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Article: Effects of Nerve Growth Factor-β From Bull Seminal Plasma on Steroidogenesis and Angiogenic Markers of the Bovine Pre-ovulatory Follicle Wall Cell Culture.

Stewart, Jamie L / Gao, Liying / Flaws, Jodi A / Mercadante, Vitor R G / Dias, Nicholas W / Canisso, Igor F / Lima, Fabio S

Frontiers in veterinary science

2022 Volume 8, Page(s) 786480

Abstract: Nerve growth factor-β (NGF) is critical for ovulation in the mammalian ovary and is luteotrophic when administered systemically to camelids and cattle. This study aimed to assess the direct effects of purified bovine NGF on steroidogenesis and angiogenic ...

Abstract	Nerve growth factor-β (NGF) is critical for ovulation in the mammalian ovary and is luteotrophic when administered systemically to camelids and cattle. This study aimed to assess the direct effects of purified bovine NGF on steroidogenesis and angiogenic markers in the bovine pre-ovulatory follicle. Holstein heifers (
Language	English
Publishing date	2022-01-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2021.786480
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Article ; Online: Open-Spaced Ridged Hydrogel Scaffolds Containing TiO

Siddiqui, Ahad M / Thiele, Frederic / Stewart, Rachel N / Rangnick, Simone / Weiss, Georgina J / Chen, Bingkun K / Silvernail, Jodi L / Strickland, Tammy / Nesbitt, Jarred J / Lim, Kelly / Schwarzbauer, Jean E / Schwartz, Jeffrey / Yaszemski, Michael J / Windebank, Anthony J / Madigan, Nicolas N

International journal of molecular sciences

2023 Volume 24, Issue 12

Abstract: The spinal cord has a poor ability to regenerate after an injury, which may be due to cell loss, cyst formation, inflammation, and scarring. A promising approach to treating a spinal cord injury (SCI) is the use of biomaterials. We have developed a novel ...

Abstract	The spinal cord has a poor ability to regenerate after an injury, which may be due to cell loss, cyst formation, inflammation, and scarring. A promising approach to treating a spinal cord injury (SCI) is the use of biomaterials. We have developed a novel hydrogel scaffold fabricated from oligo(poly(ethylene glycol) fumarate) (OPF) as a 0.08 mm thick sheet containing polymer ridges and a cell-attractive surface on the other side. When the cells are cultured on OPF via chemical patterning, the cells attach, align, and deposit ECM along the direction of the pattern. Animals implanted with the rolled scaffold sheets had greater hindlimb recovery compared to that of the multichannel scaffold control, which is likely due to the greater number of axons growing across it. The immune cell number (microglia or hemopoietic cells: 50-120 cells/mm
MeSH term(s)	Rats ; Animals ; Hydrogels/chemistry ; Organophosphonates/metabolism ; Cicatrix/pathology ; Rats, Sprague-Dawley ; Nerve Regeneration ; Spinal Cord Injuries/drug therapy ; Spinal Cord Injuries/metabolism ; Spinal Cord/metabolism ; Axons/pathology ; Tissue Scaffolds/chemistry
Chemical Substances	Hydrogels ; Organophosphonates ; titanium dioxide (15FIX9V2JP) ; poly(ethylene glycol fumarate)
Language	English
Publishing date	2023-06-16
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/ijms241210250
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Article ; Online: Open-Spaced Ridged Hydrogel Scaffolds Containing TiO 2 -Self-Assembled Monolayer of Phosphonates Promote Regeneration and Recovery Following Spinal Cord Injury

Ahad M. Siddiqui / Frederic Thiele / Rachel N. Stewart / Simone Rangnick / Georgina J. Weiss / Bingkun K. Chen / Jodi L. Silvernail / Tammy Strickland / Jarred J. Nesbitt / Kelly Lim / Jean E. Schwarzbauer / Jeffrey Schwartz / Michael J. Yaszemski / Anthony J. Windebank / Nicolas N. Madigan

International Journal of Molecular Sciences, Vol 24, Iss 10250, p

2023 Volume 10250

Abstract	The spinal cord has a poor ability to regenerate after an injury, which may be due to cell loss, cyst formation, inflammation, and scarring. A promising approach to treating a spinal cord injury (SCI) is the use of biomaterials. We have developed a novel hydrogel scaffold fabricated from oligo(poly(ethylene glycol) fumarate) (OPF) as a 0.08 mm thick sheet containing polymer ridges and a cell-attractive surface on the other side. When the cells are cultured on OPF via chemical patterning, the cells attach, align, and deposit ECM along the direction of the pattern. Animals implanted with the rolled scaffold sheets had greater hindlimb recovery compared to that of the multichannel scaffold control, which is likely due to the greater number of axons growing across it. The immune cell number (microglia or hemopoietic cells: 50–120 cells/mm 2 in all conditions), scarring (5–10% in all conditions), and ECM deposits (Laminin or Fibronectin: approximately 10–20% in all conditions) were equal in all conditions. Overall, the results suggest that the scaffold sheets promote axon outgrowth that can be guided across the scaffold, thereby promoting hindlimb recovery. This study provides a hydrogel scaffold construct that can be used in vitro for cell characterization or in vivo for future neuroprosthetics, devices, or cell and ECM delivery.
Keywords	axon regeneration ; biomaterials ; immune cells ; machine learning ; mesenchymal stromal cells (MSCs) ; oligo(poly(ethylene glycol)) fumarate ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Effects of Nerve Growth Factor-β From Bull Seminal Plasma on Steroidogenesis and Angiogenic Markers of the Bovine Pre-ovulatory Follicle Wall Cell Culture

Jamie L. Stewart / Liying Gao / Jodi A. Flaws / Vitor R. G. Mercadante / Nicholas W. Dias / Igor F. Canisso / Fabio S. Lima

Frontiers in Veterinary Science, Vol

2022 Volume 8

Abstract	Nerve growth factor-β (NGF) is critical for ovulation in the mammalian ovary and is luteotrophic when administered systemically to camelids and cattle. This study aimed to assess the direct effects of purified bovine NGF on steroidogenesis and angiogenic markers in the bovine pre-ovulatory follicle. Holstein heifers (n = 2) were synchronized with a standard protocol, and heifers with a preovulatory follicle (≥ 12 mm) had the ovary containing the dominant follicle removed via colpotomy. Pre-ovulatory follicles were dissected into 24 pieces containing theca and granulosa cells that were randomly allocated into culture media supplemented with either purified bovine NGF (100 ng/mL) or untreated (control) for 72 h. The supernatant media was harvested for quantification of progesterone, testosterone, and estradiol concentrations, whereas explants were subjected to mRNA analyses to assess expression of steroidogenic and angiogenic markers. Treatment of follicle wall pieces with NGF upregulated gene expression of steroidogenic enzyme HDS17B (P = 0.04) and increased testosterone production (P < 0.01). However, NGF treatment did not alter production of progesterone (P = 0.81) or estradiol (P = 0.14). Consistently, gene expression of steroidogenic enzymes responsible for producing these hormones (STAR, CYP11A1, HSD3B, CYP17A1, CYP19A1) were unaffected by NGF treatment (P ≥ 0.31). Treatment with NGF downregulated gene expression of the angiogenic enzyme FGF2 (P = 0.02) but did not alter PGES (P = 0.63), VEGFA (P = 0.44), and ESR1 (P = 0.77). Collectively, these results demonstrate that NGF from seminal plasma may interact directly on the theca and granulosa cells of the bovine pre-ovulatory follicle to stimulate testosterone production, which may be secondary to theca cell proliferation. Additionally, decreased FGF2 expression in NGF-treated follicle wall cells suggests hastened onset of follicle wall cellular remodeling that occurs during early luteal development.
Keywords	angiogenesis ; NGF ; granulosa cells ; theca cells ; ruminants ; Veterinary medicine ; SF600-1100
Subject code	610 ; 630
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: Large variation in radiation dose for routine abdomen CT: reasons for excess and easy tips for reduction.

European radiology

2023 Volume 34, Issue 4, Page(s) 2394–2404

Abstract: Objective: To characterize the use and impact of radiation dose reduction techniques in actual practice for routine abdomen CT.: Methods: We retrospectively analyzed consecutive routine abdomen CT scans in adults from a large dose registry, ... ...

Abstract	Objective: To characterize the use and impact of radiation dose reduction techniques in actual practice for routine abdomen CT. Methods: We retrospectively analyzed consecutive routine abdomen CT scans in adults from a large dose registry, contributed by 95 hospitals and imaging facilities. Grouping exams into deciles by, first, patient size, and second, size-adjusted dose length product (DLP), we summarized dose and technical parameters and estimated which parameters contributed most to between-protocols dose variation. Lastly, we modeled the total population dose if all protocols with mean size-adjusted DLP above 433 or 645 mGy-cm were reduced to these thresholds. Results: A total of 748,846 CTs were performed using 1033 unique protocols. When sorted by patient size, patients with larger abdominal diameters had increased dose and effective mAs (milliampere seconds), even after adjusting for patient size. When sorted by size-adjusted dose, patients in the highest versus the lowest decile in size-adjusted DLP received 6.4 times the average dose (1680 vs 265 mGy-cm) even though diameter was no different (312 vs 309 mm). Effective mAs was 2.1-fold higher, unadjusted CTDI Conclusion: There are large variations in radiation doses for routine abdomen CT unrelated to patient size. Modification of kV and single-phase scanning could result in substantial dose reduction. Clinical relevance: Radiation dose-optimization techniques for routine abdomen CT are routinely under-utilized leading to higher doses than needed. Greater modification of technical parameters and number of phases could result in substantial reduction in radiation exposure to patients. Key points: • Based on an analysis of 748,846 routine abdomen CT scans in adults, radiation doses varied tremendously across patients of the same size and optimization techniques were routinely under-utilized. • The difference in observed dose was due to variation in technical parameters and phase count. Automatic exposure control was commonly used to modify effective mAs, whereas kV was rarely adjusted for patient size. Routine abdomen CT should be performed using a single phase, yet multi-phase was common. • kV modulation by patient size and restriction to a single phase for routine abdomen indications could result in substantial reduction in radiation doses using well-established dose optimization approaches.
MeSH term(s)	Adult ; Humans ; Radiation Dosage ; Retrospective Studies ; Tomography, X-Ray Computed/methods ; Abdomen ; Radiation Exposure
Language	English
Publishing date	2023-09-21
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1085366-2
ISSN	1432-1084 ; 0938-7994 ; 1613-3749
ISSN (online)	1432-1084
ISSN	0938-7994 ; 1613-3749
DOI	10.1007/s00330-023-10076-6
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Article ; Online: Do trees grow on money? Auxin as the currency of the cellular economy.

Stewart, Jodi L / Nemhauser, Jennifer L

Cold Spring Harbor perspectives in biology

2010 Volume 2, Issue 2, Page(s) a001420

Abstract: Auxin plays a role in nearly every aspect of a plant's life. Signals from the developmental program, physiological status, and encounters with other organisms all converge on the auxin pathway. The molecular mechanisms facilitating these interactions are ...

Abstract	Auxin plays a role in nearly every aspect of a plant's life. Signals from the developmental program, physiological status, and encounters with other organisms all converge on the auxin pathway. The molecular mechanisms facilitating these interactions are diverse; yet, common themes emerge. Auxin can be regulated by modulating rates of biosynthesis, conjugation, and transport, as well as sensitivity of a cell to the auxin signal. In this article, we describe some well-studied examples of auxin's interactions with other pathways.
MeSH term(s)	Arabidopsis/metabolism ; Biological Transport ; Gene Expression Regulation, Plant ; Indoleacetic Acids/metabolism ; Models, Biological ; Models, Genetic ; Mutation ; Phenotype ; Plant Growth Regulators/metabolism ; Plant Physiological Phenomena ; Plants/metabolism ; Signal Transduction ; Trees
Chemical Substances	Indoleacetic Acids ; Plant Growth Regulators
Language	English
Publishing date	2010-02-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ISSN	1943-0264
ISSN (online)	1943-0264
DOI	10.1101/cshperspect.a001420
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Article: Increased spatial coupling of integrin and collagen IV in the immunoresistant clear cell renal cell carcinoma tumor microenvironment.

Soupir, Alex C / Hayes, Mitchell T / Peak, Taylor C / Ospina, Oscar / Chakiryan, Nicholas H / Berglund, Anders E / Stewart, Paul A / Nguyen, Jonathan / Segura, Carlos Moran / Francis, Natasha L / Echevarria, Paola M Ramos / Chahoud, Jad / Li, Roger / Tsai, Kenneth Y / Balasi, Jodi A / Peres, Yamila Caraballo / Dhillon, Jasreman / Martinez, Lindsey A / Gloria, Warren E /

Schurman, Nathan / Kim, Sean / Gregory, Mark / Mulé, James / Fridley, Brooke L / Manley, Brandon J

bioRxiv : the preprint server for biology

2023

Abstract: Background: Immunotherapy (IO) has improved survival for patients with advanced clear cell renal cell carcinoma (ccRCC), but resistance to therapy develops in most patients. We use cellular-resolution spatial transcriptomics in patients with IO naïve ... ...

Abstract	Background: Immunotherapy (IO) has improved survival for patients with advanced clear cell renal cell carcinoma (ccRCC), but resistance to therapy develops in most patients. We use cellular-resolution spatial transcriptomics in patients with IO naïve and IO exposed primary ccRCC tumors to better understand IO resistance. Spatial molecular imaging (SMI) was obtained for tumor and adjacent stroma samples. Spatial gene set enrichment analysis (GSEA) and autocorrelation (coupling with high expression) of ligand-receptor transcript pairs were assessed. Multiplex immunofluorescence (mIF) validation was used for significant autocorrelative findings and the cancer genome atlas (TCGA) and the clinical proteomic tumor analysis consortium (CPTAC) databases were queried to assess bulk RNA expression and proteomic correlates. Results: 21 patient samples underwent SMI. Viable tumors following IO harbored more stromal CD8+ T cells and neutrophils than IO naïve tumors. Conclusions: On spatial transcriptomics,
Language	English
Publishing date	2023-11-17
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.11.16.567457
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Article ; Online: Structural Characterization of Degrader-Induced Ternary Complexes Using Hydrogen-Deuterium Exchange Mass Spectrometry and Computational Modeling: Implications for Structure-Based Design.

Eron, Scott J / Huang, Hongwei / Agafonov, Roman V / Fitzgerald, Mark E / Patel, Joe / Michael, Ryan E / Lee, Tobie D / Hart, Ashley A / Shaulsky, Jodi / Nasveschuk, Christopher G / Phillips, Andrew J / Fisher, Stewart L / Good, Andrew

ACS chemical biology

2021 Volume 16, Issue 11, Page(s) 2228–2243

Abstract: The field of targeted protein degradation (TPD) has grown exponentially over the past decade with the goal of developing therapies that mark proteins for destruction leveraging the ubiquitin-proteasome system. One common approach to achieve TPD is to ... ...

Abstract	The field of targeted protein degradation (TPD) has grown exponentially over the past decade with the goal of developing therapies that mark proteins for destruction leveraging the ubiquitin-proteasome system. One common approach to achieve TPD is to employ a heterobifunctional molecule, termed as a degrader, to recruit the protein target of interest to the E3 ligase machinery. The resultant generation of an intermediary ternary complex (target-degrader-ligase) is pivotal in the degradation process. Understanding the ternary complex geometry offers valuable insight into selectivity, catalytic efficiency, linker chemistry, and rational degrader design. In this study, we utilize hydrogen-deuterium exchange mass spectrometry (HDX-MS) to identify degrader-induced protein-protein interfaces. We then use these data in conjunction with constrained protein docking to build three-dimensional models of the ternary complex. The approach was used to characterize complex formation between the E3 ligase CRBN and the first bromodomain of BRD4, a prominent oncology target. We show marked differences in the ternary complexes formed in solution based on distinct patterns of deuterium uptake for two degraders, CFT-1297 and dBET6. CFT-1297, which exhibited positive cooperativity, altered the deuterium uptake profile revealing the degrader-induced protein-protein interface of the ternary complex. For CFT-1297, the ternary complexes generated by the highest scoring HDX-constrained docking models differ markedly from those observed in the published crystal structures. These results highlight the potential utility of HDX-MS to provide rapidly accessible structural insights into degrader-induced protein-protein interfaces in solution. They further suggest that degrader ternary complexes exhibit significant conformation flexibility and that biologically relevant complexes may well not exhibit the largest interaction surfaces between proteins. Taken together, the results indicate that methods capable of incorporating linker conformation uncertainty may prove an important component in degrader design moving forward. In addition, the development of scoring functions modified to handle interfaces with no evolved complementarity, for example, through consideration of high levels of water infiltration, may prove valuable. Furthermore, the use of crystal structures as validation tools for novel degrader methods needs to be considered with caution.
MeSH term(s)	Acetamides/chemistry ; Acetamides/pharmacology ; Cell Cycle Proteins/chemistry ; Computer Simulation ; Deuterium Exchange Measurement ; Gene Expression Regulation/drug effects ; HEK293 Cells ; Humans ; Indoles/chemistry ; Indoles/pharmacology ; Mass Spectrometry/methods ; Models, Chemical ; Models, Molecular ; Molecular Structure ; Piperidines/chemistry ; Piperidines/pharmacology ; Protein Conformation ; Transcription Factors/chemistry
Chemical Substances	Acetamides ; BRD4 protein, human ; Cell Cycle Proteins ; Indoles ; Piperidines ; Transcription Factors ; dBET6
Language	English
Publishing date	2021-09-28
Publishing country	United States
Document type	Journal Article
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/acschembio.1c00376
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Article ; Online: PIF genes mediate the effect of sucrose on seedling growth dynamics.

Stewart, Jodi L / Maloof, Julin N / Nemhauser, Jennifer L

PloS one

2011 Volume 6, Issue 5, Page(s) e19894

Abstract: As photoautotrophs, plants can use both the form and amount of fixed carbon as a measure of the light environment. In this study, we used a variety of approaches to elucidate the role of exogenous sucrose in modifying seedling growth dynamics. In ... ...

Abstract	As photoautotrophs, plants can use both the form and amount of fixed carbon as a measure of the light environment. In this study, we used a variety of approaches to elucidate the role of exogenous sucrose in modifying seedling growth dynamics. In addition to its known effects on germination, high-resolution temporal analysis revealed that sucrose could extend the number of days plants exhibited rapid hypocotyl elongation, leading to dramatic increases in ultimate seedling height. In addition, sucrose changed the timing of daily growth maxima, demonstrating that diel growth dynamics are more plastic than previously suspected. Sucrose-dependent growth promotion required function of multiple phytochrome-interacting factors (PIFs), and overexpression of PIF5 led to growth dynamics similar to plants exposed to sucrose. Consistent with this result, sucrose was found to increase levels of PIF5 protein. PIFs have well-established roles as integrators of response to light levels, time of day and phytohormone signaling. Our findings strongly suggest that carbon availability can modify the known photomorphogenetic signaling network.
MeSH term(s)	Arabidopsis/drug effects ; Arabidopsis/genetics ; Arabidopsis/growth & development ; Arabidopsis Proteins/genetics ; Arabidopsis Proteins/metabolism ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Blotting, Western ; Gene Expression Regulation, Plant/drug effects ; Germination/drug effects ; Hypocotyl/drug effects ; Hypocotyl/genetics ; Hypocotyl/growth & development ; Light ; Phytochrome/pharmacology ; RNA, Messenger/genetics ; RNA, Plant/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Seedlings/drug effects ; Seedlings/genetics ; Seedlings/growth & development ; Sucrose/pharmacology
Chemical Substances	Arabidopsis Proteins ; Basic Helix-Loop-Helix Transcription Factors ; PIF1 protein, Arabidopsis ; PIF5 protein, Arabidopsis ; RNA, Messenger ; RNA, Plant ; Phytochrome (11121-56-5) ; Sucrose (57-50-1)
Language	English
Publishing date	2011-05-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0019894
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Article ; Online: Cardiovascular autonomic responses in patients with Parkinson disease to pedunculopontine deep brain stimulation.

Hyam, Jonathan A / Roy, Holly A / Huang, Yongzhi / Martin, Sean / Wang, Shouyan / Rippey, Jodi / Coyne, Terry J / Stewart, Ian / Kerr, Graham / Silburn, Peter / Paterson, David J / Aziz, Tipu Z / Green, Alexander L

Clinical autonomic research : official journal of the Clinical Autonomic Research Society

2019 Volume 29, Issue 6, Page(s) 615–624

Abstract: Purpose: Dysautonomia can be a debilitating feature of Parkinson disease (PD). Pedunculopontine nucleus (PPN) stimulation may improve gait disorders in PD, and may also result in changes in autonomic performance.: Methods: To determine whether ... ...

Abstract	Purpose: Dysautonomia can be a debilitating feature of Parkinson disease (PD). Pedunculopontine nucleus (PPN) stimulation may improve gait disorders in PD, and may also result in changes in autonomic performance. Methods: To determine whether pedunculopontine nucleus stimulation improves cardiovascular responses to autonomic challenges of postural tilt and Valsalva manoeuver, eight patients with pedunculopontine nucleus deep brain stimulation were recruited to the study; two were excluded for technical reasons during testing. Participants underwent head up tilt and Valsalva manoeuver with stimulation turned ON and OFF. Continuous blood pressure and ECG waveforms were recorded during these tests. In a single patient, local field potential activity was recorded from the implanted electrode during tilt. Results: The fall in systolic blood pressure after tilt was significantly smaller with stimulation ON (mean - 8.3% versus - 17.2%, p = 0.044). Valsalva ratio increased with stimulation from median 1.15 OFF to 1.20 ON (p = 0.028). Baroreflex sensitivity increased during Valsalva compared to rest with stimulation ON versus OFF (p = 0.028). The increase in baroreflex sensitivity correlated significantly with the mean depth of PPN stimulating electrode contacts. This accounted for 89% of its variance (r = 0.943, p = 0.005). Conclusion: PPN stimulation can modulate the cardiovascular system in patients with PD. In this study, it reduced the postural fall in systolic blood pressure during head-up tilt and improved the cardiovascular response during Valsalva, presumably by altering the neural control of baroreflex activation.
MeSH term(s)	Aged ; Deep Brain Stimulation/methods ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/complications ; Parkinson Disease/therapy ; Pedunculopontine Tegmental Nucleus/physiology ; Primary Dysautonomias/etiology ; Tilt-Table Test ; Valsalva Maneuver
Language	English
Publishing date	2019-09-06
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1080007-4
ISSN	1619-1560 ; 0959-9851
ISSN (online)	1619-1560
ISSN	0959-9851
DOI	10.1007/s10286-019-00634-8
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