree and stand measurements ; wood density ; New Zealand
Language	English
Dates of publication	2022-0210
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2527081-3
ISSN	1999-4907
ISSN	1999-4907
DOI	10.3390/f13020282
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Translational Control of the SigR-Directed Oxidative Stress Response in

Feeney, Morgan A / Chandra, Govind / Findlay, Kim C / Paget, Mark S B / Buttner, Mark J

mBio

2017 Volume 8, Issue 3

Abstract: The major oxidative stress response ... ...

Abstract	The major oxidative stress response in
MeSH term(s)	Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Codon, Initiator ; Gene Expression Regulation, Bacterial ; Operon ; Oxidative Stress ; Prokaryotic Initiation Factor-3/genetics ; Prokaryotic Initiation Factor-3/metabolism ; Regulon ; Sigma Factor/chemistry ; Sigma Factor/metabolism ; Streptomyces/genetics ; Streptomyces/physiology ; Transcription Factors/chemistry ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Bacterial Proteins ; Codon, Initiator ; Prokaryotic Initiation Factor-3 ; RsrA protein, Streptomyces coelicolor ; Sigma Factor ; Transcription Factors
Language	English
Publishing date	2017-06-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.00815-17
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Article ; Online: Accuracy of ECG chest electrode placements by paramedics: an observational study.

Gregory, Pete / Lodge, Stephen / Kilner, Tim / Paget, Suzy

British paramedic journal

2020 Volume 4, Issue 3, Page(s) 51–52

Abstract: ... practice. Correct positioning was determined against the Society for Cardiological Science and Technology's ... what they believed to be the correct positions on an anatomical diagram, and to describe the landmarks and positions ... to write down the landmarks and correct positions.: Conclusion: Our study identified a high level ...

Abstract	Introduction: The main aim of this study was to ascertain the accuracy of the chest lead placements by registered paramedics. Methods: Registered paramedics who attended the Emergency Services Show in Birmingham in September 2018 were invited to participate in this observational study. Participants were asked to place the chest electrodes on a human male model in accordance with their current practice. Correct positioning was determined against the Society for Cardiological Science and Technology's 2017 clinical guidelines for recording a standard 12-lead electrocardiogram, with a tolerance of 19 mm being deemed acceptable based upon previous studies. Participants were also asked to indicate what they believed to be the correct positions on an anatomical diagram, and to describe the landmarks and positions in writing. Results: A total of 52 eligible participants completed the study. Measurement of electrode placement in the craniocaudal and mediolateral planes showed a high level of inaccuracy, with 3/52 (5.8%) participants able to accurately place all chest leads. In leads V1-V3, the majority of incorrect placements were related to vertical displacement, with most participants able to identify the correct horizontal position. In V4, the tendency was to place the lead too low and to the left of the pre-determined position, while V5 tended to be below the expected positioning but in the correct horizontal alignment. There was a less defined pattern of error in V6, although vertical displacement was more likely than horizontal displacement. Only 1.9% of participants were able to correctly label the diagram and 1.9% were correctly able to write down the landmarks and correct positions. Conclusion: Our study identified a high level of variation in the placement of chest ECG electrodes, which could alter the morphology of the ECG. There was also a high degree of inaccuracy in the written components of the study, which suggests that underpinning knowledge is likely to be a major factor behind this variation. From a patient safety perspective, we would advocate that paramedics leave the chest electrodes in situ to allow hospital staff to assess the accuracy of the placements. Further consideration needs to be given to initial and ongoing training of ECG electrode placement to improve performance.
Language	English
Publishing date	2020-12-29
Publishing country	England
Document type	Journal Article
ISSN	1478-4726
ISSN (online)	1478-4726
DOI	10.29045/14784726.2019.12.4.3.51
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Article ; Online: Assessment of seasonality and normalization techniques for wastewater-based surveillance in Ontario, Canada.

Dhiyebi, Hadi A / Abu Farah, Joud / Ikert, Heather / Srikanthan, Nivetha / Hayat, Samina / Bragg, Leslie M / Qasim, Asim / Payne, Mark / Kaleis, Linda / Paget, Caitlyn / Celmer-Repin, Dominika / Folkema, Arianne / Drew, Stephen / Delatolla, Robert / Giesy, John P / Servos, Mark R

Frontiers in public health

2023 Volume 11, Page(s) 1186525

Abstract: Introduction: Wastewater-based surveillance is at the forefront of monitoring for community prevalence of COVID-19, however, continued uncertainty exists regarding the use of fecal indicators for normalization of the SARS-CoV-2 virus in wastewater. ... ...

Abstract	Introduction: Wastewater-based surveillance is at the forefront of monitoring for community prevalence of COVID-19, however, continued uncertainty exists regarding the use of fecal indicators for normalization of the SARS-CoV-2 virus in wastewater. Using three communities in Ontario, sampled from 2021-2023, the seasonality of a viral fecal indicator (pepper mild mottle virus, PMMoV) and the utility of normalization of data to improve correlations with clinical cases was examined. Methods: Wastewater samples from Warden, the Humber Air Management Facility (AMF), and Kitchener were analyzed for SARS-CoV-2, PMMoV, and crAssphage. The seasonality of PMMoV and flow rates were examined and compared by Season-Trend-Loess decomposition analysis. The effects of normalization using PMMoV, crAssphage, and flow rates were analyzed by comparing the correlations to clinical cases by episode date (CBED) during 2021. Results: Seasonal analysis demonstrated that PMMoV had similar trends at Humber AMF and Kitchener with peaks in January and April 2022 and low concentrations (troughs) in the summer months. Warden had similar trends but was more sporadic between the peaks and troughs for PMMoV concentrations. Flow demonstrated similar trends but was not correlated to PMMoV concentrations at Humber AMF and was very weak at Kitchener ( Discussion: Differences in seasonal trends in viral biomarkers caused by differences in sewershed characteristics (flow, input, etc.) may play a role in determining how effective normalization may be for improving correlations (or not). This study highlights the importance of assessing the influence of viral fecal indicators on normalized SARS-CoV-2 or other viruses of concern. Fecal indicators used to normalize the target of interest may help or hinder establishing trends with clinical outcomes of interest in wastewater-based surveillance and needs to be considered carefully across seasons and sites.
MeSH term(s)	Humans ; Ontario/epidemiology ; Wastewater-Based Epidemiological Monitoring ; Wastewater ; COVID-19/epidemiology ; SARS-CoV-2
Chemical Substances	Wastewater
Language	English
Publishing date	2023-08-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2711781-9
ISSN	2296-2565 ; 2296-2565
ISSN (online)	2296-2565
ISSN	2296-2565
DOI	10.3389/fpubh.2023.1186525
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Article: Bacterial redox sensors.

Green, Jeffrey / Paget, Mark S

Nature reviews. Microbiology

2004 Volume 2, Issue 12, Page(s) 954–966

Abstract: Redox reactions pervade living cells. They are central to both anabolic and catabolic metabolism. The ability to maintain redox balance is therefore vital to all organisms. Various regulatory sensors continually monitor the redox state of the internal ... ...

Abstract	Redox reactions pervade living cells. They are central to both anabolic and catabolic metabolism. The ability to maintain redox balance is therefore vital to all organisms. Various regulatory sensors continually monitor the redox state of the internal and external environments and control the processes that work to maintain redox homeostasis. In response to redox imbalance, new metabolic pathways are initiated, the repair or bypassing of damaged cellular components is coordinated and systems that protect the cell from further damage are induced. Advances in biochemical analyses are revealing a range of elegant solutions that have evolved to allow bacteria to sense different redox signals.
MeSH term(s)	Bacteria/metabolism ; Bacterial Proteins/metabolism ; Benzoquinones ; Cysteine/metabolism ; Flavin Mononucleotide/metabolism ; Flavin-Adenine Dinucleotide/metabolism ; Hemeproteins/metabolism ; Iron-Sulfur Proteins/metabolism ; NAD/metabolism ; NADP/metabolism ; Oxidation-Reduction ; Oxidative Stress ; Signal Transduction
Chemical Substances	Bacterial Proteins ; Benzoquinones ; Hemeproteins ; Iron-Sulfur Proteins ; NAD (0U46U6E8UK) ; Flavin-Adenine Dinucleotide (146-14-5) ; quinone (3T006GV98U) ; NADP (53-59-8) ; Flavin Mononucleotide (7N464URE7E) ; Cysteine (K848JZ4886)
Language	English
Publishing date	2004-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2139054-X
ISSN	1740-1534 ; 1740-1526
ISSN (online)	1740-1534
ISSN	1740-1526
DOI	10.1038/nrmicro1022
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Article: A novel sensor of NADH/NAD+ redox poise in Streptomyces coelicolor A3(2).

Brekasis, Dimitris / Paget, Mark S B

The EMBO journal

2003 Volume 22, Issue 18, Page(s) 4856–4865

Abstract: We describe the identification of Rex, a novel redox-sensing repressor that appears to be widespread among Gram-positive bacteria. In Streptomyces coelicolor Rex binds to operator (ROP) sites located upstream of several respiratory genes, including the ... ...

Abstract	We describe the identification of Rex, a novel redox-sensing repressor that appears to be widespread among Gram-positive bacteria. In Streptomyces coelicolor Rex binds to operator (ROP) sites located upstream of several respiratory genes, including the cydABCD and rex-hemACD operons. The DNA-binding activity of Rex appears to be controlled by the redox poise of the NADH/NAD+ pool. Using electromobility shift and surface plasmon resonance assays we show that NADH, but not NAD+, inhibits the DNA-binding activity of Rex. However, NAD+ competes with NADH for Rex binding, allowing Rex to sense redox poise over a range of NAD(H) concentrations. Rex is predicted to include a pyridine nucleotide-binding domain (Rossmann fold), and residues that might play key structural and nucleotide binding roles are highly conserved. In support of this, the central glycine in the signature motif (GlyXGlyXXGly) is shown to be essential for redox sensing. Rex homologues exist in most Gram-positive bacteria, including human pathogens such as Staphylococcus aureus, Listeria monocytogenes and Streptococcus pneumoniae.
MeSH term(s)	Amino Acid Sequence ; Animals ; Base Sequence ; Fungal Proteins/chemistry ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Gene Products, rex/chemistry ; Gene Products, rex/genetics ; Kinetics ; Molecular Sequence Data ; NAD/metabolism ; Operon ; Oxidation-Reduction ; Oxidoreductases/chemistry ; Oxidoreductases/metabolism ; Promoter Regions, Genetic ; Rats ; Repressor Proteins/chemistry ; Repressor Proteins/genetics ; Restriction Mapping ; Sequence Alignment ; Sequence Homology, Amino Acid ; Streptomyces/genetics ; Streptomyces/physiology
Chemical Substances	Fungal Proteins ; Gene Products, rex ; Repressor Proteins ; NAD (0U46U6E8UK) ; Oxidoreductases (EC 1.-)
Language	English
Publishing date	2003-09-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	586044-1
ISSN	1460-2075 ; 0261-4189
ISSN (online)	1460-2075
ISSN	0261-4189
DOI	10.1093/emboj/cdg453
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Article ; Online: The sigmaR regulon of Streptomyces coelicolor A32 reveals a key role in protein quality control during disulphide stress.

Kallifidas, Dimitris / Thomas, Derek / Doughty, Phillip / Paget, Mark S B

Microbiology (Reading, England)

2010 Volume 156, Issue Pt 6, Page(s) 1661–1672

Abstract: Diamide is an artificial disulphide-generating electrophile that mimics an oxidative shift in the cellular thiol-disulphide redox state (disulphide stress). The Gram-positive bacterium Streptomyces coelicolor senses and responds to disulphide stress ... ...

Abstract	Diamide is an artificial disulphide-generating electrophile that mimics an oxidative shift in the cellular thiol-disulphide redox state (disulphide stress). The Gram-positive bacterium Streptomyces coelicolor senses and responds to disulphide stress through the sigma(R)-RsrA system, which comprises an extracytoplasmic function (ECF) sigma factor and a redox-active anti-sigma factor. Known targets that aid in the protection and recovery from disulphide stress include the thioredoxin system and genes involved in producing the major thiol buffer mycothiol. Here we determine the global response to diamide in wild-type and sigR mutant backgrounds to understand the role of sigma(R) in this response and to reveal additional regulatory pathways that allow cells to cope with disulphide stress. In addition to thiol oxidation, diamide was found to cause protein misfolding and aggregation, which elicited the induction of the HspR heat-shock regulon. Although this response is sigma(R)-independent, sigma(R) does directly control Clp and Lon ATP-dependent AAA(+) proteases, which may partly explain the reduced ability of a sigR mutant to resolubilize protein aggregates. sigma(R) also controls msrA and msrB methionine sulphoxide reductase genes, implying that sigma(R)-RsrA is responsible for the maintenance of both cysteine and methionine residues during oxidative stress. This work shows that the sigma(R)-RsrA system plays a more significant role in protein quality control than previously realized, and emphasizes the importance of controlling the cellular thiol-disulphide redox balance.
MeSH term(s)	Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Diamide/pharmacology ; Disulfides/metabolism ; Heat-Shock Proteins/genetics ; Protein Folding/drug effects ; Proteins/genetics ; Proteins/metabolism ; RNA/genetics ; Regulon ; Repressor Proteins/genetics ; Sigma Factor/chemistry ; Sigma Factor/genetics ; Sigma Factor/metabolism ; Streptomyces coelicolor/drug effects ; Streptomyces coelicolor/genetics ; Streptomyces coelicolor/metabolism ; Transcription Factors/metabolism
Chemical Substances	Bacterial Proteins ; Disulfides ; Heat-Shock Proteins ; HspR protein, bacteria ; Proteins ; Repressor Proteins ; RsrA protein, Streptomyces coelicolor ; Sigma Factor ; Transcription Factors ; Diamide (10465-78-8) ; RNA (63231-63-0)
Language	English
Publishing date	2010-02-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1180712-x
ISSN	1465-2080 ; 1350-0872
ISSN (online)	1465-2080
ISSN	1350-0872
DOI	10.1099/mic.0.037804-0
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