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Article ; Online: ß-cell selective regulation of gene expression by nitric oxide.

Naatz, Aaron / Yeo, Chay Teng / Hogg, Neil / Corbett, John A

American journal of physiology. Regulatory, integrative and comparative physiology

2024

Abstract: Nitric oxide is produced at low micromolar levels following the induction of inducible nitric oxide synthase (iNOS) and is responsible for mediating the inhibitory actions of cytokines on glucose-stimulated insulin secretion by islets of Langerhans. It ... ...

Abstract	Nitric oxide is produced at low micromolar levels following the induction of inducible nitric oxide synthase (iNOS) and is responsible for mediating the inhibitory actions of cytokines on glucose-stimulated insulin secretion by islets of Langerhans. It is through the inhibition of mitochondrial oxidative metabolism, specifically aconitase and complex 4 of the electron transport chain, that nitric oxide inhibits insulin secretion. Nitric oxide also attenuates protein synthesis, induces DNA damage, activates DNA repair pathways, and stimulates stress responses (unfolded protein and heat shock) in β-cells. In this report, the time- and concentration-dependent effects of nitric oxide on the expression of 6 genes known to participate in the response of β-cells to this free radical were examined. The genes included
Language	English
Publishing date	2024-04-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	603839-6
ISSN	1522-1490 ; 0363-6119
ISSN (online)	1522-1490
ISSN	0363-6119
DOI	10.1152/ajpregu.00240.2023
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Article ; Online: Nitric oxide expands scope to cover hydrogen sulfide and carbon monoxide.

Hogg, Neil

Nitric oxide : biology and chemistry

2013 Volume 35, Page(s) 1

MeSH term(s)	Biochemistry ; Carbon Monoxide ; Humans ; Hydrogen Sulfide ; Nitric Oxide
Chemical Substances	Nitric Oxide (31C4KY9ESH) ; Carbon Monoxide (7U1EE4V452) ; Hydrogen Sulfide (YY9FVM7NSN)
Language	English
Publishing date	2013-11-30
Publishing country	United States
Document type	Editorial
ZDB-ID	1362794-6
ISSN	1089-8611 ; 1089-8603
ISSN (online)	1089-8611
ISSN	1089-8603
DOI	10.1016/j.niox.2013.06.003
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Zs.A 4677: Show issues

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Article ; Online: Centrifugation Removes a Population of Large Vesicles, or "Macroparticles," Intermediate in Size to RBCs and Microvesicles.

Larson, Michael C / Hogg, Neil / Hillery, Cheryl A

International journal of molecular sciences

2021 Volume 22, Issue 3

Abstract: Microparticles or microvesicles (MPs/MVs) are sub-cellular vesicles with a growing number of known biological functions. Microvesicles from a variety of parent cells within the vascular system increase in numerous pathological states. Red blood cell- ... ...

Abstract	Microparticles or microvesicles (MPs/MVs) are sub-cellular vesicles with a growing number of known biological functions. Microvesicles from a variety of parent cells within the vascular system increase in numerous pathological states. Red blood cell-derived MVs (RMVs) are relatively less studied than other types of circulating MVs despite red blood cells (RBCs) being the most abundant intravascular cell. This may be in part due the echoes of past misconceptions that RBCs were merely floating anucleate bags of hemoglobin rather than dynamic and responsive cells. The initial aim of this study was to maximize the concentration of RMVs derived from various blood or blood products by focusing on the optimal isolation conditions without creating more MVs from artificial manipulation. We found that allowing RBCs to sediment overnight resulted in a continuum in size of RBC membrane-containing fragments or vesicles extending beyond the 1 µm size limit suggested by many as the maximal size of an MV. Additionally, dilution and centrifugation factors were studied that altered the resultant MV population concentration. The heterogeneous size of RMVs was confirmed in mice models of hemolytic anemia. This methodological finding establishes a new paradigm in that it blurs the line between RBC, fragment, and RMV as well as suggests that the concentration of circulating RMVs may be widely underestimated given that centrifugation removes the majority of such RBC-derived membrane-containing particles.
MeSH term(s)	Anemia, Hemolytic/blood ; Anemia, Hemolytic/genetics ; Anemia, Hemolytic/pathology ; Animals ; Cell Lineage/genetics ; Cell-Derived Microparticles/genetics ; Centrifugation ; Erythrocyte Count ; Erythrocytes/cytology ; Hemoglobins/genetics ; Humans ; Mice
Chemical Substances	Hemoglobins
Language	English
Publishing date	2021-01-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22031243
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Article ; Online: Centrifugation Removes a Population of Large Vesicles, or “Macroparticles,” Intermediate in Size to RBCs and Microvesicles

Michael C. Larson / Neil Hogg / Cheryl A. Hillery

International Journal of Molecular Sciences, Vol 22, Iss 3, p

2021 Volume 1243

Abstract	Microparticles or microvesicles (MPs/MVs) are sub-cellular vesicles with a growing number of known biological functions. Microvesicles from a variety of parent cells within the vascular system increase in numerous pathological states. Red blood cell-derived MVs (RMVs) are relatively less studied than other types of circulating MVs despite red blood cells (RBCs) being the most abundant intravascular cell. This may be in part due the echoes of past misconceptions that RBCs were merely floating anucleate bags of hemoglobin rather than dynamic and responsive cells. The initial aim of this study was to maximize the concentration of RMVs derived from various blood or blood products by focusing on the optimal isolation conditions without creating more MVs from artificial manipulation. We found that allowing RBCs to sediment overnight resulted in a continuum in size of RBC membrane-containing fragments or vesicles extending beyond the 1 µm size limit suggested by many as the maximal size of an MV. Additionally, dilution and centrifugation factors were studied that altered the resultant MV population concentration. The heterogeneous size of RMVs was confirmed in mice models of hemolytic anemia. This methodological finding establishes a new paradigm in that it blurs the line between RBC, fragment, and RMV as well as suggests that the concentration of circulating RMVs may be widely underestimated given that centrifugation removes the majority of such RBC-derived membrane-containing particles.
Keywords	blood ; cell membrane microparticles ; circulating cell-derived microparticles ; cytoplasmic vesicles ; erythrocytes ; flow cytometry ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	612
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Sterile inflammation induces vasculopathy and chronic lung injury in murine sickle cell disease.

Rarick, Kevin R / Li, Keguo / Teng, Ru-Jeng / Jing, Xigang / Martin, Dustin P / Xu, Hao / Jones, Deron W / Hogg, Neil / Hillery, Cheryl A / Garcia, Guilherme / Day, Billy W / Naylor, Stephen / Pritchard, Kirkwood A

Free radical biology & medicine

2024 Volume 215, Page(s) 112–126

Abstract: Murine sickle cell disease (SCD) results in damage to multiple organs, likely mediated first by vasculopathy. While the mechanisms inducing vascular damage remain to be determined, nitric oxide bioavailability and sterile inflammation are both considered ...

Abstract	Murine sickle cell disease (SCD) results in damage to multiple organs, likely mediated first by vasculopathy. While the mechanisms inducing vascular damage remain to be determined, nitric oxide bioavailability and sterile inflammation are both considered to play major roles in vasculopathy. Here, we investigate the effects of high mobility group box-1 (HMGB1), a pro-inflammatory damage-associated molecular pattern (DAMP) molecule on endothelial-dependent vasodilation and lung morphometrics, a structural index of damage in sickle (SS) mice. SS mice were treated with either phosphate-buffered saline (PBS), hE-HMGB1-BP, an hE dual-domain peptide that binds and removes HMGB1 from the circulation via the liver, 1-[4-(aminocarbonyl)-2-methylphenyl]-5-[4-(1H-imidazol-1-yl)phenyl]-1H-pyrrole-2-propanoic acid (N6022) or N-acetyl-lysyltyrosylcysteine amide (KYC) for three weeks. Human umbilical vein endothelial cells (HUVEC) were treated with recombinant HMGB1 (r-HMGB1), which increases S-nitrosoglutathione reductase (GSNOR) expression by ∼80%, demonstrating a direct effect of HMGB1 to increase GSNOR. Treatment of SS mice with hE-HMGB1-BP reduced plasma HMGB1 in SS mice to control levels and reduced GSNOR expression in facialis arteries isolated from SS mice by ∼20%. These changes were associated with improved endothelial-dependent vasodilation. Treatment of SS mice with N6022 also improved vasodilation in SS mice suggesting that targeting GSNOR also improves vasodilation. SCD decreased protein nitrosothiols (SNOs) and radial alveolar counts (RAC) and increased GSNOR expression and mean linear intercepts (MLI) in lungs from SS mice. The marked changes in pulmonary morphometrics and GSNOR expression throughout the lung parenchyma in SS mice were improved by treating with either hE-HMGB1-BP or KYC. These data demonstrate that murine SCD induces vasculopathy and chronic lung disease by an HMGB1- and GSNOR-dependent mechanism and suggest that HMGB1 and GSNOR might be effective therapeutic targets for reducing vasculopathy and chronic lung disease in humans with SCD.
MeSH term(s)	Humans ; Animals ; Mice ; Lung Injury/etiology ; HMGB1 Protein/genetics ; Endothelial Cells/metabolism ; Anemia, Sickle Cell/drug therapy ; Anemia, Sickle Cell/genetics ; Inflammation ; Lung Diseases ; Vascular Diseases/etiology ; Benzamides ; Pyrroles
Chemical Substances	N6022 ; HMGB1 Protein ; Benzamides ; Pyrroles
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2024.01.052
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Zs.A 2109: Show issues

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Article ; Online: Detection of nitric oxide by electron paramagnetic resonance spectroscopy.

Hogg, Neil

Free radical biology & medicine

2010 Volume 49, Issue 2, Page(s) 122–129

Abstract: Electron paramagnetic resonance (EPR) spectroscopy has been used in a number of ways to study nitric oxide chemistry and biology. As an intrinsically stable and relatively unreactive diatomic free radical, the challenges of detecting this species by EPR ... ...

Abstract	Electron paramagnetic resonance (EPR) spectroscopy has been used in a number of ways to study nitric oxide chemistry and biology. As an intrinsically stable and relatively unreactive diatomic free radical, the challenges of detecting this species by EPR are somewhat different from those of transient radical species. This review gives a basic introduction to EPR spectroscopy and discusses its uses to assess and quantify nitric oxide formation in biological systems.
MeSH term(s)	Animals ; Biochemistry/methods ; Electron Spin Resonance Spectroscopy ; Free Radicals/metabolism ; Humans ; Nitric Oxide/metabolism
Chemical Substances	Free Radicals ; Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2010-03-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2010.03.009
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Zs.A 2109: Show issues

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Article ; Online: PRMT1 acts as a suppressor of MHC-I and anti-tumor immunity.

Djajawi, Tirta M / Pijpers, Lizzy / Srivaths, Akash / Chisanga, David / Chan, Kok Fei / Hogg, Simon J / Neil, Liam / Rivera, Sarahi Mendoza / Bartonicek, Nenad / Ellis, Sarah L / Lim Kam Sian, Terry C C / Faridi, Pouya / Liao, Yang / Pal, Bhupinder / Behren, Andreas / Shi, Wei / Vervoort, Stephin J / Johnstone, Ricky W / Kearney, Conor J

Cell reports

2024 Volume 43, Issue 3, Page(s) 113831

Abstract: Cancer immunotherapies have demonstrated remarkable success; however, the majority of patients do not respond or develop resistance. Here, we conduct epigenetic gene-targeted CRISPR-Cas9 screens to identify epigenomic factors that limit ... ...

Abstract	Cancer immunotherapies have demonstrated remarkable success; however, the majority of patients do not respond or develop resistance. Here, we conduct epigenetic gene-targeted CRISPR-Cas9 screens to identify epigenomic factors that limit CD8
MeSH term(s)	Humans ; CD8-Positive T-Lymphocytes/metabolism ; Protein-Arginine N-Methyltransferases/genetics ; Protein-Arginine N-Methyltransferases/metabolism ; Histocompatibility Antigens Class I/genetics ; Immunity, Cellular ; Interferon-gamma/metabolism ; Melanoma/pathology ; Repressor Proteins/genetics ; Repressor Proteins/metabolism
Chemical Substances	Protein-Arginine N-Methyltransferases (EC 2.1.1.319) ; Histocompatibility Antigens Class I ; Interferon-gamma (82115-62-6) ; PRMT1 protein, human (EC 2.1.1.319) ; Repressor Proteins
Language	English
Publishing date	2024-02-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2024.113831
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Article ; Online: A review of UK undergraduate surgical curricula and teaching methods with an analysis of the university of Dundee (2011–2021)

Andrew Keenlyside / Neil Harrison / Roderick McLeod / Gordon Hogg / Kismet Hossain-Ibrahim

Health Sciences Review, Vol 4, Iss , Pp 100048- (2022)

2022

Abstract: Introduction: This review discussed the current state of undergraduate surgical education in UK medical schools with focus on changes over the previous decade (2011–2021). An analysis of theatre etiquette and basic surgical skills (BSS) courses from the ... ...

Abstract	Introduction: This review discussed the current state of undergraduate surgical education in UK medical schools with focus on changes over the previous decade (2011–2021). An analysis of theatre etiquette and basic surgical skills (BSS) courses from the University of Dundee undergraduate curriculum was also undertaken, with comparison to the literature. Materials and methods: A PubMed search using the quire “(undergraduate) AND (medicine) AND (Surgical) AND (teaching) AND (UK)” returned 155 publications. These were screened for relevance to yield the 100 publications discussed in this review. Analysis of student feedback (2016 – 2019) was carried out for BSS and theatre etiquette courses. Results: There exists a lack of consensus around the undergraduate curricula with extreme variation in teaching and clinical exposure by speciality and medical school. These are aided by the widespread adoption of simulation-based learning and non-technical skills teaching. Most teaching is conducted in transitional programmes to prepare students for surgical attachments with skills teaching focused on fourth- and fifth-year students. Scrubbing, gowning, gloving, and suturing are all often taught briefly and inconsistently with little follow up.A wide variety of novel techniques including near peer assisted, targeted basic surgical skills (BSS) courses and student opportunities, including mentorship and conferences have been found to be effective but are often limited to a single institution. Conclusions: Consensus amongst the existing literature highlights an urgent need for reform of surgical education to ensure patient safety and graduate competency. The University of Dundee runs a theatre etiquette and BSS courses which produces results which indicate a high degree in confidence subjective outcomes. There is a wealth of subjective and non-specific data with infrequent objective comparison between modern teaching modalities. The deficiency of undergraduate surgical teaching presents an opportunity to re-establish curricula ...
Keywords	Undergraduate ; Surgical ; Education ; Simulation ; Review ; Medicine ; R
Subject code	370
Language	English
Publishing date	2022-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Nitric Oxide Circumvents Virus-Mediated Metabolic Regulation during Human Cytomegalovirus Infection.

Mokry, Rebekah L / Schumacher, Megan L / Hogg, Neil / Terhune, Scott S

mBio

2020 Volume 11, Issue 6

Abstract: Nitric oxide is a versatile and critical effector molecule that can modulate many cellular functions. Although recognized as a regulator of infections, the inhibitory mechanism of nitric oxide against human cytomegalovirus (HCMV) replication remains ... ...

Abstract	Nitric oxide is a versatile and critical effector molecule that can modulate many cellular functions. Although recognized as a regulator of infections, the inhibitory mechanism of nitric oxide against human cytomegalovirus (HCMV) replication remains elusive. We demonstrate that nitric oxide attenuates viral replication by interfering with HCMV-mediated modulation of several cellular processes. Nitric oxide exposure reduced HCMV genome synthesis and infectious viral progeny with cell-type-dependent differences observed. Mitochondrial respiration was severely reduced in both uninfected and HCMV-infected cells during exposure with little impact on ATP levels indicating changes in cellular metabolism. Metabolomics identified significantly altered small molecules in multiple pathways during nitric oxide exposure including nucleotide biosynthesis, tricarboxylic acid (TCA) cycle, and glutamine metabolism. Glutathione metabolites were increased coinciding with a reduction in the glutathione precursor glutamine. This shift was accompanied by increased antioxidant enzymes. Glutamine deprivation mimicked defects in HCMV replication and mitochondrial respiration observed during nitric oxide exposure. These data suggest that nitric oxide limits glutaminolysis by shuttling glutamine to glutathione synthesis. In addition, lipid intermediates were severely altered, which likely contributes to the observed increase in defective viral particles. Nitric oxide disrupts multiple cellular processes, and we had limited success in rescuing replication defects by supplementing with metabolic intermediates. Our studies indicate that nitric oxide attenuation of HCMV is multifactorial with interference in viral manipulation of cellular metabolism playing a central role.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Cell Line ; Citric Acid Cycle ; Cytomegalovirus/genetics ; Cytomegalovirus/physiology ; Cytomegalovirus Infections/immunology ; Cytomegalovirus Infections/metabolism ; Cytomegalovirus Infections/virology ; Glutamine/metabolism ; Glutathione/metabolism ; Host-Pathogen Interactions ; Humans ; Mitochondria/metabolism ; Nitric Oxide/immunology ; Nitric Oxide/metabolism ; Virus Replication
Chemical Substances	Glutamine (0RH81L854J) ; Nitric Oxide (31C4KY9ESH) ; Adenosine Triphosphate (8L70Q75FXE) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2020-12-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.02630-20
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Article: Red meat and colon cancer: heme proteins and nitrite in the gut. A commentary on "diet-induced endogenous formation of nitroso compounds in the GI tract".

Hogg, Neil

Free radical biology & medicine

2007 Volume 43, Issue 7, Page(s) 1037–1039

MeSH term(s)	Colonic Neoplasms/etiology ; Colonic Neoplasms/pathology ; Diet ; Gastrointestinal Tract/metabolism ; Heme/isolation & purification ; Heme/pharmacology ; Hemeproteins/metabolism ; Humans ; Meat ; Nitrites/metabolism ; Nitroso Compounds/metabolism
Chemical Substances	Hemeproteins ; Nitrites ; Nitroso Compounds ; Heme (42VZT0U6YR)
Language	English
Publishing date	2007-10-01
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2007.07.006
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