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Article ; Online: DNA sensing in cancer: Pro-tumour and anti-tumour functions of cGAS-STING signalling.

Wheeler, Otto P G / Unterholzner, Leonie

2023 Volume 67, Issue 6, Page(s) 905–918

Abstract: The DNA sensor cGAS (cyclic GMP-AMP synthase) and its adaptor protein STING (Stimulator of Interferon Genes) detect the presence of cytosolic DNA as a sign of infection or damage. In cancer cells, this pathway can be activated through persistent DNA ... ...

Abstract	The DNA sensor cGAS (cyclic GMP-AMP synthase) and its adaptor protein STING (Stimulator of Interferon Genes) detect the presence of cytosolic DNA as a sign of infection or damage. In cancer cells, this pathway can be activated through persistent DNA damage and chromosomal instability, which results in the formation of micronuclei and the exposure of DNA fragments to the cytosol. DNA damage from radio- or chemotherapy can further activate DNA sensing responses, which may occur in the cancer cells themselves or in stromal and immune cells in the tumour microenvironment (TME). cGAS-STING signalling results in the production of type I interferons, which have been linked to immune cell infiltration in 'hot' tumours that are susceptible to immunosurveillance and immunotherapy approaches. However, recent research has highlighted the complex nature of STING signalling, with tumours having developed mechanisms to evade and hijack this signalling pathway for their own benefit. In this mini-review we will explore how cGAS-STING signalling in different cells in the TME can promote both anti-tumour and pro-tumour responses. This includes the role of type I interferons and the second messenger cGAMP in the TME, and the influence of STING signalling on local immune cell populations. We examine how alternative signalling cascades downstream of STING can promote chronic interferon signalling, the activation of the transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and the production of inflammatory cytokines, which can have pro-tumour functions. An in-depth understanding of DNA sensing in different cell contexts will be required to harness the anti-tumour functions of STING signalling.
MeSH term(s)	Humans ; Immunity, Innate/genetics ; DNA/metabolism ; Nucleotidyltransferases/genetics ; Nucleotidyltransferases/metabolism ; Interferon Type I/genetics ; Interferon Type I/metabolism ; Neoplasms/therapy ; Tumor Microenvironment
Chemical Substances	DNA (9007-49-2) ; Nucleotidyltransferases (EC 2.7.7.-) ; Interferon Type I
Language	English
Publishing date	2023-08-03
Publishing country	England
Document type	Review ; Journal Article
ISSN	1744-1358 ; 0071-1365
ISSN (online)	1744-1358
ISSN	0071-1365
DOI	10.1042/EBC20220241
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Debunking Murray‐Darling Basin water trade myths

Wheeler, Sarah Ann

Australian Journal of Agricultural and Resource Economics. 2022 Oct., v. 66, no. 4 p.797-821

2022

Abstract: ... issues that need addressing (e.g., water property entitlements for indigenous stakeholders ...

Abstract	Australia, and particularly the Murray–Darling Basin (MDB), has the most mature and adopted water markets globally. Water trading is an important policy tool to deal with water scarcity issues, demonstrating allocative, dynamic and productive efficiency benefits. At the same time, water markets have been controversial in Australia. Markets have been blamed for a range of issues, including claims of unsustainability, inequity, farm bankruptcy, farmer distress and farm exit. This study reviews the MDB water trade literature and finds little evidence to support such myths. Arguably, the biggest misconception is that critics do not separate water markets from the meta‐governance institutional structures that define them. Perceived water market failures are often due to governance issues – not water trade per se. This is not to say that market failure does not exist, it does, and indeed, there are also serious distributional issues that need addressing (e.g., water property entitlements for indigenous stakeholders). As such, water market design and governance need to adapt and evolve as problems arise and the market matures. However, in an era of increasing water scarcity, enabling water trade remains one of the most important instruments available to assist in water sharing, reallocation and farm adaptation to climate change.
Keywords	bankruptcy ; basins ; climate change ; distress ; farmers ; farms ; governance ; issues and policy ; markets ; stakeholders ; trade ; water shortages ; Australia
Language	English
Dates of publication	2022-10
Size	p. 797-821.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	REVIEW
ZDB-ID	1387184-5
ISSN	1364-985X
ISSN	1364-985X
DOI	10.1111/1467-8489.12490
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Gephyrocapsa huxleyi (Emiliania huxleyi) as a model system for coccolithophore biology

Wheeler, Glen L. / Sturm, Daniela / Langer, Gerald

Journal of Phycology. 2023 Dec., v. 59, no. 6 p.1123-1129

2023

Abstract: ... Gephyrocapsa huxleyi. G. huxleyi has a cosmopolitan distribution, occupying coastal and oceanic environments ... across the globe, and is the most abundant coccolithophore in modern oceans. Research in G. huxleyi has ... In this perspective, we summarize the key advances made using G. huxleyi and examine the emerging tools for research ...

Abstract	Coccolithophores are the most abundant calcifying organisms in modern oceans and are important primary producers in many marine ecosystems. Their ability to generate a cellular covering of calcium carbonate plates (coccoliths) plays a major role in marine biogeochemistry and the global carbon cycle. Coccolithophores also play an important role in sulfur cycling through the production of the climate‐active gas dimethyl sulfide. The primary model organism for coccolithophore research is Emiliania huxleyi, now named Gephyrocapsa huxleyi. G. huxleyi has a cosmopolitan distribution, occupying coastal and oceanic environments across the globe, and is the most abundant coccolithophore in modern oceans. Research in G. huxleyi has identified many aspects of coccolithophore biology, from cell biology to ecological interactions. In this perspective, we summarize the key advances made using G. huxleyi and examine the emerging tools for research in this model organism. We discuss the key steps that need to be taken by the research community to advance G. huxleyi as a model organism and the suitability of other species as models for specific aspects of coccolithophore biology.
Keywords	Emiliania huxleyi ; algology ; biogeochemistry ; calcium carbonate ; cell biology ; dimethyl sulfide ; global carbon budget ; sulfur
Language	English
Dates of publication	2023-12
Size	p. 1123-1129.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	281226-5
ISSN	1529-8817 ; 0022-3646
ISSN (online)	1529-8817
ISSN	0022-3646
DOI	10.1111/jpy.13404
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Parsimony optimization of phylogenetic networks

Wheeler, Ward C. / Washburn, Alexander J.

Cladistics. 2023 Oct., v. 39, no. 5 p.456-474

2023

Abstract: An algorithm is described for the optimization of character data (e.g. qualitative, nucleic acid ...

Abstract	An algorithm is described for the optimization of character data (e.g. qualitative, nucleic acid sequence) on softwired phylogenetic networks. The algorithm presented here is an extension of those developed for trees under the parsimony criterion and can form the basis for phylogenetic network search procedures. Although the problem is (in general) an NP‐Hard optimization, the resolution‐based algorithm we describe here capitalizes on the significant amount of shared structure in sub‐graphs containing network edges, reducing the execution time and allowing for the analysis of empirical datasets.
Keywords	algorithms ; data collection ; nucleotide sequences ; phylogeny
Language	English
Dates of publication	2023-10
Size	p. 456-474.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	1462608-1
ISSN	1096-0031 ; 0748-3007
ISSN (online)	1096-0031
ISSN	0748-3007
DOI	10.1111/cla.12552
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Article ; Online: Cannabidiol Oil Ingested as Sublingual Drops or Within Gelatin Capsules Shows Similar Pharmacokinetic Profiles in Healthy Males.

Johnson, Drusus A / Funnell, Mark P / Heaney, Liam M / Cable, Thomas G / Wheeler, Patrick C / Bailey, Stephen J / Clifford, Tom / James, Lewis J

Cannabis and cannabinoid research

2023

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2023-09-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2867624-5
ISSN	2378-8763 ; 2578-5125
ISSN (online)	2378-8763
ISSN	2578-5125
DOI	10.1089/can.2023.0117
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Article ; Online: Simultaneous Measurement of Endothelial Cell Proliferation and Cell Cycle Stage Using Flow Cytometry.

Lynam, Eleanor G / Lane, James A E / Finding, Elizabeth J T / Wheeler-Jones, Caroline P D

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2475, Page(s) 223–228

Abstract: Endothelial cell proliferation rate is an important indicator of vascular health. Being able to detect the rate of endothelial cell proliferation, or cell cycle disturbances after intervention is a valuable tool for analysing any beneficial or ... ...

Abstract	Endothelial cell proliferation rate is an important indicator of vascular health. Being able to detect the rate of endothelial cell proliferation, or cell cycle disturbances after intervention is a valuable tool for analysing any beneficial or detrimental effects of treatments in vitro. Here, we describe a straightforward flow cytometric-based method of proliferation and cell cycle tracking that can be performed on human endothelial cells in culture over several days.
MeSH term(s)	Cell Cycle ; Cell Division ; Cell Proliferation ; Endothelial Cells ; Flow Cytometry/methods ; Humans
Language	English
Publishing date	2022-04-22
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2217-9_16
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Article ; Online: The Lung Microbiome Predicts Mortality and Response to Azithromycin in Lung Transplant Patients with Chronic Rejection.

Combs, Michael P / Luth, Jenna E / Falkowski, Nicole R / Wheeler, David S / Walker, Natalie M / Erb-Downward, John R / Wakeam, Elliot / Sjoding, Michael W / Dunlap, Daniel G / Admon, Andrew J / Dickson, Robert P / Lama, Vibha N

American journal of respiratory and critical care medicine

2024

Abstract: Rationale: Chronic lung allograft dysfunction (CLAD) is the leading cause of death following lung transplant, and azithromycin has variable efficacy in CLAD. The lung microbiome is a risk factor for developing CLAD, but the relationship between lung ... ...

Abstract	Rationale: Chronic lung allograft dysfunction (CLAD) is the leading cause of death following lung transplant, and azithromycin has variable efficacy in CLAD. The lung microbiome is a risk factor for developing CLAD, but the relationship between lung dysbiosis, pulmonary inflammation, and allograft dysfunction remains poorly understood. Whether lung microbiota predict outcomes or modify treatment response Objectives: To determine whether lung microbiota predict post-CLAD outcomes and clinical response to azithromycin. Methods: Retrospective cohort study using acellular bronchoalveolar lavage (BAL) fluid prospectively collected from lung transplant recipients within 90 days of CLAD onset. Lung microbiota were characterized using 16S rRNA gene sequencing and ddPCR. In two additional cohorts, causal relationships of dysbiosis and inflammation were evaluated by comparing lung microbiota with CLAD-associated cytokines and measuring Measurements and main results: Patients with higher bacterial burden had shorter post-CLAD survival, independent of CLAD phenotype, azithromycin treatment, and relevant covariates. Azithromycin treatment improved survival in patients with high bacterial burden, but had negligible impact on patients with low or moderate burden. Lung bacterial burden was positively associated with CLAD-associated cytokines, and Conclusions: In lung transplant patients with chronic rejection, increased lung bacterial burden is an independent risk factor for mortality and predicts clinical response to azithromycin. Lung bacterial dysbiosis is associated with alveolar inflammation and may be promoted by underlying lung allograft dysfunction.
Language	English
Publishing date	2024-01-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202308-1326OC
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Article ; Online: High-throughput prioritization of target proteins for development of new antileishmanial compounds.

Azevedo, Lucas G / Sosa, Ezequiel / de Queiroz, Artur T L / Barral, Aldina / Wheeler, Richard J / Nicolás, Marisa F / Farias, Leonardo P / Do Porto, Dario Fernández / Ramos, Pablo Ivan P

International journal for parasitology. Drugs and drug resistance

2024 Volume 25, Page(s) 100538

Abstract: Leishmaniasis, a vector-borne disease, is caused by the infection of Leishmania spp., obligate intracellular protozoan parasites. Presently, human vaccines are unavailable, and the primary treatment relies heavily on systemic drugs, often presenting with ...

Abstract	Leishmaniasis, a vector-borne disease, is caused by the infection of Leishmania spp., obligate intracellular protozoan parasites. Presently, human vaccines are unavailable, and the primary treatment relies heavily on systemic drugs, often presenting with suboptimal formulations and substantial toxicity, making new drugs a high priority for LMIC countries burdened by the disease, but a low priority in the agenda of most pharmaceutical companies due to unattractive profit margins. New ways to accelerate the discovery of new, or the repositioning of existing drugs, are needed. To address this challenge, our study aimed to identify potential protein targets shared among clinically-relevant Leishmania species. We employed a subtractive proteomics and comparative genomics approach, integrating high-throughput multi-omics data to classify these targets based on different druggability metrics. This effort resulted in the ranking of 6502 ortholog groups of protein targets across 14 pathogenic Leishmania species. Among the top 20 highly ranked groups, metabolic processes known to be attractive drug targets, including the ubiquitination pathway, aminoacyl-tRNA synthetases, and purine synthesis, were rediscovered. Additionally, we unveiled novel promising targets such as the nicotinate phosphoribosyltransferase enzyme and dihydrolipoamide succinyltransferases. These groups exhibited appealing druggability features, including less than 40% sequence identity to the human host proteome, predicted essentiality, structural classification as highly druggable or druggable, and expression levels above the 50th percentile in the amastigote form. The resources presented in this work also represent a comprehensive collection of integrated data regarding trypanosomatid biology.
Language	English
Publishing date	2024-04-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2751132-7
ISSN	2211-3207 ; 2211-3207
ISSN (online)	2211-3207
ISSN	2211-3207
DOI	10.1016/j.ijpddr.2024.100538
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Article ; Online: Is proton beam therapy always better than photon irradiation? Lessons from two cases.

Li, Michelle P / Yeo, Adam / Gunewardena, Roshini / Drum, Gabrielle / Wiltshire, Kirsty / Phillips, Claire / Sia, Joseph / Wheeler, Greg / Hall, Lisa

Journal of medical radiation sciences

2024 Volume 71 Suppl 2, Page(s) 90–98

Abstract: Proton beam therapy (PBT) is increasingly used to treat cancers, especially in the paediatric and adolescent and young adult (AYA) population. As PBT becomes more accessible, determining when PBT should be used instead of photon irradiation can be ... ...

Abstract	Proton beam therapy (PBT) is increasingly used to treat cancers, especially in the paediatric and adolescent and young adult (AYA) population. As PBT becomes more accessible, determining when PBT should be used instead of photon irradiation can be difficult. There is a need to balance patient, tumour and treatment factors when making this decision. Comparing the dosimetry between these two modalities plays an important role in this process. PBT can reduce low to intermediate doses to organs at risk (OAR), but photon irradiation has its dosimetric advantages. We present two cases with brain tumours, one paediatric and one AYA, in which treatment plan comparison between photons and protons showed dosimetric advantages of photon irradiation. The first case was an 18-month-old child diagnosed with posterior fossa ependymoma requiring adjuvant radiotherapy. Photon irradiation using volumetric modulated arc therapy (VMAT) had lower doses to the hippocampi but higher doses to the pituitary gland. The second case was a 21-year-old with an optic pathway glioma. There was better sparing of the critical optic structures and pituitary gland using fractionated stereotactic radiation therapy over PBT. The dosimetric advantages of photon irradiation over PBT have been demonstrated in these cases. This highlights the role of proton-to-photon comparative treatment planning to better understand which patients might benefit from photon irradiation versus PBT.
MeSH term(s)	Adolescent ; Humans ; Child ; Infant ; Young Adult ; Adult ; Proton Therapy ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Intensity-Modulated ; Radiosurgery
Language	English
Publishing date	2024-03-20
Publishing country	United States
Document type	Case Reports
ZDB-ID	2734841-6
ISSN	2051-3909 ; 2051-3909
ISSN (online)	2051-3909
ISSN	2051-3909
DOI	10.1002/jmrs.773
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Article ; Online: Severe muscle bleeds in children and young adults with hemophilia A on emicizumab prophylaxis: Real-world retrospective multi-institutional cohort.

Batsuli, Glaivy / Wheeler, Allison P / Weyand, Angela C / Sidonio, Robert F / Young, Guy

American journal of hematology

2023 Volume 98, Issue 10, Page(s) E285–E287

MeSH term(s)	Child ; Humans ; Young Adult ; Antibodies, Bispecific/adverse effects ; Factor VIII ; Hemophilia A/complications ; Hemophilia A/drug therapy ; Hemorrhage/etiology ; Hemorrhage/prevention & control ; Muscles ; Retrospective Studies
Chemical Substances	Antibodies, Bispecific ; emicizumab (7NL2E3F6K3) ; Factor VIII (9001-27-8)
Language	English
Publishing date	2023-07-20
Publishing country	United States
Document type	Letter ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	196767-8
ISSN	1096-8652 ; 0361-8609
ISSN (online)	1096-8652
ISSN	0361-8609
DOI	10.1002/ajh.27039
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