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Article ; Online: Microbiology: The bacterial cell wall takes centre stage.

Young, Kevin D

2016 Volume 537, Issue 7622, Page(s) 622–624

MeSH term(s)	Cell Wall ; Microbiology ; Models, Biological
Language	English
Publishing date	2016--29
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/537622a
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Article ; Online: Individualized Treatment Effects of Oxygen Targets in Mechanically Ventilated Critically Ill Adults.

Buell, Kevin G / Spicer, Alexandra B / Casey, Jonathan D / Seitz, Kevin P / Qian, Edward T / Graham Linck, Emma J / Self, Wesley H / Rice, Todd W / Sinha, Pratik / Young, Paul J / Semler, Matthew W / Churpek, Matthew M

JAMA

2024 Volume 331, Issue 14, Page(s) 1195–1204

Abstract: Importance: Among critically ill adults, randomized trials have not found oxygenation targets to affect outcomes overall. Whether the effects of oxygenation targets differ based on an individual's characteristics is unknown.: Objective: To determine ... ...

Abstract	Importance: Among critically ill adults, randomized trials have not found oxygenation targets to affect outcomes overall. Whether the effects of oxygenation targets differ based on an individual's characteristics is unknown. Objective: To determine whether an individual's characteristics modify the effect of lower vs higher peripheral oxygenation-saturation (Spo2) targets on mortality. Design, setting, and participants: A machine learning model to predict the effect of treatment with a lower vs higher Spo2 target on mortality for individual patients was derived in the Pragmatic Investigation of Optimal Oxygen Targets (PILOT) trial and externally validated in the Intensive Care Unit Randomized Trial Comparing Two Approaches to Oxygen Therapy (ICU-ROX) trial. Critically ill adults received invasive mechanical ventilation in an intensive care unit (ICU) in the United States between July 2018 and August 2021 for PILOT (n = 1682) and in 21 ICUs in Australia and New Zealand between September 2015 and May 2018 for ICU-ROX (n = 965). Exposures: Randomization to a lower vs higher Spo2 target group. Main outcome and measure: 28-Day mortality. Results: In the ICU-ROX validation cohort, the predicted effect of treatment with a lower vs higher Spo2 target for individual patients ranged from a 27.2% absolute reduction to a 34.4% absolute increase in 28-day mortality. For example, patients predicted to benefit from a lower Spo2 target had a higher prevalence of acute brain injury, whereas patients predicted to benefit from a higher Spo2 target had a higher prevalence of sepsis and abnormally elevated vital signs. Patients predicted to benefit from a lower Spo2 target experienced lower mortality when randomized to the lower Spo2 group, whereas patients predicted to benefit from a higher Spo2 target experienced lower mortality when randomized to the higher Spo2 group (likelihood ratio test for effect modification P = .02). The use of a Spo2 target predicted to be best for each patient, instead of the randomized Spo2 target, would have reduced the absolute overall mortality by 6.4% (95% CI, 1.9%-10.9%). Conclusion and relevance: Oxygenation targets that are individualized using machine learning analyses of randomized trials may reduce mortality for critically ill adults. A prospective trial evaluating the use of individualized oxygenation targets is needed.
MeSH term(s)	Adult ; Humans ; Oxygen/therapeutic use ; Critical Illness/therapy ; Respiration, Artificial ; Prospective Studies ; Oxygen Inhalation Therapy ; Intensive Care Units
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2024-04-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2958-0
ISSN	1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
ISSN (online)	1538-3598
ISSN	0254-9077 ; 0002-9955 ; 0098-7484
DOI	10.1001/jama.2024.2933
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Article ; Online: Unwrapping bacteria.

Young, Kevin D

PLoS genetics

2014 Volume 10, Issue 1, Page(s) e1004054

MeSH term(s)	Cell Membrane/genetics ; Cell Wall/genetics ; Escherichia coli/genetics
Language	English
Publishing date	2014-01-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1004054
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Article ; Online: Photolysis of Dissolved Organic Matter over Hematite Nanoplatelets.

Huang, Xiaopeng / Song, Duo / Zhao, Qian / Young, Robert P / Chen, Ying / Walter, Eric D / Lahiri, Nabajit / Taylor, Sandra D / Wang, Zheming / Hofmockel, Kirsten S / Rosario-Ortiz, Fernando / Lowry, Gregory V / Rosso, Kevin M

Environmental science & technology

2024 Volume 58, Issue 6, Page(s) 2798–2807

Abstract: Solar photoexcitation of chromophoric groups in dissolved organic matter (DOM), when coupled to photoreduction of ubiquitous Fe(III)-oxide nanoparticles, can significantly accelerate DOM degradation in near-surface terrestrial systems, but the mechanisms ...

Abstract	Solar photoexcitation of chromophoric groups in dissolved organic matter (DOM), when coupled to photoreduction of ubiquitous Fe(III)-oxide nanoparticles, can significantly accelerate DOM degradation in near-surface terrestrial systems, but the mechanisms of these reactions remain elusive. We examined the photolysis of chromophoric soil DOM coated onto hematite nanoplatelets featuring (001) exposed facets using a combination of molecular spectroscopies and density functional theory (DFT) computations. Reactive oxygen species (ROS) probed by electron paramagnetic resonance (EPR) spectroscopy revealed that both singlet oxygen and superoxide are the predominant ROS responsible for DOM degradation. DFT calculations confirmed that Fe(II) on the hematite (001) surface, created by interfacial electron transfer from photoexcited chromophores in DOM, can reduce dioxygen molecules to superoxide radicals (
MeSH term(s)	Reactive Oxygen Species ; Dissolved Organic Matter ; Ferric Compounds ; Superoxides ; Photolysis
Chemical Substances	Reactive Oxygen Species ; Dissolved Organic Matter ; ferric oxide (1K09F3G675) ; Ferric Compounds ; Superoxides (11062-77-4)
Language	English
Publishing date	2024-01-31
Publishing country	United States
Document type	Journal Article
ISSN	1520-5851
ISSN (online)	1520-5851
DOI	10.1021/acs.est.3c08752
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Article ; Online: Streptomyces umbrella toxin particles block hyphal growth of competing species.

Zhao, Qinqin / Bertolli, Savannah / Park, Young-Jun / Tan, Yongjun / Cutler, Kevin J / Srinivas, Pooja / Asfahl, Kyle L / Fonesca-García, Citlali / Gallagher, Larry A / Li, Yaqiao / Wang, Yaxi / Coleman-Derr, Devin / DiMaio, Frank / Zhang, Dapeng / Peterson, S Brook / Veesler, David / Mougous, Joseph D

Nature

2024

Abstract: Streptomyces are a genus of ubiquitous soil bacteria from which the majority of clinically utilized antibiotics ... ...

Abstract	Streptomyces are a genus of ubiquitous soil bacteria from which the majority of clinically utilized antibiotics derive
Language	English
Publishing date	2024-04-17
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-024-07298-z
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Sugar-Phosphate Metabolism Regulates Stationary-Phase Entry and Stalk Elongation in Caulobacter crescentus.

de Young, Kevin D / Stankeviciute, Gabriele / Klein, Eric A

Journal of bacteriology

2020 Volume 202, Issue 4

Abstract: Bacteria have a variety of mechanisms for adapting to environmental perturbations. Changes in oxygen availability result in a switch between aerobic and anaerobic respiration, whereas iron limitation may lead to siderophore secretion. In addition to ... ...

Abstract	Bacteria have a variety of mechanisms for adapting to environmental perturbations. Changes in oxygen availability result in a switch between aerobic and anaerobic respiration, whereas iron limitation may lead to siderophore secretion. In addition to metabolic adaptations, many organisms respond by altering their cell shape.
MeSH term(s)	Caulobacter crescentus/genetics ; Caulobacter crescentus/growth & development ; Caulobacter crescentus/metabolism ; Mannose-6-Phosphate Isomerase/genetics ; Mannose-6-Phosphate Isomerase/physiology ; Metabolic Networks and Pathways ; Mutation ; Phosphates/metabolism ; Polymorphism, Single Nucleotide ; Sugars/metabolism
Chemical Substances	Phosphates ; Sugars ; Mannose-6-Phosphate Isomerase (EC 5.3.1.8)
Language	English
Publishing date	2020-01-29
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/JB.00468-19
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Article ; Online: Overexpression of peroxisome proliferator-activated receptor γ co-activator-1⍺ (PGC-1⍺) in Chinese hamster ovary cells increases oxidative metabolism and IgG productivity.

Sacco, Sarah A / McAtee Pereira, Allison G / Trenary, Irina / Smith, Kevin D / Betenbaugh, Michael J / Young, Jamey D

Metabolic engineering

2023 Volume 79, Page(s) 108–117

Abstract: Chinese hamster ovary (CHO) cells are used extensively to produce protein therapeutics, such as monoclonal antibodies (mAbs), in the biopharmaceutical industry. MAbs are large proteins that are energetically demanding to synthesize and secrete; therefore, ...

Abstract	Chinese hamster ovary (CHO) cells are used extensively to produce protein therapeutics, such as monoclonal antibodies (mAbs), in the biopharmaceutical industry. MAbs are large proteins that are energetically demanding to synthesize and secrete; therefore, high-producing CHO cell lines that are engineered for maximum metabolic efficiency are needed to meet increasing demands for mAb production. Previous studies have identified that high-producing cell lines possess a distinct metabolic phenotype when compared to low-producing cell lines. In particular, it was found that high mAb production is correlated to lactate consumption and elevated TCA cycle flux. We hypothesized that enhancing flux through the mitochondrial TCA cycle and oxidative phosphorylation would lead to increased mAb productivities and final titers. To test this hypothesis, we overexpressed peroxisome proliferator-activated receptor γ co-activator-1⍺ (PGC-1⍺), a gene that promotes mitochondrial metabolism, in an IgG-producing parental CHO cell line. Stable cell pools overexpressing PGC-1⍺ exhibited increased oxygen consumption, indicating increased mitochondrial metabolism, as well as increased mAb specific productivity compared to the parental line. We also performed
MeSH term(s)	Cricetinae ; Animals ; Cricetulus ; CHO Cells ; PPAR gamma/metabolism ; Antibodies, Monoclonal/genetics ; Oxidative Stress ; Immunoglobulin G
Chemical Substances	PPAR gamma ; Antibodies, Monoclonal ; Immunoglobulin G
Language	English
Publishing date	2023-07-18
Publishing country	Belgium
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1470383-x
ISSN	1096-7184 ; 1096-7176
ISSN (online)	1096-7184
ISSN	1096-7176
DOI	10.1016/j.ymben.2023.07.005
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Article ; Online: Microbiology. A flipping cell wall ferry.

Young, Kevin D

Science (New York, N.Y.)

2014 Volume 345, Issue 6193, Page(s) 139–140

MeSH term(s)	Cell Wall/metabolism ; Escherichia coli/metabolism ; Escherichia coli Proteins/physiology ; Peptidoglycan/biosynthesis ; Phospholipid Transfer Proteins/physiology ; Uridine Diphosphate N-Acetylmuramic Acid/analogs & derivatives ; Uridine Diphosphate N-Acetylmuramic Acid/metabolism
Chemical Substances	Escherichia coli Proteins ; MurJ protein, E coli ; Peptidoglycan ; Phospholipid Transfer Proteins ; Uridine Diphosphate N-Acetylmuramic Acid ; muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol
Language	English
Publishing date	2014-07-10
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.1256585
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Article ; Online: YtfB, an OapA Domain-Containing Protein, Is a New Cell Division Protein in Escherichia coli.

Jorgenson, Matthew A / Young, Kevin D

Journal of bacteriology

2018 Volume 200, Issue 13

Abstract: While screening the Pfam database for novel peptidoglycan (PG) binding modules, we identified the OapA domain, which is annotated as a LysM-like domain. LysM domains bind PG and mediate localization to the septal ring. In the Gram-negative ... ...

Abstract	While screening the Pfam database for novel peptidoglycan (PG) binding modules, we identified the OapA domain, which is annotated as a LysM-like domain. LysM domains bind PG and mediate localization to the septal ring. In the Gram-negative bacterium
MeSH term(s)	Cell Cycle Proteins/chemistry ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cell Division ; Cell Wall/genetics ; Cell Wall/metabolism ; Escherichia coli/chemistry ; Escherichia coli/cytology ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Escherichia coli Proteins/chemistry ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Peptidoglycan/metabolism ; Protein Domains
Chemical Substances	Cell Cycle Proteins ; Escherichia coli Proteins ; Peptidoglycan ; YtfB protein, E coli
Language	English
Publishing date	2018-06-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2968-3
ISSN	1098-5530 ; 0021-9193
ISSN (online)	1098-5530
ISSN	0021-9193
DOI	10.1128/JB.00046-18
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Article ; Online: MYC overrides HIF-1α to regulate proliferating primary cell metabolism in hypoxia.

Copeland, Courtney A / Olenchock, Benjamin A / Ziehr, David / McGarrity, Sarah / Leahy, Kevin / Young, Jamey D / Loscalzo, Joseph / Oldham, William M

eLife

2023 Volume 12

Abstract: Hypoxia requires metabolic adaptations to sustain energetically demanding cellular activities. While the metabolic consequences of hypoxia have been studied extensively in cancer cell models, comparatively little is known about how primary cell ... ...

Abstract	Hypoxia requires metabolic adaptations to sustain energetically demanding cellular activities. While the metabolic consequences of hypoxia have been studied extensively in cancer cell models, comparatively little is known about how primary cell metabolism responds to hypoxia. Thus, we developed metabolic flux models for human lung fibroblast and pulmonary artery smooth muscle cells proliferating in hypoxia. Unexpectedly, we found that hypoxia decreased glycolysis despite activation of hypoxia-inducible factor 1α (HIF-1α) and increased glycolytic enzyme expression. While HIF-1α activation in normoxia by prolyl hydroxylase (PHD) inhibition did increase glycolysis, hypoxia blocked this effect. Multi-omic profiling revealed distinct molecular responses to hypoxia and PHD inhibition, and suggested a critical role for MYC in modulating HIF-1α responses to hypoxia. Consistent with this hypothesis, MYC knockdown in hypoxia increased glycolysis and MYC over-expression in normoxia decreased glycolysis stimulated by PHD inhibition. These data suggest that MYC signaling in hypoxia uncouples an increase in HIF-dependent glycolytic gene transcription from glycolytic flux.
MeSH term(s)	Humans ; Cell Hypoxia ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit ; Lung ; Procollagen-Proline Dioxygenase ; Proto-Oncogene Proteins c-myc/genetics ; Signal Transduction
Chemical Substances	Hypoxia-Inducible Factor 1, alpha Subunit ; Procollagen-Proline Dioxygenase (EC 1.14.11.2) ; Proto-Oncogene Proteins c-myc ; HIF1A protein, human ; MYC protein, human
Language	English
Publishing date	2023-07-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.82597
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