bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depletion of white adipocyte progenitors suppresses obesity development (LB763)
Authors: Daquinag Alexes , Tseng Chieh , Salameh Ahmad , Zhang Yan , Kolonin Mikhail 
Published: June 2021

The study objective is to test a new approach to obesity prevention. Overgrowth of white adipose tissue (WAT) in obesity occurs as a result of adipocyte hypertrophy and hyperplasia. Expansion and renewal of adipocytes relies on proliferation and differentiation of white adipocyte progenitors (WAP), however, the requirement of WAP for obesity development has not been proven. Here, we investigate whether depletion of WAP can be used to prevent WAT expansion. We test this approach by using a hunter‐killer peptide designed to induce apoptosis selectively in WAP. We show that targeted WAP cytoablation results in a long‐term WAT growth suppression despite increased caloric intake in a mouse diet‐induced obesity model. Our data indicate that WAP depletion results in a compensatory beige adipocyte differentiation from an alternative progenitor cell population. Consistent with reported thermogenic capacity of beige adipose tissue, WAP‐depleted mice display increased energy expenditure. We conclude that targeting of adipocyte progenitors could be developed as a strategy to modulate WAT metabolic activity.Grant Funding Source: American Heart Association and Cancer Prevention and Research Institute of Texas
Artemisia scoparia enhances adipocyte development and endocrine function in vitro and enhances insulin action in vivo (LB771)
Authors: Fuller Scott , Richard Allison , Fedorcenco Veaceslav , Ribnicky David , Stephens Jacqueline 
Published: June 2021

Background: Failure of adipocytes to expand during periods of energy excess can result in undesirable metabolic consequences. Blinded screening studies have indicated that Artemisia scoparia (SCO) extracts can enhance adipocyte differentiation and lipid accumulation in cultured adipocytes. The present study tested the hypothesis that SCO treatment modulates fat cell development and function in vitro and insulin sensitivity in adipose tissue in vivo.Methods: In vitro experiments utilized a Gal4‐PPAR[[Unsupported Character ‐ Symbol Font □]] ligand binding domain (LBD) fusion protein‐luciferase reporter assay to examine PPAR[[Unsupported Character ‐ Symbol Font □]] activation. Neutral lipid accumulation, gene expression, and protein secretion were measured by Oil Red O staining, qRT‐PCR, and immunoblotting, respectively. For the in vivo experiments, diet‐induced obese (DIO) C57BL/6J mice were fed a high‐fat diet (HFD) or HFD containing 1% w/w SCO for four weeks. Body weight and composition, food intake, and fasting glucose and insulin levels were measured. Phospho‐activation and expression of insulin‐sensitizing proteins in epididymal adipose tissue (eWAT) were measured by immunoblotting.Results: Ethanolic extracts of A. scoparia significantly activated the PPAR[[Unsupported Character ‐ Symbol Font □]] LBD and enhanced lipid accumulation in differentiating 3T3‐L1 cells. SCO increased the transcription of several PPAR[[Unsupported Character ‐ Symbol Font □]] target genes in differentiating 3T3‐L1 cells and rescued the negative effects of tumor necrosis factor [[Unsupported Character ‐ Symbol Font □]] on production and secretion of adiponectin and monocyte chemoattractant protein‐1 in fully differentiated fat cells. DIO mice treated with SCO had elevated adiponectin levels and increased phosphorylation of AMPK[[Unsupported Character ‐ Symbol Font □]] in eWAT when compared to control mice. In SCO‐treated mice, these changes were also associated with decreased fasting insulin and glucose levels.Conclusion: SCO has metabolically beneficial effects on adipocytes in vitro and adipose tissue in vivo, highlighting its potential as a metabolically favorable botanical supplement.Grant Funding Source: Supported by NIH 2P30DK072476
Role of endothelial connexin 43 during recovery from lipopolysaccharide‐induced lung injury in rats (LB784)
Authors: Kandasamy Kathirvel , Escue Rachel , Parthasarathi Kaushik 
Published: June 2021

We showed endothelial Cx43 gap junctions mediate permeability in lung microvessels. However, whether Cx43 gap junctions modulate lung microvessel permeability during recovery from an inflammatory insult is unknown. Toward this, we instilled rats with lipopolysaccharide (LPS; 2mg/kg; IT). Rats were allowed to recover for 1, 5 or 14 days. At each recovery period, the animals’ lungs were isolated and perfused with autologous blood. The pulmonary artery, left atrial and airway pressures were maintained at 10, 3 and 5 cmH2O, respectively. Via a left atrial microcatheter, we loaded microvessels with the Ca2+ indicator, fluo4 AM and Ca2+ cage, NP‐EGTA AM. Uncaging in microvessels of untreated control lungs revealed that, fluo4 fluorescence increased by 39±11% (mean±SEM; n=5 vessels) at 80 µm from the uncaging site compared to that at 0 µm. In contrast, at 5 days post‐LPS treatment the fluorescence increased only 6±2% (P<0.05, n=6). At day 14, fluorescence increase was back at control levels. Further, we determined single microvessel permeability via normalized fluorescence of FITC‐dextran (FDx20) infused into microvessels. The permeability was high at day 1 post LPS treatment (1.9±0.1; n=15 vessels) compared to control (3.6±0.2; P<0.05; n=15). In contrast, permeability recovered by day 5 (3±0.1; n=15) and returned to control levels by day 14. Together the data suggest both interendothelial communication and microvessel permeability were continuously modulated during recovery from LPS‐injury. Thus we speculate, changes in Cx43‐dependent interendothelial communication may underlie decrease in microvessel permeability during recovery from LPS‐injury.Grant Funding Source: '' Supported by NIH HL75503''
Impact of Hydroxylase inhibitors on fibrosis associated with IBD (LB789)
Authors: Cabrero Manresa Mario , Tambuwala Murtaza , Cavadas Miguel , Cummins Eoin , Cheong Alex , Taylor Cormac 
Published: June 2021

Fibrosis is a major complication of inflammatory bowel disease (IBD) which cannot be adequately addressed with pharmacologic therapy. In IBD the treatment of fibrosis usually requires surgical resection of colonic segments and is responsible for 75% of surgical interventions in Crohn’s disease (CD). Pharmacological inhibition of hydroxylases ameliorates inflammation in multiple models of IBD. We hypothesized that hydroxylase inhibition may also impact fibrosis in IBD. To test this, the effect of the hydroxylase inhibitor DMOG was tested using an in vivo model of IBD. Mice given 2.5% dextran sodium sulphate (DSS) in drinking water for 5 days and allowed natural recovery for 14 days, developed inflammation and fibrosis, as shown by higher inflammation score, higher submucosal collagen‐I deposition and increased fibroblast infiltration through the colonic mucosa. Mice treated with intra peritoneal DMOG, exhibited less inflammation and lower collagen accumulation, as well as reduced fibroblast infiltration. To test whether this antifibrotic action was secondary to the anti‐inflammatory effect or due to a direct anti fibrotic action, an in vitro model was used. Fibroblasts were treated with TGF‐β1, the key mediator of healing and fibrosis. DMOG was given to the cells prior to TGF‐β1, and α‐smooth muscle actin (α‐SMA) and collagen‐I were analyzed as key fibrosis markers. Both markers were reduced by hydroxylase inhibitors in the presence of TGF‐β1, suggesting a direct antifibrotic action in fibroblasts. Furthermore, this effect was related to a reduced expression of Smad‐3 in human colonic fibroblast, a central effector of the TGF‐β pathway. In conclusion, hydroxylase inhibition reduces fibrosis in vitro and in vivo affecting, at least in part, the TGF‐β pathway. That could be a starting point to search for therapies that can ameliorate fibrosis in this and other diseases.Grant Funding Source: Supported by Science Foundation Ireland
Differential Cardiac Responses to Prolonged Hyperoxia vs. Hypoxia Exposures (LB795)
Authors: Howden Reuben , Heimer Heidi , Cividanes Samantha , Zacherle Emily , Arthur Susan , Bagge Annika , Huet Yvette 
Published: June 2021

Introduction. Pulmonary edema, reduced pulmonary gas exchange and systemic hypoxia can be induced or exacerbated by hyperoxia (high FiO2). Systemic hypoxia or prolonged hyperoxia have both been associated with bradycardia. Hence, hyperoxia‐induced bradycardia, pulmonary edema and systemic hypoxia may be related. The purpose of this study was to assess the contribution of hypoxia to known hyperoxia‐induced bradycardia.Methods. Male C57BL/6J mice (8‐12 wks; 20‐30g; n = 8‐10 per group) were exposed to hyperoxia (100% O2), hypoxia (10% O2) or room air for 55 hours while ECG was recorded. Heart rate (HR), QT‐interval (QTcB) and PR‐interval (PR‐I) responses were calculated from the ECG waveforms.Results. 55hrs hyperoxia induced a substantial reduction in HR and QTcB, compared to baseline (~365bpm HR; ~98ms QTcB; P<0.05), air controls and hypoxia‐exposed mice. Further, an increase in PR‐I, compared to baseline (~19ms; P<0.05), was found in the hyperoxia exposed mice only, to which increases in P‐wave duration contributed the most.Conclusion. This study suggests that if prolonged hyperoxia induces systemic hypoxia, the hypoxia does not contribute to the established hyperoxia‐induced bradycardia.Grant Funding Source: Supported by UNC Charlotte
Does arterial stiffness change under hyperbaric conditions? (LB796)
Authors: Kurtev Angel , Kumar Nakul , Kodali Ahalya , Donnawell Kayla 
Published: June 2021

One of the effects of hyperbaric environment is considered to be peripheral vasoconstriction due to high oxygen tension. It was proposed that this could yield to changes in vascular properties, and to further investigate the issue we examined stiffness index (SI) and reflection index (RI) as calculated from a finger photoplethysmography under normobaric and hyperbaric environment. Eight subjects participated in the study comprising three different conditions spread over one session ‐ breathing air at 1 ATA, breathing air at 2 ATA and breathing 100% oxygen at 2 ATA. Each condition lasted for at least 10 minutes. Photoplethysmography and EKG were continuously recorded using Biopac MP100 multi‐modular system (BIOPAC Systems Inc., Goleta, CA). The compression was done in a multi‐place hyperbaric chamber (Clucas Diving Ltd).The results showed no overall differences in SI and RI when comparing the three conditions. For each subject however there were significant changes in the studied parameters, although in different directions. These findings suggest that SI and RI do change in hyperbaric environment. They also argue that at short exposure and low pressure the vascular effects most probably were not fully developed in order to overcome the inter‐individual differences. Such notion was also supported by the observed stable heart rate in all three conditions and the concomitant small changes in heart rate variability.Grant Funding Source: Saba Ubniversity School of Medicine
Angiotensin II receptor blockade protects against the slow to fast fiber type shift and type I fiber atrophy in the rat soleus with 7 days of hindlimb unloading (LB804)
Authors: Hord Jeffrey , Lee Yang , Lawler John 
Published: June 2021

Reduced mechanical loading during spaceflight and immobilization results in weakening and atrophy of antigravity skeletal muscles. Data indicates that oxidative stress contributes to inactivity‐induced muscle atrophy. Recently we observed that the Nox2 isoform of NADPH oxidase is upregulated during unloading‐induced soleus muscle atrophy. Clues from other tissue types indicate activation of angiotensin II type 1 receptor (AT1R) as an upstream event leading to Nox2 complex formation and activity. Here, we used an AT1R blocker (Losartan) to test the hypothesis that AT1R activation is an upstream signaling event driving Nox2 complex activity, and thus atrophy in the mechanically unloaded soleus. Rats were divided into 4 groups: ambulatory control (CON), ambulatory + Losartan (40 mg/kd/day) (CON‐L), hindlimb unloaded for 7 days (HU), and HU + Losartan (HU‐L). Losartan treatment did not protect against the reduction in soleus mass during 7 days of unloading. However, the increase in Type II muscle fibers seen with unloading was mitigated by Losartan administration. Losartan also protected against atrophy of Type I muscle fibers. In addition, Losartan reduced the signal intensity and membrane localization of the Nox2 subunit p67phox in the unloaded soleus. Our findings suggest a potential role of AT1R activation as an upstream signaling event leading to Nox2 complex formation, activation, and slow to fast fiber‐type shift during mechanical unloading.Grant Funding Source: Supported by NASA (NNX13AE45G), Predoctoral Space Physiology Grant from ACSM/NASA, and the Sydney and J.L. Huffines Institute
Acute lipid administration inhibits amino acid induced phosphorylation of translation repressor 4E‐BP1 in human muscle in an apparent mTOR independent manner (LB813)
Authors: Murton Andrew , Chee Carolyn , Wall Benjamin , van Loon Luc , Tsintzas Kostas , Stephens Francis 
Published: June 2021

At this conference we show that lipid induced insulin resistance is accompanied by impairments in the ability of amino acids (AA) to stimulate muscle protein synthesis in healthy young men, but the mechanism by which this occurs remains unknown. Here we investigated whether the response of mTOR signaling to AA provision is diminished following lipid infusion. 7 male volunteers (23 ± 1 y, 24 ± 1 kg/m2) underwent a 7 h i.v. infusion of either saline or 10% Intralipid (100 ml/h; Fresenius Kabi) on 2 randomised occasions. After 4 h, a 21 g AA bolus was administered intragastrically and the remaining 3 h period performed under euglycaemic (4.5 mmol/L) hyperinsulinemic (50 mU/m2/min) clamp conditions. Key mTOR signaling processes were examined by qPCR and western blot in vastus lateralis biopsies obtained at 4 and 7 h. Irrespective of lipid infusion, hyperinsulinemia and AA feeding resulted in significantly (P<0.05) reduced mRNA levels of two purported suppressors of mTOR activity, REDD1 (saline: 33% and lipid: 50% decline) and KLF15 (saline: 75% and lipid: 74% decline), concomitant to increases in AKT (saline: 93% and lipid: 84% increase; P<0.01) and mTOR (saline: 66% and lipid: 54% increase; P<0.05) phosphorylation. In contrast, lipid infusion blunted the increase of phosphorylation of the downstream translation repressor 4E‐BP1 in response to AA and insulin (saline: 193% (P<0.001) and lipid: 19% increase (NS)). Thus, acute lipid infusion impairs phosphorylation of 4E‐BP1 by AA and insulin in an apparent AKT and mTOR independent manner in healthy young subjects.Grant Funding Source: Supported by a British Nutrition Foundation Drummond Pump Priming Award to A. Murton
Sodium nitrite supplementation improves motor function and skeletal muscle inflammatory profile in old mice (LB817)
Authors: Battson Micah , Gioscia‐Ryan Rachel , Johnson Lawrence , Seals Douglas , Justice Jamie 
Published: June 2021

Aging is associated with motor impairments that reduce quality of life and represent a major healthcare burden, necessitating the development of potential therapies to slow or reverse age‐related functional declines. Chronic low‐grade inflammation develops with advancing age and may be a primary mediator of functional declines. We tested the hypothesis that sodium nitrite (SN) supplementation reverses age‐related motor dysfunction and reduces muscle inflammation.Motor function was assessed using a battery of tests (grip strength [GS], open field distance [OFD] and rota‐rod endurance run [ER]) in young (Y, 3 mo, n=87), old (O, 24 mo, n=40) and old mice treated with SN (ON, n=22, 50 mg/L in drinking water, 8 wk). Function was impaired in O vs. Y (GS: 97.0 ± 18.6 vs. 130 ± 14 g; OFD: 1183 ± 453 vs. 1859 ± 265 cm; ER: 8.4 ± 6.4 vs. 14.4 ± 5.9 min; all p<0.05) and improved with SN (GS: 111 ± 17.0 g; OFD: 1486 ± 485 cm; ER: 14.9 ± 5.1 min, all p<0.05 vs. O).Inflammatory cytokine levels were markedly increased in skeletal muscle of O vs. Y (ELISA: interleukin‐1 β [IL‐1β]: 3.86 ± 2.34 vs. 1.11 ± 0.74; interferon gamma [INFγ]: 8.31 ± 1.59 vs. 3.99 ± 2.59; tumor necrosis factor alpha [TNFα]: 1.69 ± 0.44 vs. 0.76 ± 0.30 pg/mL, all p<0.05), but returned to levels not different than Y with SN (ON: IL‐1β: 0.67 ± 0.95, INFγ: 5.22 ± 2.01, TNFα: 1.21 ± 0.39 pg/mL, all p0.05 vs. Y).Regression models demonstrated that cytokine expression and treatment group (O vs. ON) predicted GS (R2 = 0.822, p<0.001, IL‐1β, INFγ, group), OFD (R2 = 0.574, p<0.01, IL‐1β, group) and ER (R2 = 0.477, p<0.05, INFγ).Our results suggest that SN initiated late in life preserves motor function in old mice, possibly by reducing inflammation in skeletal muscle.Grant Funding Source: Supported by NIH AG013038 and AG000279
Using a chimera to study the role of Galectin‐1 in immunological responses and tumor progression (LB91)
Authors: Bradford Nora , Jin Cho Yong , Bailey Lily , Gustafson Jack , Huang Tianyi , Iyer Hansika , Lu Hancheng , Magliochetti‐Cammarata Tessabella , Nee William , Park Jasmin , Park Jin Young , Sherrin McLean , Sugarman Eli , Tejeda Jeanny , Zhan Bowen , Rokous Judy , Dimitroff Charles 
Published: June 2021

Galectin‐1 (Gal‐1), a protein that impacts the fate and function of immune cells known to fight infection, eliminates cancer, and promotes inflammation, is found in most mammalian tissues at low levels. A small 130 amino acid “jelly‐roll” shaped ß‐galactoside‐binding lectin with a hydrophobic core, Gal‐1 plays a role in controlling intracellular processes, such as cell cycle progression and cell proliferation. Gal‐1 binds with high affinity to glycoconjugates galactose (Gal) and N‐acetylglucosamine (GlcNAc) by van der Waals forces and hydrogen bonding via a highly conserved carbohydrate recognition domain. Because native Gal‐1 oxidizes rapidly and loses its carbohydrate‐binding activity, studying the effect of Gal‐1 has been difficult. The Dimitroff laboratory engineered a Gal‐1 – human immunoglobulin Fc chimeric molecule (Gal‐1hFc), which facilitates dimerization while preventing oxidation‐induced multimerization. Experimental evidence has demonstrated that Gal‐1hFc behaves like native Gal‐1, enabling the use of the chimera to study Gal‐1’s effect on immune responses. The Governor’s Academy SMART (Students Modeling A Research Topic) Team designed a model using 3D printing technology to provide further evidence of Gal‐1hFc’s structure and binding function. Grant Funding Source: Supported by grants from NIH‐CTSA UL1RR031973 and NIH/NCI RO1CA118124
The Silent Assassin (LB93)
Authors: Fuller J. , Kim D. , Arnhold E. , Sung R. , Borden A. , Ortega L. , Johnson R. , Albornoz‐Williams H. , Gummin C. , Martinez A. , Boldt N. , Ogunkunle O. , Ahn P. , Kasten B. , Furumo Q. , Yorke N. , McBride J. , Mullooly I. , Tripi M. , Hutt D. , Klestinski K. , Kaiser C. , Jackson William 
Published: June 2021

According to World Health Organization statistics, the common cold is the most prevalent known disease of humans. The majority of colds are caused by the human rhinovirus‐‐an enterovirus genetically similar to dangerous viruses like polio and hepatitis A. Rhinovirus infection can lead to 72‐hour periods of morbidity, including symptoms like sore throat, runny nose, and muscle weakness, often causing people to miss school or work. Rhinovirus is inert until infection occurs causing the immune system to combat the virus. Rhinovirus transmission is usually via aerosolized respiratory droplets or contact with contaminated surfaces. Once in the body, the virus binds to the cell surface, allowing it to enter cells. Cells use the Intercellular Adhesion Molecule 1 (ICAM‐1) signaling protein to latch on to each other, but viruses bind to ICAM‐1 using a site on the virus surface known as the “canyon.” Since there are over 150 rhinovirus serotypes, it is impossible to put every serotype in one vaccine. Instead, scientists are developing new drugs, such as pleconaril, that bind to the canyon and prevent the virus from attaching to the host cell. This prevents the virus from replicating thus eliminating the spread of the virus and the symptoms caused by it. The Marquette University High School SMART Team modeled a portion of the human rhinovirus capsid bound to pleconaril using 3D printing technology.Grant Funding Source: Supported by a grant from NIH‐CTSA.
Correct Splicing: The Desolation of SMA Spinal Muscular Atrophy and the Survival Motor Neuron Complex (LB94)
Authors: Daley Mary , Erickson Kayla , Griesmer Jessica , Heimermann Megan , Lewandowski Brandy , Loosen Julia , Hoffman Olivia , Rigden Gabrielle , Arnholt Mark , McNally Mark 
Published: June 2021

Spinal muscular atrophy (SMA) is a genetic disorder leading to death before age two. This is caused by degeneration of motor neurons in the spine and affects one in six thousand babies yearly (Families of SMA, 2013). It is unknown why a point mutation or deletion of the SMN1 gene, which produces survival motor neuron (SMN) protein, causes degeneration. The SMN complex is made of SMN and smaller units called Gemin proteins. In a normally functioning system, the SMN1 gene codes for SMN proteins that are part of the SMN complex that forms small nuclear ribonucleoproteins (snRNPs) from SM proteins and sRNA. The SMN protein binds to Gemin‐2 which holds five of the seven SM proteins, smaller units in snRNPs, in place until the target snRNA sequence is located. The final SM proteins are added when the N‐terminus of Gemin‐2 is moved. The snRNPs have many functions in cells, and five of them are involved in RNA splicing. Knowledge available on normal interactions of SMN and Gemin‐2 allow modeling of these proteins to be completed through 3D printing by the Hartford Union SMART (Students Modeling a Research Topic) Team. In children with SMA, the SMN protein cannot to bind to Gemin‐2 because Asp44 is replaced by valine, causing a break in the ionic bond holding the helices together. While this situation still produces normally operating snRNPs, there are too few to correctly splice the pre‐mRNA, leading to SMA.Grant Funding Source: Supported by a grant from NIH‐CTSA.
Anterior Scleritis Manifesting After Coronavirus Disease 2019: A Report of Two Cases
Authors: Feizi Sepehr , Meshksar Aidin , Naderi Ali , Esfandiari Hamed 
Published: June 2021

Purpose:
The purpose of this study was to report 2 patients with anterior scleritis manifesting after coronavirus disease 2019 (COVID-19).

Methods:
The patients with confirmed COVID-19 developed anterior scleritis after their systemic symptoms were markedly improved. A thorough systemic workup identified no underlying autoimmune diseases. Ocular characteristics and safety and efficacy of systemic immunosuppressive therapy were evaluated.

Results:
Case 1 was a 67-year-old woman who presented with necrotizing anterior scleritis in both eyes 3 weeks after the onset of COVID-19. One-week treatment with topical betamethasone and oral prednisolone (65 mg daily) did not result in improvement, so she was started on intravenous cyclophosphamide and subcutaneous adalimumab in addition to oral prednisolone. Necrotizing scleritis was gradually improved over 3 months. Case 2 was a 33-year-old man who presented with sectoral anterior scleritis in his right eye 2 weeks after the onset of COVID-19. He was started on topical betamethasone and oral prednisolone (85 mg daily). One week later, all signs and symptoms disappeared, and topical and oral corticosteroids were gradually tapered off over 2 weeks. There was no recurrence of respiratory symptoms or active scleritis in any cases after discontinuation of treatment.

Conclusions:
These cases suggest that COVID-19 can be associated with anterior scleritis, which responds to immunosuppressive and biologic agents. Ophthalmologists should consider anterior scleritis in patients with COVID-19 who present with ocular pain and redness during the convalescent phase of the illness.