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Article ; Online: Community outreach initiatives in dermatology: cross-sectional study.

Fritsche, Madelaine / Maglakelidze, Natella / Zaenglein, Andrea / Lam, Charlene

2023 Volume 315, Issue 9, Page(s) 2693–2695

MeSH term(s)	Humans ; Dermatology/education ; Cross-Sectional Studies ; Community-Institutional Relations ; Curriculum ; Internship and Residency ; Surveys and Questionnaires
Language	English
Publishing date	2023-05-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	130131-7
ISSN	1432-069X ; 0340-3696
ISSN (online)	1432-069X
ISSN	0340-3696
DOI	10.1007/s00403-023-02629-y
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Article ; Online: AIRE Deficiency Leads to the Development of Alopecia Areata‒Like Lesions in Mice.

Maglakelidze, Natella / Gao, Ting / Feehan, Robert P / Hobbs, Ryan P

The Journal of investigative dermatology

2022 Volume 143, Issue 4, Page(s) 578–587.e3

Abstract: Alopecia areata (AA) is an autoimmune hair loss disorder with no cure. Patients with sequence variation in AIRE are 15 times more likely to develop AA than the general population, yet the roles of AIRE in AA pathogenesis are unknown. In this study, we ... ...

Abstract	Alopecia areata (AA) is an autoimmune hair loss disorder with no cure. Patients with sequence variation in AIRE are 15 times more likely to develop AA than the general population, yet the roles of AIRE in AA pathogenesis are unknown. In this study, we report that 62% of C57BL/6J female Aire
MeSH term(s)	Humans ; Female ; Mice ; Animals ; Alopecia Areata ; CD8-Positive T-Lymphocytes ; Interleukin Receptor Common gamma Subunit ; Polyendocrinopathies, Autoimmune/pathology ; Mice, Inbred C57BL ; Hair Follicle/pathology
Chemical Substances	Interleukin Receptor Common gamma Subunit
Language	English
Publishing date	2022-10-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2022.09.656
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Article ; Online: A Review: Does Complement or the Contact System Have a Role in Protection or Pathogenesis of COVID-19?

Maglakelidze, Natella / Manto, Kristen M / Craig, Timothy J

Pulmonary therapy

2020 Volume 6, Issue 2, Page(s) 169–176

Abstract: Introduction: COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory ... ...

Abstract	Introduction: COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory arrest, and death. At present, anti-IL-6, antiviral therapy, convalescent plasma, hydroxychloroquine, and azithromycin among others are being investigated as potential treatments for COVID-19. As the disease etiology and precise therapeutic interventions are still not definitively defined, we wanted to review the roles that complement and the contact system may have in either the treatment or pathogenesis of the disease. Methods: We searched the recent literature (PubMed) on complement and coronavirus; contact system and coronavirus; bradykinin and coronavirus; and angiotensin receptor and coronavirus. The manuscript complies with ethics guidelines and was deemed exempt from institutional review board approval according to Human Subjects Protection Office guidelines. Results: Mouse models are available for the study of coronavirus and complement. Although complement is effective in protecting against many viruses, it does not seem to be protective against coronavirus. C3 knockout mice infected with SARS-CoV had less lung disease than wild-type mice, suggesting that complement may play a role in coronavirus pathogenesis. Some evidence suggests that the observed pulmonary edema may be bradykinin-induced and could be the reason that corticosteroids, antihistamines, and other traditional interventions for edema are not effective. Angiotensin-converting enzyme 2 (ACE2) is a co-receptor for SARS-CoV-2, and studies thus far have not concluded a benefit or risk associated with the use of either ACE-inhibitors or angiotensin receptor antagonists. Activation of complement and the contact system, through generation of bradykinin, may play a role in the SARS-CoV-2-induced pulmonary edema, and our search suggests that further work is necessary to confirm our suspicions.
Keywords	covid19
Language	English
Publishing date	2020-05-13
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2364-1746
ISSN (online)	2364-1746
DOI	10.1007/s41030-020-00118-5
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Article ; Online: In vivo deuterium magnetic resonance imaging of xenografted tumors following systemic administration of deuterated water.

Brender, Jeffrey R / Assmann, Julian C / Farthing, Don E / Saito, Keita / Kishimoto, Shun / Warrick, Kathrynne A / Maglakelidze, Natella / Larus, Terri L / Merkle, Hellmut / Gress, Ronald E / Krishna, Murali C / Buxbaum, Nataliya P

Scientific reports

2023 Volume 13, Issue 1, Page(s) 14699

Abstract: In vivo deuterated water ( ...

Abstract	In vivo deuterated water (
MeSH term(s)	Humans ; Animals ; Mice ; Heterografts ; Deuterium ; Magnetic Resonance Imaging ; Transplantation, Heterologous ; Administration, Cutaneous ; Disease Models, Animal ; Neoplasm Seeding
Chemical Substances	Deuterium (AR09D82C7G)
Language	English
Publishing date	2023-09-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-41163-9
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Article ; Online: A Review

Maglakelidze, Natella / Manto, Kristen M. / Craig, Timothy J.

Pulmonary Therapy ; ISSN 2364-1754 2364-1746

Does Complement or the Contact System Have a Role in Protection or Pathogenesis of COVID-19?

2020

Keywords	covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
DOI	10.1007/s41030-020-00118-5
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: A Review: Does Complement or the Contact System Have a Role in Protection or Pathogenesis of COVID-19?

Maglakelidze, Natella / Manto, Kristen M / Craig, Timothy J

Abstract: INTRODUCTION: COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory ... ...

Abstract	INTRODUCTION: COVID-19 presentation may include a profound increase in cytokines and associated pneumonia, rapidly progressing to acute respiratory distress syndrome (ARDS). This so-called cytokine storm often leads to refractory edema, respiratory arrest, and death. At present, anti-IL-6, antiviral therapy, convalescent plasma, hydroxychloroquine, and azithromycin among others are being investigated as potential treatments for COVID-19. As the disease etiology and precise therapeutic interventions are still not definitively defined, we wanted to review the roles that complement and the contact system may have in either the treatment or pathogenesis of the disease. METHODS: We searched the recent literature (PubMed) on complement and coronavirus; contact system and coronavirus; bradykinin and coronavirus; and angiotensin receptor and coronavirus. The manuscript complies with ethics guidelines and was deemed exempt from institutional review board approval according to Human Subjects Protection Office guidelines. RESULTS: Mouse models are available for the study of coronavirus and complement. Although complement is effective in protecting against many viruses, it does not seem to be protective against coronavirus. C3 knockout mice infected with SARS-CoV had less lung disease than wild-type mice, suggesting that complement may play a role in coronavirus pathogenesis. Some evidence suggests that the observed pulmonary edema may be bradykinin-induced and could be the reason that corticosteroids, antihistamines, and other traditional interventions for edema are not effective. Angiotensin-converting enzyme 2 (ACE2) is a co-receptor for SARS-CoV-2, and studies thus far have not concluded a benefit or risk associated with the use of either ACE-inhibitors or angiotensin receptor antagonists. Activation of complement and the contact system, through generation of bradykinin, may play a role in the SARS-CoV-2-induced pulmonary edema, and our search suggests that further work is necessary to confirm our suspicions.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #32405877
Database	COVID19

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Article ; Online: Glycolytic metabolism of pathogenic T cells enables early detection of GVHD by 13C-MRI.

Assmann, Julian C / Farthing, Don E / Saito, Keita / Maglakelidze, Natella / Oliver, Brittany / Warrick, Kathrynne A / Sourbier, Carole / Ricketts, Christopher J / Meyer, Thomas J / Pavletic, Steven Z / Linehan, W Marston / Krishna, Murali C / Gress, Ronald E / Buxbaum, Nataliya P

Blood

2020 Volume 137, Issue 1, Page(s) 126–137

Abstract: Graft-versus-host disease (GVHD) is a prominent barrier to allogeneic hematopoietic stem cell transplantation (AHSCT). Definitive diagnosis of GVHD is invasive, and biopsies of involved tissues pose a high risk of bleeding and infection. T cells are ... ...

Abstract	Graft-versus-host disease (GVHD) is a prominent barrier to allogeneic hematopoietic stem cell transplantation (AHSCT). Definitive diagnosis of GVHD is invasive, and biopsies of involved tissues pose a high risk of bleeding and infection. T cells are central to GVHD pathogenesis, and our previous studies in a chronic GVHD mouse model showed that alloreactive CD4+ T cells traffic to the target organs ahead of overt symptoms. Because increased glycolysis is an early feature of T-cell activation, we hypothesized that in vivo metabolic imaging of glycolysis would allow noninvasive detection of liver GVHD as activated CD4+ T cells traffic into the organ. Indeed, hyperpolarized 13C-pyruvate magnetic resonance imaging detected high rates of conversion of pyruvate to lactate in the liver ahead of animals becoming symptomatic, but not during subsequent overt chronic GVHD. Concomitantly, CD4+ T effector memory cells, the predominant pathogenic CD4+ T-cell subset, were confirmed to be highly glycolytic by transcriptomic, protein, metabolite, and ex vivo metabolic activity analyses. Preliminary data from single-cell sequencing of circulating T cells in patients undergoing AHSCT also suggested that increased glycolysis may be a feature of incipient acute GVHD. Metabolic imaging is being increasingly used in the clinic and may be useful in the post-AHSCT setting for noninvasive early detection of GVHD.
MeSH term(s)	Animals ; CD4-Positive T-Lymphocytes/metabolism ; Carbon Isotopes ; Glycolysis ; Graft vs Host Disease/diagnostic imaging ; Graft vs Host Disease/metabolism ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Lymphocyte Activation/immunology ; Magnetic Resonance Imaging/methods ; Magnetic Resonance Spectroscopy/methods ; Mice ; Single-Cell Analysis/methods ; Transplantation, Homologous
Chemical Substances	Carbon Isotopes ; Carbon-13 (FDJ0A8596D)
Language	English
Publishing date	2020-08-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2020005770
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Article ; Online: Comparing DNA enrichment of proliferating cells following administration of different stable isotopes of heavy water.

Farthing, Don E / Buxbaum, Nataliya P / Lucas, Philip J / Maglakelidze, Natella / Oliver, Brittany / Wang, Jiun / Hu, Kevin / Castro, Ehydel / Bare, Catherine V / Gress, Ronald E

Scientific reports

2017 Volume 7, Issue 1, Page(s) 4043

Abstract: Deuterated water ( ...

Abstract	Deuterated water (
MeSH term(s)	Animals ; Cell Line, Tumor ; Cell Proliferation ; DNA/chemistry ; DNA/genetics ; DNA Replication/drug effects ; Deuterium Oxide/pharmacology ; Isotope Labeling ; Mass Spectrometry ; Mice
Chemical Substances	DNA (9007-49-2) ; Deuterium Oxide (J65BV539M3)
Language	English
Publishing date	2017-06-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-017-04404-2
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Article ; Online: Suppression of p16 Induces mTORC1-Mediated Nucleotide Metabolic Reprogramming.

Buj, Raquel / Chen, Chi-Wei / Dahl, Erika S / Leon, Kelly E / Kuskovsky, Rostislav / Maglakelidze, Natella / Navaratnarajah, Maithili / Zhang, Gao / Doan, Mary T / Jiang, Helen / Zaleski, Michael / Kutzler, Lydia / Lacko, Holly / Lu, Yiling / Mills, Gordon B / Gowda, Raghavendra / Robertson, Gavin P / Warrick, Joshua I / Herlyn, Meenhard /

Imamura, Yuka / Kimball, Scot R / DeGraff, David J / Snyder, Nathaniel W / Aird, Katherine M

Cell reports

2019 Volume 28, Issue 8, Page(s) 1971–1980.e8

Abstract: Reprogrammed metabolism and cell cycle dysregulation are two cancer hallmarks. p16 is a cell cycle inhibitor and tumor suppressor that is upregulated during oncogene-induced senescence (OIS). Loss of p16 allows for uninhibited cell cycle progression, ... ...

Abstract	Reprogrammed metabolism and cell cycle dysregulation are two cancer hallmarks. p16 is a cell cycle inhibitor and tumor suppressor that is upregulated during oncogene-induced senescence (OIS). Loss of p16 allows for uninhibited cell cycle progression, bypass of OIS, and tumorigenesis. Whether p16 loss affects pro-tumorigenic metabolism is unclear. We report that suppression of p16 plays a central role in reprogramming metabolism by increasing nucleotide synthesis. This occurs by activation of mTORC1 signaling, which directly mediates increased translation of the mRNA encoding ribose-5-phosphate isomerase A (RPIA), a pentose phosphate pathway enzyme. p16 loss correlates with activation of the mTORC1-RPIA axis in multiple cancer types. Suppression of RPIA inhibits proliferation only in p16-low cells by inducing senescence both in vitro and in vivo. These data reveal the molecular basis whereby p16 loss modulates pro-tumorigenic metabolism through mTORC1-mediated upregulation of nucleotide synthesis and reveals a metabolic vulnerability of p16-null cancer cells.
MeSH term(s)	Aldose-Ketose Isomerases/metabolism ; Animals ; Cell Line ; Cellular Senescence ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Gene Knockdown Techniques ; Humans ; Male ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice, SCID ; Nucleotides/metabolism ; Pentose Phosphate Pathway ; Protein Biosynthesis
Chemical Substances	Cyclin-Dependent Kinase Inhibitor p16 ; Nucleotides ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Aldose-Ketose Isomerases (EC 5.3.1.-) ; ribosephosphate isomerase (EC 5.3.1.6)
Language	English
Publishing date	2019-08-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2019.07.084
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Article ; Online: Comparing DNA enrichment of proliferating cells following administration of different stable isotopes of heavy water

Don E. Farthing / Nataliya P. Buxbaum / Philip J. Lucas / Natella Maglakelidze / Brittany Oliver / Jiun Wang / Kevin Hu / Ehydel Castro / Catherine V. Bare / Ronald E. Gress

Scientific Reports, Vol 7, Iss 1, Pp 1-

2017 Volume 12

Abstract: Abstract Deuterated water (2H2O) is a label commonly used for safe quantitative measurement of deuterium enrichment into DNA of proliferating cells. More recently, it has been used for labeling proteins and other biomolecules. Our in vitro - in vivo ... ...

Abstract	Abstract Deuterated water (2H2O) is a label commonly used for safe quantitative measurement of deuterium enrichment into DNA of proliferating cells. More recently, it has been used for labeling proteins and other biomolecules. Our in vitro - in vivo research reports important stable isotopic labeling enrichment differences into the DNA nucleosides and their isotopologues (e.g. deoxyadenosine (dA) M + 1, dA M + 2, dA M + 3), as well as tumor cell proliferation effects for various forms of commercially available stable heavy water (2H2O, H2 18O, and 2H2 18O). Using an in vitro mouse thymus tumor cell line, we determined that H2 18O provides superior DNA labeling enrichment quantitation, as measured by GC-positive chemical ionization (PCI)-MS/MS. In addition, at higher but physiologically relevant doses, both 2H2 18O and 2H2O down modulated mouse thymus tumor cell proliferation, whereas H2 18O water had no observable effects on cell proliferation. The in vivo labeling studies, where normal mouse bone marrow cells (i.e. high turnover) were evaluated post labeling, demonstrated DNA enrichments concordant with measurements from the in vitro studies. Our research also reports a headspace-GC-NCI-MS method, which rapidly and quantitatively measures stable heavy water levels in total body water.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2017-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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