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Article ; Online: Characterization of a polyclonal antibody that is highly selective for the D-isoAsp-25 variant of mammalian histone H2B.

Aswad, Dana W / O'Leary, Kevin S / Williams, Katherine

2023 Volume 55, Issue 4, Page(s) 541–544

Abstract: Approximately 12% of histone H2B molecules in mammalian brain contain a modification wherein Asp25 is present as the D-enantiomer, and is mostly linked to Gly26 via the side-chain carboxyl. Here we (1) demonstrate the high specificity of a polyclonal ... ...

Abstract	Approximately 12% of histone H2B molecules in mammalian brain contain a modification wherein Asp25 is present as the D-enantiomer, and is mostly linked to Gly26 via the side-chain carboxyl. Here we (1) demonstrate the high specificity of a polyclonal antibody to this modification, and (2) use this Ab to demonstrate that this modification is enriched in brain relative to liver, thymus, and HeLa cells.
MeSH term(s)	Animals ; Humans ; Histones/genetics ; Histones/metabolism ; HeLa Cells ; Antibodies ; Mammals/metabolism ; Brain/metabolism ; Chromatin
Chemical Substances	Histones ; Antibodies ; Chromatin
Language	English
Publishing date	2023-01-30
Publishing country	Austria
Document type	Journal Article
ZDB-ID	1121341-3
ISSN	1438-2199 ; 0939-4451
ISSN (online)	1438-2199
ISSN	0939-4451
DOI	10.1007/s00726-023-03242-z
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Article: Leptin-inhibited neurons in the lateral parabrachial nucleus do not alter food intake or glucose balance.

Park, Seahyung / Williams, Kevin W / Sohn, Jong-Woo

Animal cells and systems

2022 Volume 26, Issue 3, Page(s) 92–98

Abstract: The lateral parabrachial nucleus (LPBN) has been shown to be involved in the suppression of appetite at the pharmacological, optogenetic and chemogenetic levels. However, the signalling that mediates activation of these neurons in physiological ... ...

Abstract	The lateral parabrachial nucleus (LPBN) has been shown to be involved in the suppression of appetite at the pharmacological, optogenetic and chemogenetic levels. However, the signalling that mediates activation of these neurons in physiological conditions has been hindered by difficulties in segregating different cell populations in this region. Using reporter mice, we identify at the electrophysiological level the effects of an anorexic hormone, leptin, on leptin receptor (ObR)-expressing neurons in the LPBN (LPBN
Language	English
Publishing date	2022-06-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2562988-8
ISSN	2151-2485 ; 1976-8354
ISSN (online)	2151-2485
ISSN	1976-8354
DOI	10.1080/19768354.2022.2084159
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Article ; Online: Leptin-inhibited neurons in the lateral parabrachial nucleus do not alter food intake or glucose balance

Seahyung Park / Kevin W. Williams / Jong-Woo Sohn

Animal Cells and Systems, Vol 26, Iss 3, Pp 92-

2022 Volume 98

Abstract	The lateral parabrachial nucleus (LPBN) has been shown to be involved in the suppression of appetite at the pharmacological, optogenetic and chemogenetic levels. However, the signalling that mediates activation of these neurons in physiological conditions has been hindered by difficulties in segregating different cell populations in this region. Using reporter mice, we identify at the electrophysiological level the effects of an anorexic hormone, leptin, on leptin receptor (ObR)-expressing neurons in the LPBN (LPBNObR neurons). Application of leptin caused inhibition in a subpopulation of LPBNObR neurons. This effect was mediated by an increased potassium conductance and was also accompanied by a decrease in excitatory synaptic input onto these neurons. However, mimicking the inhibitory effects of leptin on LPBNObR neurons through chemogenetics led to no changes in feeding or glucose levels, which suggests that leptin action on LPBNObR neurons may not be sufficient to regulate these metabolic aspects.
Keywords	Appetite ; glucose ; leptin ; parabrachial nucleus ; chemogenetics ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Taylor & Francis Group
Document type	Article ; Online
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Article ; Online: Feasibility and Intermediate Results of Transcarotid Revascularization with a Prosthetic Conduit.

Cui, Christina L / Reardon, Emily S / Loanzon, Roberto S / Williams, Zachary F / Cox, Mitchell W / Southerland, Kevin W

Annals of vascular surgery

2024 Volume 103, Page(s) 74–80

Abstract: Background: Transcarotid artery revascularization (TCAR) is a hybrid technique with excellent initial outcomes. The technical success and safety of TCAR is heavily dependent on an anatomically suitable common carotid artery (CCA). Many patients do not ... ...

Abstract	Background: Transcarotid artery revascularization (TCAR) is a hybrid technique with excellent initial outcomes. The technical success and safety of TCAR is heavily dependent on an anatomically suitable common carotid artery (CCA). Many patients do not meet anatomic criteria and therefore are not eligible for this therapy. We sought to extend the eligibility of TCAR to patients with unfavorable CCA anatomy via the adoption of a prosthetic arterial conduit. Methods: A single-center retrospective study of patients with critical carotid artery stenosis who underwent TCAR via a prosthetic conduit between June 2019 and October 2021 was performed. All patients in the study were considered high-risk for carotid endarterectomy based on anatomic features, such as restenosis post-carotid endarterectomy and neck radiation. Unfavorable CCA anatomy was defined as a clavicle to carotid bifurcation distance <5 cm, a CCA diameter <6 mm, and/or significant atherosclerotic disease at the intended arterial access site. The primary outcome of interest was technical success. Secondary outcomes included perioperative complications, intermediate and long-term patency, intermediate and long-term stroke and/or mortality and in-hospital length of stay. Follow-up ranged from 1 to 29 months. Results: Eight patients underwent 10 TCAR procedures via a prosthetic conduit. A total of 2 procedures (20%) were performed on female patients and 8 procedures (75%) were performed on male patients. The mean age was 65 years old (standard deviation 11 years). Technical success was 100%. The 30-day ipsilateral stroke rate was 0%. The 30-day patency was 90%. There was no re-exploration for hemorrhage and 30 day mortality was 0%. Conclusions: TCAR is an excellent option for carotid artery revascularization. Unfavorable CCA anatomy has limited its applicability. TCAR via a prosthetic conduit has the potential to expand eligibility for this promising therapy.
Language	English
Publishing date	2024-02-22
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1027366-9
ISSN	1615-5947 ; 0890-5096
ISSN (online)	1615-5947
ISSN	0890-5096
DOI	10.1016/j.avsg.2023.12.075
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Article ; Online: Lipidomic changes in a novel sepsis outcome-based analysis reveals potent pro-inflammatory and pro-resolving signaling lipids.

Sulaiman, Dawoud / Wu, Dongyuan / Black, Lauren Page / Williams, Kevin J / Graim, Kiley / Datta, Susmita / Reddy, Srinivasa T / Guirgis, Faheem W

Clinical and translational science

2024 Volume 17, Issue 3, Page(s) e13745

Abstract: The purpose of this study was to investigate changes in the lipidome of patients with sepsis to identify signaling lipids associated with poor outcomes that could be linked to future therapies. Adult patients with sepsis were enrolled within 24h of ... ...

Abstract	The purpose of this study was to investigate changes in the lipidome of patients with sepsis to identify signaling lipids associated with poor outcomes that could be linked to future therapies. Adult patients with sepsis were enrolled within 24h of sepsis recognition. Patients meeting Sepsis-3 criteria were enrolled from the emergency department or intensive care unit and blood samples were obtained. Clinical data were collected and outcomes of rapid recovery, chronic critical illness (CCI), or early death were adjudicated by clinicians. Lipidomic analysis was performed on two platforms, the Sciex™ 5500 device to perform a lipidomic screen of 1450 lipid species and a targeted signaling lipid panel using liquid-chromatography tandem mass spectrometry. For the lipidomic screen, there were 274 patients with sepsis: 192 with rapid recovery, 47 with CCI, and 35 with early deaths. CCI and early death patients were grouped together for analysis. Fatty acid (FA) 12:0 was decreased in CCI/early death, whereas FA 17:0 and 20:1 were elevated in CCI/early death, compared to rapid recovery patients. For the signaling lipid panel analysis, there were 262 patients with sepsis: 189 with rapid recovery, 45 with CCI, and 28 with early death. Pro-inflammatory signaling lipids from ω-6 poly-unsaturated fatty acids (PUFAs), including 15-hydroxyeicosatetraenoic (HETE), 12-HETE, and 11-HETE (oxidation products of arachidonic acid [AA]) were elevated in CCI/early death patients compared to rapid recovery. The pro-resolving lipid mediator from ω-3 PUFAs, 14(S)-hydroxy docosahexaenoic acid (14S-HDHA), was also elevated in CCI/early death compared to rapid recovery. Signaling lipids of the AA pathway were elevated in poor-outcome patients with sepsis and may serve as targets for future therapies.
MeSH term(s)	Adult ; Humans ; Lipidomics ; Fatty Acids, Omega-3 ; Sepsis ; Fatty Acids ; Mass Spectrometry
Chemical Substances	Fatty Acids, Omega-3 ; Fatty Acids
Language	English
Publishing date	2024-03-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2433157-0
ISSN	1752-8062 ; 1752-8054
ISSN (online)	1752-8062
ISSN	1752-8054
DOI	10.1111/cts.13745
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Article ; Online: Surgical outcomes of patients with inferior vena cava leiomyosarcoma.

Shafique, Hana S / Commander, Sarah Jane / Blazer, Dan G / Kim, Young / Southerland, Kevin W / Williams, Zachary F

Journal of vascular surgery. Venous and lymphatic disorders

2024 , Page(s) 101885

Abstract: Introduction: Primary vascular leiomyosarcomas are incredibly rare and have a poor prognosis. The purpose of this study was to analyze the surgical outcomes of patients with primary inferior vena cava (IVC) leiomyosarcoma.: Methods: We performed a ... ...

Abstract	Introduction: Primary vascular leiomyosarcomas are incredibly rare and have a poor prognosis. The purpose of this study was to analyze the surgical outcomes of patients with primary inferior vena cava (IVC) leiomyosarcoma. Methods: We performed a retrospective review of IVC leiomyosarcoma resections performed at a single tertiary care hospital from 2014 to 2023. A total of 13 cases were analyzed, including 10 women and 3 men. The presenting symptoms, tumor characteristics, operative management, postoperative complications, and survival rates were assessed for each patient. Results: The median patient age was 59 years (quartile [Q]1, 52 years; Q3, 68 years). The median tumor size was 7.0 cm (Q1, 6 cm; Q3, 12 cm). The median mitotic rate was 6 per 10 high-power fields (Q1, 2.5; Q3, 15.5). All 13 patients underwent grossly negative tumor resection, with 9 (69%) having microscopically negative margins (R0). No patient had lymph node involvement. The IVCs were managed with ligation in four patients for tumors already occluding the IVC and bovine pericardial patch angioplasty in seven patients or primary repair in two patients for patent IVCs. Concomitant right nephrectomy was performed in seven patients. Left renal vein ligation was performed in three patients, but no left nephrectomies were performed. Significant postoperative complications included one patient with lower extremity compartment syndrome, two patients with severe leg swelling, and one patient with arm swelling. The 30-day mortality rate was zero. Using the Kaplan-Meier product limit method, disease-specific survival was estimated to be 93%. Conclusions: Surgical resection is a feasible and effective oncologic treatment option for patients with IVC leiomyosarcoma. The IVC can be safely managed by ligation, primary repair, or patch angioplasty, depending on the prior patency of the IVC.
Language	English
Publishing date	2024-03-27
Publishing country	United States
Document type	Journal Article
ISSN	2213-3348
ISSN (online)	2213-3348
DOI	10.1016/j.jvsv.2024.101885
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Article ; Online: Surface‐to‐tile drain connectivity and phosphorus transport: Effect of antecedent soil moisture

Williams, Mark R. / Penn, Chad J. / King, Kevin W. / McAfee, Scott J.

Hydrological Processes. 2023 Mar., v. 37, no. 3 p.e14831-

2023

Abstract: Macropores connecting surface soils to tile drains can alter water and nutrient transport through the subsurface. In this study, laboratory rainfall simulations with artificial macropores combined with edge‐of‐field monitoring were used to evaluate ... ...

Abstract	Macropores connecting surface soils to tile drains can alter water and nutrient transport through the subsurface. In this study, laboratory rainfall simulations with artificial macropores combined with edge‐of‐field monitoring were used to evaluate surface‐to‐tile drain connectivity and phosphorus (P) transport as a function of antecedent moisture conditions. Laboratory rainfall simulations using repacked soil boxes with different macropore layouts (i.e., no macropore, surface‐connected macropores, and disconnected macropores) were used to examine changes in water sources and flow pathways to tile drains with varying degrees of connectivity and antecedent wetness. Water, tracer, and P fluxes from a tile‐drained field were also monitored to quantify linkages among water flow pathways, antecedent wetness, and P delivery to tile drains. Both laboratory and field results showed that surface‐to‐tile drain connectivity was important for water transport through the subsurface under both dry and wet antecedent conditions. When soil conditions were dry, discharge was minimal and primarily comprised of event water that bypassed the soil matrix. Increasing wetness resulted in similar event water transport, but greater mobilization of stored pre‐event water and greater discharge; thus, the dominant source of tile water and the magnitude of tile discharge were substantially altered with changing antecedent moisture. Field data revealed that changes in drainage water source and discharge with increasing wetness impacted dissolved P transport. Dissolved P concentration decreased and loading increased with increasing wetness. Findings indicate that greater mobilization of pre‐event water under wet antecedent conditions acted as both a hydrologic and chemical buffer for subsurface dissolved P transport. Comparison of study results to water quality data from a larger edge‐of‐field network suggest that relationships between antecedent moisture conditions, water flow pathways, and P transport from the current study are broadly applicable across tile‐drained fields. Understanding processes controlling P delivery to tile drains has direct applicability for conservation practice implementation and improving process representation in models.
Keywords	antecedent moisture ; conservation practices ; drainage water ; macropores ; nutrient transport ; phosphorus ; rain ; soil water ; tile drainage ; water flow ; water quality
Language	English
Dates of publication	2023-03
Publishing place	John Wiley & Sons, Inc.
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	1479953-4
ISSN	1099-1085 ; 0885-6087
ISSN (online)	1099-1085
ISSN	0885-6087
DOI	10.1002/hyp.14831
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Exercise-induced hypothalamic neuroplasticity: Implications for energy and glucose metabolism.

Hwang, Eunsang / Portillo, Bryan / Grose, Kyle / Fujikawa, Teppei / Williams, Kevin W

Molecular metabolism

2023 Volume 73, Page(s) 101745

Abstract: Background: Neuroplasticity refers to the brain's ability to undergo functional and structural changes in response to diverse challenges. Converging evidence supports the notion that exercise serves as a metabolic challenge, triggering the release of ... ...

Abstract	Background: Neuroplasticity refers to the brain's ability to undergo functional and structural changes in response to diverse challenges. Converging evidence supports the notion that exercise serves as a metabolic challenge, triggering the release of multiple factors both in the periphery and within the brain. These factors actively contribute to plasticity in the brain, and in turn, regulate energy and glucose metabolism. Scope of review: The primary focus of this review is to explore the impact of exercise-induced plasticity in the brain on metabolic homeostasis, with an emphasis on the role of the hypothalamus in this process. Additionally, the review provides an overview of various factors induced by exercise that contribute to energy balance and glucose metabolism. Notably, these factors exert their effects, at least in part, through actions within the hypothalamus and more broadly in the central nervous system. Major conclusions: Exercise elicits both transient and sustained changes in metabolism, accompanied by changes in neural activity within specific brain regions. Importantly, the contribution of exercise-induced plasticity and the underlying mechanisms by which neuroplasticity influences the effects of exercise are not well understood. Recent work has begun to overcome this gap in knowledge by examining the complex interactions of exercise-induced factors which alter neural circuit properties to influence metabolism.
MeSH term(s)	Hypothalamus/metabolism ; Exercise/physiology ; Brain/metabolism ; Neuronal Plasticity/physiology ; Glucose/metabolism
Chemical Substances	Glucose (IY9XDZ35W2)
Language	English
Publishing date	2023-05-31
Publishing country	Germany
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2708735-9
ISSN	2212-8778 ; 2212-8778
ISSN (online)	2212-8778
ISSN	2212-8778
DOI	10.1016/j.molmet.2023.101745
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Article: Leptin-inhibited neurons in the lateral parabrachial nucleus do not alter food intake or glucose balance

Park, Seahyung / Williams, Kevin W. / Sohn, Jong-Woo

Animal cells and systems. 2022 May 04, v. 26, no. 3

2022

Abstract	The lateral parabrachial nucleus (LPBN) has been shown to be involved in the suppression of appetite at the pharmacological, optogenetic and chemogenetic levels. However, the signalling that mediates activation of these neurons in physiological conditions has been hindered by difficulties in segregating different cell populations in this region. Using reporter mice, we identify at the electrophysiological level the effects of an anorexic hormone, leptin, on leptin receptor (ObR)-expressing neurons in the LPBN (LPBNᴼᵇᴿ neurons). Application of leptin caused inhibition in a subpopulation of LPBNᴼᵇᴿ neurons. This effect was mediated by an increased potassium conductance and was also accompanied by a decrease in excitatory synaptic input onto these neurons. However, mimicking the inhibitory effects of leptin on LPBNᴼᵇᴿ neurons through chemogenetics led to no changes in feeding or glucose levels, which suggests that leptin action on LPBNᴼᵇᴿ neurons may not be sufficient to regulate these metabolic aspects.
Keywords	appetite ; electrophysiology ; food intake ; glucose ; leptin ; leptin receptors ; optogenetics ; potassium ; synaptic transmission
Language	English
Dates of publication	2022-0504
Size	p. 92-98.
Publishing place	Taylor & Francis
Document type	Article
ZDB-ID	2562988-8
ISSN	2151-2485 ; 1976-8354
ISSN (online)	2151-2485
ISSN	1976-8354
DOI	10.1080/19768354.2022.2084159
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Sex-based differences in outcomes after lower extremity bypass for chronic limb-threatening ischemia.

Kim, Young / Weissler, E Hope / Long, Chandler A / Williams, Zachary F / Dua, Anahita / Southerland, Kevin W

Atherosclerosis

2023 Volume 384, Page(s) 117157

Abstract: Background and aims: Lower extremity bypass surgery is an effective treatment option for patients with chronic limb-threatening ischemia (CLTI). Recent studies have suggested that sex-based differences may impact patient outcomes following lower ... ...

Abstract	Background and aims: Lower extremity bypass surgery is an effective treatment option for patients with chronic limb-threatening ischemia (CLTI). Recent studies have suggested that sex-based differences may impact patient outcomes following lower extremity revascularization, however, results have been inconsistent. Methods: In this multicenter analysis, we retrospectively identified all infrainguinal bypass procedures performed for CLTI from 2002 to 2021. Patients were separated into two groups based on sex. Primary outcomes were major limb amputation and reintervention for graft patency. Results: Of 843 bypasses performed over the study period, 347 (41.2%) patients were female. Racial/ethnic distribution and medical comorbidities were similar across sex groups. Surgical indications and operative details were also similar between groups, including conduit type (49.9% autogenous), bypass target (65.4% infrageniculate), and concurrent endarterectomy (38.9%). Female and male patients had similar hospital length of stay (6 days [4-9] vs 6 days [4-9]), hospital readmission (25.6% vs 25.0%), and postoperative complications (p=NS each). Female patients had higher major amputation rates (10.1% vs 6.3%, p=0.04) after one year, whereas reintervention rates were similar between groups (26.2% vs 24.6%, p=NS). After accounting for patient factors, female sex (odds ratio [OR] 1.02 [1.00-1.04]), infrageniculate target (OR 1.02 [1.00-1.04]), and bypass for tissue loss (OR 1.02 [1.00-1.04]) were associated with major amputation after bypass (p<0.05 each). Conclusions: Female sex is associated with a small but significant increase major amputation after lower extremity bypass surgery for CLTI, despite similar clinical presentation, medical comorbidities, and operative details. These data support the increasingly recognized sex disparities in peripheral arterial disease.
MeSH term(s)	Humans ; Male ; Female ; Chronic Limb-Threatening Ischemia ; Risk Factors ; Retrospective Studies ; Limb Salvage/adverse effects ; Limb Salvage/methods ; Ischemia/surgery ; Peripheral Arterial Disease ; Treatment Outcome ; Postoperative Complications/etiology ; Lower Extremity/surgery ; Endovascular Procedures/adverse effects
Language	English
Publishing date	2023-06-07
Publishing country	Ireland
Document type	Multicenter Study ; Journal Article
ZDB-ID	80061-2
ISSN	1879-1484 ; 0021-9150
ISSN (online)	1879-1484
ISSN	0021-9150
DOI	10.1016/j.atherosclerosis.2023.06.004
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