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Article ; Online: Lysine Acetylation of Proteins and Its Characterization in Human Systems.

Orren, David K / Machwe, Amrita

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

2019 Volume 1983, Page(s) 107–130

Abstract: Posttranslational acetylation modifications of proteins have important consequences for cell biology, including effects on protein trafficking and cellular localization as well as on the interactions of acetylated proteins with other proteins and ... ...

Abstract	Posttranslational acetylation modifications of proteins have important consequences for cell biology, including effects on protein trafficking and cellular localization as well as on the interactions of acetylated proteins with other proteins and macromolecules such as DNA. Experiments to uncover and characterize protein acetylation events have historically been more challenging than investigating another common posttranslational modification, protein phosphorylation. More recently, high-quality antibodies that recognize acetylated lysine residues present in acetylated proteins and improved proteomic methodologies have facilitated the discovery that acetylation occurs on numerous cellular proteins and allowed characterization of the dynamics and functional effects of many acetylation events. This article summarizes some established biochemical information about how protein acetylation takes place and is regulated, in order to lay the foundation for subsequent descriptions of strategies used by our lab and others either to directly study acetylation of an individual factor or to identify groups of proteins targeted for acetylation that can then be examined in isolation.
MeSH term(s)	Acetylation ; Acetyltransferases/metabolism ; Biological Assay/methods ; Histone Deacetylases/metabolism ; Humans ; Lysine/chemistry ; Lysine/metabolism ; Lysine Acetyltransferases/metabolism ; Protein Processing, Post-Translational ; Proteins/chemistry ; Proteins/metabolism ; Proteome ; Proteomics/methods ; Tandem Mass Spectrometry/methods
Chemical Substances	Proteins ; Proteome ; Acetyltransferases (EC 2.3.1.-) ; Lysine Acetyltransferases (EC 2.3.1.32) ; Histone Deacetylases (EC 3.5.1.98) ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2019-05-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-9434-2_7
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Article ; Online: Hydroxyapatite nanoparticle-modified porous bone grafts with improved cell attachment.

Dhavalikar, Prachi / Jenkins, Dana / Rosen, Natalie / Kannapiran, Aparajith / Salhadar, Karim / Shachaf, Orren / Silverstein, Michael / Cosgriff-Hernández, Elizabeth

Journal of materials chemistry. B

2023 Volume 11, Issue 44, Page(s) 10651–10664

Abstract: Emulsion-templated foams have displayed promise as injectable bone grafts; however, the use of a surfactant as an emulsifier resulted in relatively small pores and impedes cell attachment. Hydroxyapatite nanoparticles were explored as an alternative ... ...

Abstract	Emulsion-templated foams have displayed promise as injectable bone grafts; however, the use of a surfactant as an emulsifier resulted in relatively small pores and impedes cell attachment. Hydroxyapatite nanoparticles were explored as an alternative stabilizer to address these limitations. To this end, hydroxyapatite nanoparticles were first modified with myristic acid to generate the appropriate balance of hydrophobicity to stabilize a water-in-oil emulsion of neopentyl glycol diacrylate and 1,4-butanedithiol.
MeSH term(s)	Humans ; Porosity ; Bone Transplantation ; Emulsions ; Durapatite ; Nanoparticles ; Surface-Active Agents
Chemical Substances	Emulsions ; Durapatite (91D9GV0Z28) ; Surface-Active Agents
Language	English
Publishing date	2023-11-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2702241-9
ISSN	2050-7518 ; 2050-750X
ISSN (online)	2050-7518
ISSN	2050-750X
DOI	10.1039/d3tb01839c
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Article: Screening for complement deficiency.

Orren, A

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

2000 Volume 150, Page(s) 139–158

MeSH term(s)	Blood Coagulation Disorders/blood ; Blood Coagulation Disorders/diagnosis ; Complement Hemolytic Activity Assay/methods ; Complement System Proteins/analysis ; Complement System Proteins/deficiency ; Complement System Proteins/genetics ; DNA/analysis ; DNA/genetics ; Humans ; Immune System Diseases/blood ; Immune System Diseases/diagnosis ; Immunoassay/methods ; Mass Screening/methods ; Properdin/analysis ; Properdin/deficiency
Chemical Substances	Properdin (11016-39-0) ; Complement System Proteins (9007-36-7) ; DNA (9007-49-2)
Language	English
Publishing date	2000
Publishing country	United States
Document type	Journal Article
ISSN	1064-3745
ISSN	1064-3745
DOI	10.1385/1-59259-056-X:139
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Article: Molecular mechanisms of complement component C6 deficiency; a hypervariable exon 6 region responsible for three of six reported defects.

Orren, A

Clinical and experimental immunology

2000 Volume 119, Issue 2, Page(s) 255–258

MeSH term(s)	Complement C6/deficiency ; Complement C6/genetics ; Exons ; Gene Deletion ; Humans
Chemical Substances	Complement C6
Language	English
Publishing date	2000-02
Publishing country	England
Document type	Editorial ; Review
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1046/j.1365-2249.2000.01141.x
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Article ; Online: Strand exchange of telomeric DNA catalyzed by the Werner syndrome protein (WRN) is specifically stimulated by TRF2.

Edwards, Deanna N / Orren, David K / Machwe, Amrita

Nucleic acids research

2014 Volume 42, Issue 12, Page(s) 7748–7761

Abstract: Werner syndrome (WS), caused by loss of function of the RecQ helicase WRN, is a hereditary disease characterized by premature aging and elevated cancer incidence. WRN has DNA binding, exonuclease, ATPase, helicase and strand annealing activities, ... ...

Abstract	Werner syndrome (WS), caused by loss of function of the RecQ helicase WRN, is a hereditary disease characterized by premature aging and elevated cancer incidence. WRN has DNA binding, exonuclease, ATPase, helicase and strand annealing activities, suggesting possible roles in recombination-related processes. Evidence indicates that WRN deficiency causes telomeric abnormalities that likely underlie early onset of aging phenotypes in WS. Furthermore, TRF2, a protein essential for telomere protection, interacts with WRN and influences its basic helicase and exonuclease activities. However, these studies provided little insight into WRN's specific function at telomeres. Here, we explored the possibility that WRN and TRF2 cooperate during telomeric recombination processes. Our results indicate that TRF2, through its interactions with both WRN and telomeric DNA, stimulates WRN-mediated strand exchange specifically between telomeric substrates; TRF2's basic domain is particularly important for this stimulation. Although TRF1 binds telomeric DNA with similar affinity, it has minimal effects on WRN-mediated strand exchange of telomeric DNA. Moreover, TRF2 is displaced from telomeric DNA by WRN, independent of its ATPase and helicase activities. Together, these results suggest that TRF2 and WRN act coordinately during telomeric recombination processes, consistent with certain telomeric abnormalities associated with alteration of WRN function.
MeSH term(s)	Biocatalysis ; DNA/metabolism ; Protein Structure, Tertiary ; RecQ Helicases/metabolism ; Telomere/chemistry ; Telomere/metabolism ; Telomeric Repeat Binding Protein 2/chemistry ; Telomeric Repeat Binding Protein 2/metabolism
Chemical Substances	Telomeric Repeat Binding Protein 2 ; DNA (9007-49-2) ; RecQ Helicases (EC 3.6.4.12)
Language	English
Publishing date	2014-05-31
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gku454
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Article ; Online: Complement factor 5 (C5) p.A252T mutation is prevalent in, but not restricted to, sub-Saharan Africa: implications for the susceptibility to meningococcal disease.

Franco-Jarava, C / Comas, D / Orren, A / Hernández-González, M / Colobran, R

Clinical and experimental immunology

2017 Volume 189, Issue 2, Page(s) 226–231

Abstract: Complement C5 deficiency (C5D) is a rare primary immunodeficiency associated with recurrent infections, particularly meningitis, by Neisseria species. To date, studies to elucidate the molecular basis of hereditary C5D have included fewer than 40 ... ...

Abstract	Complement C5 deficiency (C5D) is a rare primary immunodeficiency associated with recurrent infections, particularly meningitis, by Neisseria species. To date, studies to elucidate the molecular basis of hereditary C5D have included fewer than 40 families, and most C5 mutations (13 of 17) have been found in single families. However, the recently described C5 p.A252T mutation is reported to be associated with approximately 7% of meningococcal disease cases in South Africa. This finding raises the question of whether the mutation may be prevalent in other parts of Africa or other continental regions. The aim of this study was to investigate the prevalence of C5 p.A252T in Africa and other regions and discuss the implications for prophylaxis against meningococcal disease. In total, 2710 samples from healthy donors within various populations worldwide were analysed by quantitative polymerase chain reaction (qPCR) assay to detect the C5 p.A252T mutation. Eleven samples were found to be heterozygous for p.A252T, and nine of these samples were from sub-Saharan African populations (allele frequency 0·94%). Interestingly, two other heterozygous samples were from individuals in populations outside Africa (Israel and Pakistan). These findings, together with data from genomic variation databases, indicate a 0·5-2% prevalence of the C5 p.A252T mutation in heterozygosity in sub-Saharan Africa. Therefore, this mutation may have a relevant role in meningococcal disease susceptibility in this geographical area.
MeSH term(s)	African Continental Ancestry Group/genetics ; Complement C5/deficiency ; Complement C5/genetics ; Disease Susceptibility ; Gene Frequency ; Heterozygote ; Humans ; Immunologic Deficiency Syndromes/epidemiology ; Immunologic Deficiency Syndromes/genetics ; Mass Screening ; Meningitis, Meningococcal/genetics ; Mutation ; South Africa
Chemical Substances	Complement C5
Language	English
Publishing date	2017-04-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1111/cei.12967
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Article ; Online: Adding four-dimensional data assimilation by analysis nudging to the Model for Prediction Across Scales - Atmosphere (version 4.0).

Bullock, Orren Russell / Foroutan, Hosein / Gilliam, Robert C / Herwehe, Jerold A

Geoscientific model development

2019 Volume 11, Page(s) 2897–2922

Abstract: The Model for Prediction Across Scales - Atmosphere (MPAS-A) has been modified to allow four-dimensional data assimilation (FDDA) by the nudging of temperature, humidity, and wind toward target values predefined on the MPAS-A computational mesh. The ... ...

Abstract	The Model for Prediction Across Scales - Atmosphere (MPAS-A) has been modified to allow four-dimensional data assimilation (FDDA) by the nudging of temperature, humidity, and wind toward target values predefined on the MPAS-A computational mesh. The addition of nudging allows MPAS-A to be used as a global-scale meteorological driver for retrospective air quality modeling. The technique of "analysis nudging" developed for the Penn State/National Center for Atmospheric Research (NCAR) Mesoscale Model, and later applied in the Weather Research and Forecasting model, is implemented in MPAS-A with adaptations for its polygonal Voronoi mesh. Reference fields generated from 1°×1° National Centers for Environmental Prediction (NCEP) FNL (Final) Operational Global Analysis data were used to constrain MPAS-A simulations on a 92-25km variable-resolution mesh with refinement centered over the contiguous United States. Test simulations were conducted for January and July 2013 with and without FDDA, and compared to reference fields and near-surface meteorological observations. The results demonstrate that MPAS-A with analysis nudging has high fidelity to the reference data while still maintaining conservation of mass as in the unmodified model. The results also show that application of FDDA constrains model errors relative to 2m temperature, 2m water vapor mixing ratio, and 10m wind speed such that they continue to be at or below the magnitudes found at the start of each test period.
Language	English
Publishing date	2019-04-09
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2456725-5
ISSN	1991-9603 ; 1991-959X
ISSN (online)	1991-9603
ISSN	1991-959X
DOI	10.5194/gmd-11-2897-2018
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Article ; Online: Plasma Nitric Oxide Consumption Is Elevated and Associated With Adverse Outcomes in Critically Ill Patients.

Dony, Christina A / Illipparambil, Lijo C / Maeda, Tetsuro / Mroczek, Susan K / Rovitelli, Amy / Wexler, Orren / Malnoske, Michelle / Bice, Tristan / Fe, Alex Z / Storms, Casey R / Zhang, Jimmy / Schultz, Rebecca D / Pietropaoli, Anthony P

Critical care medicine

2023 Volume 51, Issue 12, Page(s) 1706–1715

Abstract: Objectives: Impaired nitric oxide (NO) bioavailability may contribute to microvascular dysfunction in sepsis. Excessive plasma NO consumption has been attributed to scavenging by circulating cell-free hemoglobin. This may be a mechanism for NO ... ...

Abstract	Objectives: Impaired nitric oxide (NO) bioavailability may contribute to microvascular dysfunction in sepsis. Excessive plasma NO consumption has been attributed to scavenging by circulating cell-free hemoglobin. This may be a mechanism for NO deficiency in sepsis and critical illness. We hypothesized that plasma NO consumption is high in critically ill patients, particularly those with sepsis, acute respiratory distress syndrome (ARDS), shock, and in hospital nonsurvivors. We further hypothesized that plasma NO consumption is correlated with plasma cell-free hemoglobin concentration. Design: Retrospective cohort study. Setting: Adult ICUs of an academic medical center. Patients and subjects: Three hundred sixty-two critically ill patients and 46 healthy control subjects. Interventions: None. Measurements and main results: Plasma NO consumption was measured using reductive chemiluminescence and cell-free hemoglobin was measured with a colorimetric assay. Mean (95% CI) plasma NO consumption (µM) was higher in critically ill patients versus healthy control subjects (3.9 [3.7-4.1] vs 2.1 [1.8-2.5]), septic versus nonseptic patients (4.1 [3.8-4.3] vs 3.6 [3.3-3.8]), ARDS versus non-ARDS patients (4.4 [4.0-4.9] vs 3.7 [3.6-3.9]), shock vs nonshock patients (4.4 [4.0-4.8] vs 3.6 [3.4-3.8]), and hospital nonsurvivors versus survivors (5.3 [4.4-6.4] vs 3.7 [3.6-3.9]). These relationships remained significant in multivariable analyses. Plasma cell-free hemoglobin was weakly correlated with plasma NO consumption. Conclusions: Plasma NO consumption is elevated in critically ill patients and independently associated with sepsis, ARDS, shock, and hospital death. These data suggest that excessive intravascular NO scavenging characterizes sepsis and adverse outcomes of critical illness.
MeSH term(s)	Adult ; Humans ; Critical Illness ; Nitric Oxide ; Retrospective Studies ; Sepsis ; Hemoglobins ; Respiratory Distress Syndrome
Chemical Substances	Nitric Oxide (31C4KY9ESH) ; Hemoglobins
Language	English
Publishing date	2023-08-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	197890-1
ISSN	1530-0293 ; 0090-3493
ISSN (online)	1530-0293
ISSN	0090-3493
DOI	10.1097/CCM.0000000000006006
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Article ; Online: Inferring light responses of primate retinal ganglion cells using intrinsic electrical signatures.

Zaidi, Moosa / Aggarwal, Gorish / Shah, Nishal P / Karniol-Tambour, Orren / Goetz, Georges / Madugula, Sasidhar S / Gogliettino, Alex R / Wu, Eric G / Kling, Alexandra / Brackbill, Nora / Sher, Alexander / Litke, Alan M / Chichilnisky, E J

Journal of neural engineering

2023 Volume 20, Issue 4

Abstract: ... ...

Abstract	Objective
MeSH term(s)	Animals ; Retinal Ganglion Cells/physiology ; Action Potentials/physiology ; Electric Stimulation/methods ; Retina/physiology ; Retinal Degeneration ; Macaca
Language	English
Publishing date	2023-08-31
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2170901-4
ISSN	1741-2552 ; 1741-2560
ISSN (online)	1741-2552
ISSN	1741-2560
DOI	10.1088/1741-2552/ace657
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Article: How do mammals distinguish between pathogens and non-self?

Orren, A

Trends in microbiology

1996 Volume 4, Issue 7, Page(s) 254–257

MeSH term(s)	Animals ; Chickens ; Complement C3/deficiency ; Complement Pathway, Alternative/drug effects ; Complement Pathway, Alternative/immunology ; Humans ; Membrane Proteins/metabolism ; Mice ; N-Acetylneuraminic Acid/pharmacology ; Polysaccharides, Bacterial/immunology ; Polysaccharides, Bacterial/metabolism ; Virulence
Chemical Substances	Complement C3 ; Membrane Proteins ; Polysaccharides, Bacterial ; N-Acetylneuraminic Acid (GZP2782OP0)
Language	English
Publishing date	1996-07
Publishing country	England
Document type	Journal Article
ZDB-ID	1158963-2
ISSN	1878-4380 ; 0966-842X
ISSN (online)	1878-4380
ISSN	0966-842X
DOI	10.1016/0966-842x(96)30019-x
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