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Article ; Online: Fitm2 is required for ER homeostasis and normal function of murine liver.

Bond, Laura M / Ibrahim, Ayon / Lai, Zon W / Walzem, Rosemary L / Bronson, Roderick T / Ilkayeva, Olga R / Walther, Tobias C / Farese, Robert V

The Journal of biological chemistry

2023 Volume 299, Issue 3, Page(s) 103022

Abstract: The endoplasmic reticulum (ER)-resident protein fat storage-inducing transmembrane protein 2 (FIT2) catalyzes acyl-CoA cleavage in vitro and is required for ER homeostasis and normal lipid storage in cells. The gene encoding FIT2 is essential for the ... ...

Abstract	The endoplasmic reticulum (ER)-resident protein fat storage-inducing transmembrane protein 2 (FIT2) catalyzes acyl-CoA cleavage in vitro and is required for ER homeostasis and normal lipid storage in cells. The gene encoding FIT2 is essential for the viability of mice and worms. Whether FIT2 acts as an acyl-CoA diphosphatase in vivo and how this activity affects the liver, where the protein was discovered, are unknown. Here, we report that hepatocyte-specific Fitm2 knockout (FIT2-LKO) mice fed a chow diet exhibited elevated acyl-CoA levels, ER stress, and signs of liver injury. These mice also had more triglycerides in their livers than control littermates due, in part, to impaired secretion of triglyceride-rich lipoproteins and reduced capacity for fatty acid oxidation. We found that challenging FIT2-LKO mice with a high-fat diet worsened hepatic ER stress and liver injury but unexpectedly reversed the steatosis phenotype, similar to what is observed in FIT2-deficient cells loaded with fatty acids. Our findings support the model that FIT2 acts as an acyl-CoA diphosphatase in vivo and is crucial for normal hepatocyte function and ER homeostasis in the murine liver.
MeSH term(s)	Animals ; Mice ; Liver/metabolism ; Triglycerides/metabolism ; Fatty Liver/metabolism ; Hepatocytes/metabolism ; Endoplasmic Reticulum/metabolism ; Mice, Knockout ; Homeostasis ; Membrane Proteins/metabolism
Chemical Substances	Triglycerides ; FIT2 protein, mouse ; Membrane Proteins
Language	English
Publishing date	2023-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2023.103022
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Article ; Online: Persistence of a Skewed Repertoire of NK Cells in People with HIV-1 on Long-Term Antiretroviral Therapy.

Anderko, Renee R / DePuyt, Allison E / Bronson, Rhianna / Bullotta, Arlene C / Aga, Evgenia / Bosch, Ronald J / Jones, R Brad / Eron, Joseph J / Mellors, John W / Gandhi, Rajesh T / McMahon, Deborah K / Macatangay, Bernard J / Rinaldo, Charles R / Mailliard, Robbie B

Journal of immunology (Baltimore, Md. : 1950)

2024

Abstract: HIV-1 infection greatly alters the NK cell phenotypic and functional repertoire. This is highlighted by the expansion of a rare population of FcRγ- NK cells exhibiting characteristics of traditional immunologic memory in people with HIV (PWH). Although ... ...

Abstract	HIV-1 infection greatly alters the NK cell phenotypic and functional repertoire. This is highlighted by the expansion of a rare population of FcRγ- NK cells exhibiting characteristics of traditional immunologic memory in people with HIV (PWH). Although current antiretroviral therapy (ART) effectively controls HIV-1 viremia and disease progression, its impact on HIV-1-associated NK cell abnormalities remains unclear. To address this, we performed a longitudinal analysis detailing conventional and memory-like NK cell characteristics in n = 60 PWH during the first 4 y of ART. Throughout this regimen, a skewed repertoire of cytokine unresponsive FcRγ- memory-like NK cells persisted and accompanied an overall increase in NK surface expression of CD57 and KLRG1, suggestive of progression toward immune senescence. These traits were linked to elevated serum inflammatory biomarkers and increasing Ab titers to human CMV, with human CMV viremia detected in approximately one-third of PWH at years 1-4 of ART. Interestingly, 40% of PWH displayed atypical NK cell subsets, representing intermediate stages of NK-poiesis based on single-cell multiomic trajectory analysis. Our findings indicate that NK cell irregularities persist in PWH despite long-term ART, underscoring the need to better understand the causative mechanisms that prevent full restoration of immune health in PWH.
Language	English
Publishing date	2024-03-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2300672
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Article: Preoperative Pain Catastrophizing and Neuropathic Pain Do Not Predict Length of Stay and Early Post-Operative Complications following Total Joint Arthroplasty.

Shemesh, Shai S / Dieterich, James Douglas / Chen, Darwin / Sharon, Roni / Bronson, Michael J / Frenkel Rutenberg, Tal / Moucha, Calin S

Journal of personalized medicine

2023 Volume 13, Issue 2

Abstract: Background: Both pain catastrophizing and neuropathic pain have been suggested as prospective risk factors for poor postoperative pain outcomes in total joint arthroplasty (TJA).: Objective: We hypothesized that pain catastrophizers, as well as ... ...

Abstract	Background: Both pain catastrophizing and neuropathic pain have been suggested as prospective risk factors for poor postoperative pain outcomes in total joint arthroplasty (TJA). Objective: We hypothesized that pain catastrophizers, as well as patients with pain characterized as neuropathic, would exhibit higher pain scores, higher early complication rates and longer lengths of stay following primary TJA. Methods: A prospective, observational study in a single academic institution included 100 patients with end-stage hip or knee osteoarthritis scheduled for TJA. In pre-surgery, measures of health status, socio-demographics, opioid use, neuropathic pain (PainDETECT), pain catastrophizing (PCS), pain at rest and pain during activity (WOMAC pain items) were collected. The primary outcome measure was the length of stay (LOS) and secondary measures were the discharge destinations, early postoperative complications, readmissions, visual analog scale (VAS) levels and distances walked during the hospital stay. Results: The prevalence of pain catastrophizing (PCS ≥ 30) and neuropathic pain (PainDETECT ≥ 19) was 45% and 20.4%, respectively. Preoperative PCS correlated positively with PainDETECT (rs = 0.501, Conclusions: Both PCS and PainDETECT were found to be poor predictors of postoperative pain, LOS and other immediate postoperative outcomes following TJA.
Language	English
Publishing date	2023-01-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm13020216
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Article ; Online: Cellular Mechanisms of Cortisol-Induced Changes in Mauthner-Cell Excitability in the Startle Circuit of Goldfish.

Bronson, Daniel R / Preuss, Thomas

Frontiers in neural circuits

2017 Volume 11, Page(s) 68

Abstract: Predator pressure and olfactory cues (alarm substance) have been shown to modulate Mauthner cell (M-cell) initiated startle escape responses (C-starts) in teleost fish. The regulation of such adaptive responses to potential threats is thought to involve ... ...

Abstract	Predator pressure and olfactory cues (alarm substance) have been shown to modulate Mauthner cell (M-cell) initiated startle escape responses (C-starts) in teleost fish. The regulation of such adaptive responses to potential threats is thought to involve the release of steroid hormones such as cortisol. However, the mechanism by which cortisol may regulate M-cell excitability is not known. Here, we used intrasomatic,
MeSH term(s)	Acoustic Stimulation ; Animals ; Auditory Perception/physiology ; Feedback, Physiological/physiology ; Goldfish ; Hydrocortisone/metabolism ; Membrane Potentials/physiology ; Microelectrodes ; Neural Inhibition/physiology ; Neural Pathways/cytology ; Neural Pathways/metabolism ; Neurons/cytology ; Neurons/metabolism ; Reflex, Startle/physiology
Chemical Substances	Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2017
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2452968-0
ISSN	1662-5110 ; 1662-5110
ISSN (online)	1662-5110
ISSN	1662-5110
DOI	10.3389/fncir.2017.00068
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Article: Fusarioid community diversity associated with conifer seedlings in forest nurseries across the contiguous USA.

Dobbs, J T / Kim, M-S / Reynolds, G J / Wilhelmi, N / Dumroese, R K / Klopfenstein, N B / Fraedrich, S W / Cram, M M / Bronson, J / Stewart, J E

Frontiers in plant science

2023 Volume 14, Page(s) 1104675

Abstract: Introduction: Fusarioid fungi that cause damping-off and root diseases can result in significant losses to conifer crops produced in forest nurseries across the USA. These nurseries are vital to reforestation and forest restoration efforts. ... ...

Abstract	Introduction: Fusarioid fungi that cause damping-off and root diseases can result in significant losses to conifer crops produced in forest nurseries across the USA. These nurseries are vital to reforestation and forest restoration efforts. Understanding the diversity of Fusarioid fungi associated with damping-off and root diseases of conifer seedlings can provide an approach for targeted management techniques to limit seedling losses and pathogen spread to novel landscapes. Methods: This study identifies 26 Results: Phylogenetic analyses identified Fusarioid fungi haplotypes that were associated with 1) host specificity, 2) localization to geographic regions, or 3) generalists found on multiple hosts across diverse geographic regions. Discussion: The haplotypes and novel species identified on conifer seedlings should be considered for further analysis to determine pathogenicity, pathogen spread, and assess management practices.
Language	English
Publishing date	2023-01-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2613694-6
ISSN	1664-462X
ISSN	1664-462X
DOI	10.3389/fpls.2023.1104675
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Article ; Online: Computational Construction of Toxicant Signaling Networks.

Law, Jeffrey N / Orbach, Sophia M / Weston, Bronson R / Steele, Peter A / Rajagopalan, Padmavathy / Murali, T M

Chemical research in toxicology

2023 Volume 36, Issue 8, Page(s) 1267–1277

Abstract: Humans and animals are regularly exposed to compounds that may have adverse effects on health. The Toxicity Forecaster (ToxCast) program was developed to use high throughput screening assays to quickly screen chemicals by measuring their effects on many ... ...

Abstract	Humans and animals are regularly exposed to compounds that may have adverse effects on health. The Toxicity Forecaster (ToxCast) program was developed to use high throughput screening assays to quickly screen chemicals by measuring their effects on many biological end points. Many of these assays test for effects on cellular receptors and transcription factors (TFs), under the assumption that a toxicant may perturb normal signaling pathways in the cell. We hypothesized that we could reconstruct the intermediate proteins in these pathways that may be directly or indirectly affected by the toxicant, potentially revealing important physiological processes not yet tested for many chemicals. We integrate data from ToxCast with a human protein interactome to build toxicant signaling networks that contain physical and signaling protein interactions that may be affected as a result of toxicant exposure. To build these networks, we developed the EdgeLinker algorithm, which efficiently finds short paths in the interactome that connect the receptors to TFs for each toxicant. We performed multiple evaluations and found evidence suggesting that these signaling networks capture biologically relevant effects of toxicants. To aid in dissemination and interpretation, interactive visualizations of these networks are available at http://graphspace.org.
MeSH term(s)	Animals ; Humans ; High-Throughput Screening Assays ; Algorithms ; Signal Transduction ; Drug-Related Side Effects and Adverse Reactions
Language	English
Publishing date	2023-07-20
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	639353-6
ISSN	1520-5010 ; 0893-228X
ISSN (online)	1520-5010
ISSN	0893-228X
DOI	10.1021/acs.chemrestox.2c00422
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Article ; Online: Temporal Artery Biopsy: When Is It Worth the Headache?

Bomkamp, Bronson T / Borgert, Andrew J / Fitzsimmons, Alec J / Smith, Travis J / Shakhnovich, Irina / Peschman, Jacob R

WMJ : official publication of the State Medical Society of Wisconsin

2023 Volume 122, Issue 1, Page(s) 38–43

Abstract: Background: Temporal artery biopsy is ordered when clinical symptoms and an elevated C-reactive protein values and/or erythrocyte sedimentation rates suggest giant cell arteritis. The percentage of temporal artery biopsies positive for giant cell ... ...

Abstract	Background: Temporal artery biopsy is ordered when clinical symptoms and an elevated C-reactive protein values and/or erythrocyte sedimentation rates suggest giant cell arteritis. The percentage of temporal artery biopsies positive for giant cell arteritis is low. The objectives of our study were to analyze the diagnostic yield of temporal artery biopsies at an independent academic medical center and to develop a risk stratification model for triaging patients for possible temporal artery biopsy. Methods: We retrospectively reviewed the electronic health records of all patients who underwent temporal artery biopsy in our institution from January 2010 through February 2020. We compared clinical symptoms and inflammatory marker (C-reactive protein and erythrocyte sedimentation rate) values of patients whose specimens were positive for giant cell arteritis with those of patients with negative specimens. Statistical analysis included descriptive statistics, chi-square test, and multivariable logistic regression. A risk stratification tool, which included point assignments and measures of performance, was developed. Results: Of 497 temporal artery biopsies for giant cell arteritis performed, 66 were positive and 431 were negative. Jaw/tongue claudication, elevated inflammatory marker values, and age were associated with a positive result. Using our risk stratification tool, 3.4% of low-risk patients, 14.5% of medium-risk patients, and 43.9% of high-risk patients were positive for giant cell arteritis. Conclusions: Jaw/tongue claudication, age, and elevated inflammatory markers were associated with positive biopsy results. Our diagnostic yield was much lower when compared with a benchmark yield determined in a published systematic review. A risk stratification tool was developed based on age and the presence of independent risk factors.
MeSH term(s)	Humans ; Biopsy ; C-Reactive Protein ; Giant Cell Arteritis/diagnosis ; Giant Cell Arteritis/complications ; Giant Cell Arteritis/pathology ; Headache/complications ; Headache/pathology ; Retrospective Studies ; Temporal Arteries/pathology
Chemical Substances	C-Reactive Protein (9007-41-4)
Language	English
Publishing date	2023-01-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	441051-8
ISSN	2379-3961 ; 0043-6542 ; 1098-1861
ISSN (online)	2379-3961
ISSN	0043-6542 ; 1098-1861
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Article ; Online: Strain- and Diet-Related Lesion Variability in Aging DBA/2, C57BL/6, and DBA/2xC57BL/6 F1 Mice.

Harbison, C E / Lipman, R D / Bronson, R T

Veterinary pathology

2016 Volume 53, Issue 2, Page(s) 468–476

Abstract: Genetic and environmental factors both play a role in the occurrence of age-related disease. To examine the genetic contribution to the development of spontaneous lesions in aging animals, a complete range of tissues was comprehensively analyzed by ... ...

Abstract	Genetic and environmental factors both play a role in the occurrence of age-related disease. To examine the genetic contribution to the development of spontaneous lesions in aging animals, a complete range of tissues was comprehensively analyzed by histopathology from 180 individually housed ad libitum-fed or 40% calorically restricted 24-month-old male and female mice of 2 parental strains-DBA/2NNia (D2) and C57BL/6NNia (B6)-and the F1 cross B6D2F1/NNia. Several strain- and diet-dependent patterns of lesions were identified. Many lesions were genotype dependent and exhibited recessive phenotypic expression, defined as being common in 1 parental strain but infrequently observed in the F1 cross (eg, glomerulonephritis in B6 mice), while others were maintained from 1 parental strain to the F1 with similar frequencies (eg, reproductive tract leiomyoma in D2 mice). Other lesions were common regardless of genotype (osteoarthritis, periodontitis). Only rare lesions were more common in the F1 but underrepresented in the 2 parental strains. Furthermore, F1 mice had a lower number of overall total lesions and a lower number of tumors than either parental strain. Caloric restriction reduced the total number of lesions and neoplasms regardless of genotype but differentially affected genotype-dependent lesions in B6 and D2 mice, with B6 mice more sensitive to the effects of caloric restriction than D2 mice. In summary, genetics and environmental factors (eg, dietary restriction) both substantially contribute to the pattern of lesions that develop as animals age.
MeSH term(s)	Aging/pathology ; Animals ; Caloric Restriction ; Diet ; Disease Models, Animal ; Female ; Gene-Environment Interaction ; Genotype ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Neoplasms/genetics ; Neoplasms/pathology ; Phenotype ; Species Specificity
Language	English
Publishing date	2016-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	188012-3
ISSN	1544-2217 ; 0300-9858
ISSN (online)	1544-2217
ISSN	0300-9858
DOI	10.1177/0300985815612152
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Article ; Online: Author Correction: An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-κB.

Min, Junxia / Zaslavsky, Alexander / Fedele, Giuseppe / McLaughlin, Sara K / Reczek, Elizabeth E / De Raedt, Thomas / Guney, Isil / Strochlic, David E / MacConaill, Laura E / Beroukhim, Rameen / Bronson, Roderick T / Ryeom, Sandra / Hahn, William C / Loda, Massimo / Cichowski, Karen

Nature medicine

2024

Language	English
Publishing date	2024-02-21
Publishing country	United States
Document type	Published Erratum
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-024-02866-2
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Article: Plasmodium relictum

Zhang, Xuejin / Meadows, Siobhan N A / Martin, Tori / Doran, Alex / Angles, Rachel / Sander, Samantha / Bronson, Ellen / Witola, William H

International journal for parasitology. Parasites and wildlife

2022 Volume 19, Page(s) 89–95

Abstract: Avian malaria, caused ... ...

Abstract	Avian malaria, caused by
Language	English
Publishing date	2022-08-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2715239-X
ISSN	2213-2244
ISSN	2213-2244
DOI	10.1016/j.ijppaw.2022.08.009
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