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Article ; Online: Mapping structural and dynamic divergence across the MBOAT family.

Ansell, T Bertie / Healy, Megan / Coupland, Claire E / Sansom, Mark S P / Siebold, Christian

Structure (London, England : 1993)

2024

Abstract: Membrane-bound O-acyltransferases (MBOATs) are membrane-embedded enzymes that catalyze acyl chain transfer to a diverse group of substrates, including lipids, small molecules, and proteins. MBOATs share a conserved structural core, despite wide-ranging ... ...

Abstract	Membrane-bound O-acyltransferases (MBOATs) are membrane-embedded enzymes that catalyze acyl chain transfer to a diverse group of substrates, including lipids, small molecules, and proteins. MBOATs share a conserved structural core, despite wide-ranging functional specificity across both prokaryotes and eukaryotes. The structural basis of catalytic specificity, regulation and interactions with the surrounding environment remain uncertain. Here, we combine comparative molecular dynamics (MD) simulations with bioinformatics to assess molecular and interactional divergence across the family. In simulations, MBOATs differentially distort the bilayer depending on their substrate type. Additionally, we identify lipid binding sites surrounding reactant gates in the surrounding membrane. Complementary bioinformatic analyses reveal a conserved role for re-entrant loop-2 in MBOAT fold stabilization and a key hydrogen bond bridging DGAT1 dimerization. Finally, we predict differences in MBOAT solvation and water gating properties. These data are pertinent to the design of MBOAT-specific inhibitors that encompass dynamic information within cellular mimetic environments.
Language	English
Publishing date	2024-04-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1213087-4
ISSN	1878-4186 ; 0969-2126
ISSN (online)	1878-4186
ISSN	0969-2126
DOI	10.1016/j.str.2024.03.014
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Zs.A 4141: Show issues

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Article ; Online: Heterogeneous biological membranes regulate protein partitioning via fluctuating diffusivity.

Sakamoto, Ken / Akimoto, Takuma / Muramatsu, Mayu / Sansom, Mark S P / Metzler, Ralf / Yamamoto, Eiji

PNAS nexus

2023 Volume 2, Issue 8, Page(s) pgad258

Abstract: Cell membranes phase separate into ... ...

Abstract	Cell membranes phase separate into ordered
Language	English
Publishing date	2023-08-03
Publishing country	England
Document type	Journal Article
ISSN	2752-6542
ISSN (online)	2752-6542
DOI	10.1093/pnasnexus/pgad258
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Article ; Online: Using L. minor and C. elegans to assess the ecotoxicity of real-life contaminated soil samples and their remediation by clay- and carbon-based sorbents.

Rivenbark, Kelly J / Fawkes, Leanne S / Nikkhah, Hasan / Wang, Meichen / Sansom, Garett T / Beykal, Burcu / Wade, Terry L / Phillips, Timothy D

Environmental pollution (Barking, Essex : 1987)

2024 Volume 347, Page(s) 123762

Abstract: Toxic substances, such as polycyclic aromatic hydrocarbons (PAHs) and heavy metals, can accumulate in soil, posing a risk to human health and the environment. To reduce the risk of exposure, rapid identification and remediation of potentially hazardous ... ...

Abstract	Toxic substances, such as polycyclic aromatic hydrocarbons (PAHs) and heavy metals, can accumulate in soil, posing a risk to human health and the environment. To reduce the risk of exposure, rapid identification and remediation of potentially hazardous soils is necessary. Adsorption of contaminants by activated carbons and clay materials is commonly utilized to decrease the bioavailability of chemicals in soil and environmental toxicity in vitro, and this study aims to determine their efficacy in real-life soil samples. Two ecotoxicological models (Lemna minor and Caenorhabditis elegans) were used to test residential soil samples, known to contain an average of 5.3, 262, and 9.6 ppm of PAHs, lead, and mercury, for potential toxicity. Toxicity testing of these soils indicated that 86% and 58% of soils caused ≤50% inhibition of growth and survival of L. minor and C. elegans, respectively. Importantly, 3 soil samples caused ≥90% inhibition of growth in both models, and the toxicity was positively correlated with levels of heavy metals. These toxic soil samples were prioritized for remediation using activated carbon and SM-Tyrosine sorbents, which have been shown to immobilize PAHs and heavy metals, respectively. The inclusion of low levels of SM-Tyrosine protected the growth and survival of L. minor and C. elegans by 83% and 78%, respectively from the polluted soil samples while activated carbon offered no significant protection. These results also indicated that heavy metals were the driver of toxicity in the samples. Results from this study demonstrate that adsorption technologies are effective strategies for remediating complex, real-life soil samples contaminated with hazardous pollutants and protecting natural soil and groundwater resources and habitats. The results highlight the applicability of these ecotoxicological models as rapid screening tools for monitoring soil quality and verifying the efficacy of remediation practices.
MeSH term(s)	Animals ; Humans ; Clay ; Caenorhabditis elegans ; Charcoal ; Metals, Heavy/toxicity ; Metals, Heavy/analysis ; Polycyclic Aromatic Hydrocarbons/analysis ; Soil/chemistry ; Tyrosine ; Soil Pollutants/analysis ; Araceae
Chemical Substances	Clay (T1FAD4SS2M) ; Charcoal (16291-96-6) ; Metals, Heavy ; Polycyclic Aromatic Hydrocarbons ; Soil ; Tyrosine (42HK56048U) ; Soil Pollutants
Language	English
Publishing date	2024-03-11
Publishing country	England
Document type	Journal Article
ZDB-ID	280652-6
ISSN	1873-6424 ; 0013-9327 ; 0269-7491
ISSN (online)	1873-6424
ISSN	0013-9327 ; 0269-7491
DOI	10.1016/j.envpol.2024.123762
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Zs.A 2599: Show issues

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Article ; Online: Efficient disruption of the function of the mnuA nuclease gene using the endogenous CRISPR/Cas system in Mycoplasma gallisepticum.

Klose, Sara M / Wawegama, Nadeeka / Sansom, Fiona M / Marenda, Marc S / Browning, Glenn F

Veterinary microbiology

2022 Volume 269, Page(s) 109436

Abstract: ... the control of the vlhA1.1 promoter in a backbone plasmid carrying the oriC of M. imitans, and this plasmid ... was introduced into electrocompetent M. gallisepticum strain S6 cells. PCR assays targeting the ksgA ... that the M. gallisepticum CRISPR/Cas system can be programmed to cleave both DNA and RNA. ...

Abstract	Mycoplasmas are important animal pathogens, but the functions and roles of many of their genes in pathogenesis remain unclear, in large part because of the limited tools available for targeted mutagenesis in these bacteria. In this study we used the Mycoplasma gallisepticum CRISPR/Cas system to target a nuclease gene, MGA_0637 (mnuA), which is predicted to play a role in survival and virulence. Our strategy used simultaneous targeting of the ksgA kasugamycin resistance gene, as a mutation in this gene would not interfere with replication but would confer a readily detectable and selectable phenotype in transformants. A guide RNA plasmid, pKM-CRISPR, was constructed, with spacers targeting the ksgA and mnuA genes transcribed under the control of the vlhA1.1 promoter in a backbone plasmid carrying the oriC of M. imitans, and this plasmid was introduced into electrocompetent M. gallisepticum strain S6 cells. PCR assays targeting the ksgA gene, followed by Sanger sequence analyses of the phenotypically resistant transformants, detected polymorphisms within the targeted region of ksgA, confirming the activity of the endogenous CRISPR/Cas system. The nuclease activity of the kasugamycin resistant colonies was then assessed using zymogram assays. The complete or partial loss of nuclease activity in the majority of kasugamycin resistant isolates transformed with the CRISPR plasmid confirmed that the endogenous CRISPR/Cas system had effectively interfered with the function of both ksgA and mnuA genes. Sanger sequencing and RT-qPCR analyses of the mnuA gene suggested that the M. gallisepticum CRISPR/Cas system can be programmed to cleave both DNA and RNA.
MeSH term(s)	Animals ; CRISPR-Cas Systems ; Mycoplasma gallisepticum/genetics ; Plasmids/genetics
Language	English
Publishing date	2022-04-14
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	753154-0
ISSN	1873-2542 ; 0378-1135
ISSN (online)	1873-2542
ISSN	0378-1135
DOI	10.1016/j.vetmic.2022.109436
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Zs.A 2917: Show issues

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Article ; Online: Dimers Aren't Forever: CD80 Breaks up with PD-L1.

Sansom, David M / Walker, Lucy S K

Immunity

2020 Volume 51, Issue 6, Page(s) 972–974

Abstract: Targeting the CTLA-4 and PD-1 "checkpoints" is an effective treatment for a number of cancers. In this issue of Immunity, Hui et al. reveal that interaction between a CTLA-4 ligand, CD80, and its counterpart in the PD-1 pathway, PD-L1, affects both PD-1 ... ...

Abstract	Targeting the CTLA-4 and PD-1 "checkpoints" is an effective treatment for a number of cancers. In this issue of Immunity, Hui et al. reveal that interaction between a CTLA-4 ligand, CD80, and its counterpart in the PD-1 pathway, PD-L1, affects both PD-1 and CTLA-4 function, raising new questions about the biological effects of using checkpoint inhibitors alone and in combination.
MeSH term(s)	B7-1 Antigen ; B7-H1 Antigen ; CD28 Antigens ; CTLA-4 Antigen ; Programmed Cell Death 1 Receptor
Chemical Substances	B7-1 Antigen ; B7-H1 Antigen ; CD28 Antigens ; CTLA-4 Antigen ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2020-01-07
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2019.11.011
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Zs.A 4227: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 69: Show issues

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Article: Using the Mindfulness-Based Interventions: Teaching Assessment Criteria (MBI:TAC) in Supervision.

Evans, Alison / Griffith, Gemma M / Crane, Rebecca S / Sansom, Sophie A

Global advances in health and medicine

2021 Volume 10, Page(s) 2164956121989949

Abstract: The Mindfulness-Based Interventions: Teaching Assessment Criteria (MBI:TAC) is a useful framework for supporting teacher development in the context of mindfulness-based supervision (MBS). It offers a framework that enhances clarity, develops reflexive ... ...

Abstract	The Mindfulness-Based Interventions: Teaching Assessment Criteria (MBI:TAC) is a useful framework for supporting teacher development in the context of mindfulness-based supervision (MBS). It offers a framework that enhances clarity, develops reflexive practice, gives a structure for feedback, and supports learning. MBS is a key component of Mindfulness-Based Program (MBP) teacher training and ongoing good practice. Integrating the MBI:TAC within the MBS process adds value in a number of ways including: offering a shared language around MBP teaching skills and processes; framing the core pedagogical features of MBP teaching; enabling assessment of developmental stage; and empowering supervisees to be proactive in their own development. The paper lays out principles for integrating the MBI:TAC framework into MBS. The supervisor needs awareness of the ways in which the tool can add value, and the ways it can inadvertently interrupt learning. The tool enables skills clarification, but the learning process needs to remain open to spontaneous experiential discovery; it can enable structured feedback but space is also needed for open reflective feedback; and it can enable conceptual engagement with the teaching process but space is needed for the supervisee to experientially sense the teaching process. The tool needs to be introduced in a carefully staged way to create optimal conditions for learning at the various stages of the MBP teacher-training journey. Practical guidance is presented to consolidate and develop current practice. The principles and processes discussed can be generalized to other forms of reflective dialogue such as mentoring, tutoring and peer reflection groups.
Language	English
Publishing date	2021-02-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2709002-4
ISSN	2164-9561 ; 2164-957X
ISSN (online)	2164-9561
ISSN	2164-957X
DOI	10.1177/2164956121989949
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Article ; Online: A Review of Scheduling Strategies for Radiotherapy and Immune Checkpoint Inhibition in Locally Advanced Rectal Cancer.

Melissourgou-Syka, Lydia / Gillespie, Michael A / O'Cathail, Sean M / Sansom, Owen J / Steele, Colin W / Roxburgh, Campbell S D

Journal of immunotherapy and precision oncology

2023 Volume 6, Issue 4, Page(s) 187–197

Abstract: Colorectal cancer (CRC) is the third most common malignancy across the globe and, despite advances in treatment strategies, survival rates remain low. Rectal cancer (RC) accounts for most of these cases, and traditional management strategies for advanced ...

Abstract	Colorectal cancer (CRC) is the third most common malignancy across the globe and, despite advances in treatment strategies, survival rates remain low. Rectal cancer (RC) accounts for most of these cases, and traditional management strategies for advanced disease include total neoadjuvant therapy (TNT) with chemoradiotherapy followed by curative surgery. Unfortunately, approximately 10-15% of patients have no response to treatment or have recurrence at a short interval following radiotherapy. The introduction of immunotherapy in the form of immune checkpoint blockade (ICB) in metastatic colorectal cancer has improved clinical outcomes, yet most patients with RC present with microsatellite stable disease, which lacks the immune-rich microenvironment where ICB is most effective. There is evidence that combining radiotherapy with ICB can unlock the mechanisms that drive resistance in patients; however, the sequencing of these therapies is still debated. This review offers a comprehensive overview of clinical trials and preclinical models that use radiotherapy-immunotherapy combinations in RC in an attempt to extrapolate the ideal sequencing of the two treatment modalities. The results highlight the dearth of evidence to answer the question of whether ICB should be given before, during, or after radiotherapy, yet it is suggested that improving the relevance of our preclinical models will provide a platform with higher translational value and will lead to appropriate clinical trial designs.
Language	English
Publishing date	2023-12-02
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	3032799-4
ISSN	2590-017X ; 2666-2345
ISSN (online)	2590-017X
ISSN	2666-2345
DOI	10.36401/JIPO-23-10
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Article ; Online: Cancer risk associated with soil distribution of polycyclic aromatic hydrocarbons within three environmental justice neighborhoods in Houston, Texas

Sansom, Garett T. / Fawkes, Leanne S. / Thompson, Courtney M. / Losa, Lyssa M. / McDonald, Thomas J. / Chiu, Weihsueh A.

Environ Geochem Health. 2023 Feb., v. 45, no. 2 p.333-342

2023

Abstract: ... for the presence and concentration of the U.S. Environmental Protection Agency’s (USEPA) 7 Carcinogenic PAHs ...

Abstract	Residents and advocacy groups began voicing concerns over the environmental quality located in the neighborhoods of Kashmere Gardens, Fifth Ward, and Denver Harbor in Houston, TX, following the confirmation of a cancer cluster in 2019 and another in 2021. These neighborhoods are in close proximity to a railyard and former wood treatment plant known to have utilized coal tar creosote and contain polycyclic aromatic hydrocarbons (PAHs). This research took core soil samples in September and October 2020 from 46 sites to assess for the presence and concentration of the U.S. Environmental Protection Agency’s (USEPA) 7 Carcinogenic PAHs. Results showed the cumulative concentration of these PAHs in each sample was variable with a range of 13,767 ng/g to 328 ng/g and a mean of 2,517.2 ng/g ± 3122. A regional soil screening evaluation revealed that 40 of the 46 soil samples were in excess of the USEPAs most conservative screening levels of 1.0 × 10⁻⁶ increased cancer risk, but none exceeding levels considered actionable for remediation. This study is a fundamental first step for quantifying the environmental pollutants in this minority-majority community. Findings revealed a low risk of cancer risk based on current PAH concentrations alone but cannot assess contributions from other contaminants or from past, possibly higher, levels of contamination. Further research is needed to identify the potential casual pathways of the observed cancer cluster and to explore possible remediation needs.
Keywords	United States Environmental Protection Agency ; advocacy ; carcinogenicity ; creosote ; environmental quality ; remediation ; risk ; soil ; wood treatment ; Texas
Language	English
Dates of publication	2023-02
Size	p. 333-342.
Publishing place	Springer Netherlands
Document type	Article ; Online
ZDB-ID	52039-1
ISSN	1573-2983 ; 0142-7245 ; 0269-4042
ISSN (online)	1573-2983
ISSN	0142-7245 ; 0269-4042
DOI	10.1007/s10653-022-01245-5
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Article: Low radiodensity μCT scans to reveal detailed morphology of the termite leg and its subgenual organ

Sansom, Travers M. / Oberst, Sebastian / Richter, Adrian / Lai, Joseph C.S. / Saadatfar, Mohammad / Nowotny, Manuela / Evans, Theodore A.

Arthropod structure & development. 2022 June 09,

2022

Abstract: ... of a single stain of Lugol’s iodine solution (LS) to LS followed by Phosphotungstic acid (PTA) solutions (1 ... stains and scanning electron microscopy to exemplify the visualisation of their SGOs. The termite’s SGO ... μm, covering 60±4% of the leg’s cross-section and 90.4±5% of the residual haemolymph channel ...

Abstract	Termites sense tiny substrate-borne vibrations through subgenual organs (SGOs) located within their legs’ tibiae. Little is known about the SGOs’ structure and physical properties. We applied high-resolution (voxel size 0.45 μm) micro-computed tomography (μCT) to Australian termites, Coptotermes lacteus and Nasutitermes exitiosus (Hill) to test two staining techniques. We compared the effectiveness of a single stain of Lugol’s iodine solution (LS) to LS followed by Phosphotungstic acid (PTA) solutions (1% and 2%). We then present results of a soldier of Nasutitermes exitiosus combining μCT with LS + 2%PTS stains and scanning electron microscopy to exemplify the visualisation of their SGOs. The termite’s SGO due to its approximately oval shape was shown to have a maximum diameter of 60 μm and a minimum of 48 μm, covering 60±4% of the leg’s cross-section and 90.4±5% of the residual haemolymph channel. Additionally, the leg and residual haemolymph channel cross-sectional area decreased around the SGO by 33% and 73%, respectively. We hypothesise that this change in cross-sectional area amplifies the vibrations for the SGO. Since SGOs are directly connected to the cuticle, their mechanical properties and the geometric details identified here may enable new approaches to determine how termites sense micro-vibrations.
Keywords	Coptotermes ; Nasutitermes exitiosus ; arthropods ; geometry ; hemolymph ; micro-computed tomography ; phosphotungstic acid
Language	English
Dates of publication	2022-0609
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ZDB-ID	2001498-3
ISSN	1873-5495 ; 1467-8039
ISSN (online)	1873-5495
ISSN	1467-8039
DOI	10.1016/j.asd.2022.101191
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Article ; Online: Measuring CTLA-4-Dependent Suppressive Function in Regulatory T Cells.

Hou, Tie Zheng / Qureshi, Omar S / Sansom, David M

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

2019 Volume 1899, Page(s) 87–101

Abstract: Regulatory T cells (Treg) have a central role in controlling the activation of self-reactive T cells and maintaining peripheral tolerance in our body. Many effector mechanisms for Treg function have been described including a role for the protein CTLA-4 ... ...

Abstract	Regulatory T cells (Treg) have a central role in controlling the activation of self-reactive T cells and maintaining peripheral tolerance in our body. Many effector mechanisms for Treg function have been described including a role for the protein CTLA-4 which is constitutively expressed by these cells. Despite its importance, there is currently little consensus in the methods and protocols for studying CTLA-4 function, which is partially due to debate over CTLA-4 function itself. In this chapter, we outline protocols used in our lab to study CTLA-4 function, which have been generated based on the observation that CTLA-4 acts to physically remove and degrade its ligands expressed by antigen presenting cells. Accordingly, we provide protocols for isolation of human monocytes and their differentiation into dendritic cells (DC), purification of conventional and regulatory T-cell populations, and the assembly of CTLA-4-dependent Treg suppression assays. We hope that this will offer a reliable platform for dissecting the biology of CTLA-4 on Treg and for testing reagents aimed at modulating CTLA-4 function. Such assays are increasingly vital for the study of immune function in both healthy individuals and patients with a variety of autoimmune and immune dysregulation syndromes.
MeSH term(s)	Antigen-Presenting Cells/immunology ; CTLA-4 Antigen/genetics ; CTLA-4 Antigen/metabolism ; Cell Differentiation/genetics ; Cell Separation/methods ; Dendritic Cells/cytology ; Humans ; Ligands ; Monocytes/cytology ; T-Lymphocytes, Regulatory/cytology ; T-Lymphocytes, Regulatory/immunology
Chemical Substances	CTLA-4 Antigen ; CTLA4 protein, human ; Ligands
Language	English
Publishing date	2019-01-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-8938-6_7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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