bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuromuscular remodeling and neuromuscular junction instability in human diabetic neuropathy (1168.1)
Authors: Allen Matti , Stashuk Daniel , Doherty Timothy , Kimpinski Kurt , Rice Charles 
Published: June 2021

Diabetic polyneuropathy (DPN) is a progressive axonopathy marked by loss of motor fibers, compensatory collateral reinnervation and reduced stability of neuromuscular transmission. Our objective was to assess the degree of reinnervation and motor unit instability in patients with DPN using decomposition‐based quantitative electromyography (DQEMG). Additionally, relationships between motor unit stability and muscle function were examined. The tibialis anterior (TA) muscle was tested in twelve patients with DPN (65 ± 15 yrs) and 12 age‐matched controls (63 ± 15 yrs). DQEMG was used to analyze surface and intramuscular EMG signals recorded from the TA during moderate voluntary dorsiflexion contractions. Individual motor unit action potential (MUP) trains were identified and analyzed for: MUP size (peak to peak amplitude, area), complexity (turns, fiber dispersion) and stability (near fiber jiggle). DPN patients featured larger (+45% MUP area), more complex (+40% fiber dispersion), and less stable (+30% near fiber jiggle) MUPs (p<0.05). No significant relationships were found between MUP stability and muscular denervation, or strength. MUP complexity and instability were positively related in DPN patients (r=0.46; p<0.05) and controls (r=0.37; p<0.05). DPN is associated with neuromuscular remodeling which leads to increasingly impaired neuromuscular transmission that is detectable using DQEMG.Grant Funding Source: NSERC
Immunohistochemical evidence of nNOS containing fibres in the cardiac ventricle of the rabbit (1169.4)
Authors: Brack Kieran , Saburkina Inga , Rysevaite Kristina , Gukauskiene Ligita , Batten Trevor , Grubb Blair , Pauziene Neringa , Ng G. Andre , Pauza Dainius 
Published: June 2021

Vagal stimulation (VS) is a popular novel therapy in heart failure where its potential in ventricular arrhythmia prophylaxis is highlighted by animal studies showing that VS protects against ventricular fibrillation through nitric oxide (NO). This implies that there are vagal nerves containing neuronal nitric oxide synthase (nNOS) in the ventricle but, anatomical evidence is absent. Our aim was to characterise the phenotype of intrinsic cardiac nerves in the rabbit using immunohistochemistry for tyrosine hydroxylase (TH), choline acetyltransferase (ChAT) and nNOS (n=6). In the atrial and ventricular walls (Figure), TH, ChAT and nNOS positive nerve fibers and cell bodies exist. ChAT and nNOS positive structures predominate in the atria in large and small ganglia. nNOS positive somata and nerve fibers were present within ventricular epi‐ and endo‐cardial nerves, along Purkinje fibers and within the myocardium. The distribution of TH, ChAT and nNOS nerve fibers within epicardial nerve bundles on the anterior (A) and posterior (P) aspects of the left ventricle varied. TH fibres predominate over ChAT and nNOS (TH ‐ 64% (A) 68% (P); ChAT ‐ 10% (A) 8% (P); nNOS ‐ 10% (A) 10% (P)). In summary, we show the first direct evidence of nitrergic nerves within the rabbit intrinisc cardiac nervous system, in particular within the cardiac ventricle, implicating the key role that nitric oxide plays in neurocardiac control.$graphic_71E67ABC‐E99E‐4E1E‐BE16‐51627FC397DE$Grant Funding Source: Supported by Research Council of Lithuania and the British Heart Foundation
Sickle cell transgenic (HbSS) mice lungs produce greater inflammatory mediators with downregulation of dilator proteins (1175.10)
Authors: Bernal Gilberto , Husain Sumair , Opene Micahel , Hillery Cheryl , Belcher John , Ibe Basil 
Published: June 2021

Sickle cell chronic lung disease is one of the notable causes of death in patients with sickle cell disease (SCD). Prevention and treatment of acute chest syndrome (ACS) constitutes a major concern in clinical management of SCD. Some lung complications in SCD result from direct or indirect effect of pulmonary microvascular occlusion by sickle erythrocytes and their adhesion to the vascular endothelium. Vasoactive eicosanoids are released resulting in inflammatory response. Studies with HbSS mice have enhanced knowledge of SCD pathology, but the biochemical mechanisms of initiation and progression of ACS is not well understood. We hypothesized that lungs of SCD patients are under greater inflammatory stress due to decreased expression of anti‐inflammatory proteins and metabolites, but greater inflammatory proteins and metabolites. We studied baseline expression of 5‐Lox, cysLT1 as well as PKA, COX1 and COX2 and CREB and measured Leukotrienes and PGI2 release by lungs of HbSS mice and transgenic HbAA mice. HbSS mice lungs expressed 40‐60% more 5‐Lox and CysLT1, but 40‐70% less COX1/COX2 and CREB proteins; produced 68% greater LTs, but PGI2 was not detected. Expression of PKA was not different. The data suggest that SCD lungs are under greater inflammatory stress which may trigger ACS and sustain sickle cell chronic lung disease in SCD patients.Grant Funding Source: LA Biomed Seed grant 520522
Ca2+ entry via transient receptor potential vanilloid channel 4 mediates ventilation‐induced lung vascular barrier failure (1176.3)
Authors: Michalick Laura , van der Giet Markus , Liedtke Wolfgang , Kuebler Wolfgang 
Published: June 2021

Study objective: High tidal volume ventilation causes lung vascular barrier failure, yet underlying mechanisms are unclear. Here, we tested whether endothelial Ca2+ influx via mechanosensitive TRPV4 may contribute to stretch‐induced pulmonary hyperpermeability in vivo and ex vivo. Next, we probed for the role of putative upstream (serum/glucocorticoid‐regulated kinase (SGK) 1) and downstream (Ca2+‐activated K+ channels) regulators of TRPV4 in this scenario.Methods: Mice were ventilated for 2 h with low (7 ml/kg) and high (20 ml/kg) tidal volumes (LVT/HVT) in vivo. Isolated‐perfused lungs were inflated with 5 or 15 cmH2O (LPIP/HPIP) and [Ca2+]i was quantified by real‐time imaging with or without pharmacological inhibition of SGK1, TRPV4 or Ca2+‐activated K+ channels.Results: TRPV4 deficiency or inhibition by HC‐067047 protected from HVT‐induced lung injury in vivo, and attenuated the endothelial Ca2+ response to HPIP ex vivo. Involvement of SGK1 and Ca2+‐activated K+ channels was evident as reduced lung hyperpermeability in HVT mice following inhibition by GSK650394 (SGK1), apamin or charybdotoxin.Conclusions: Activation of TRPV4 by HVT mediates endothelial Ca2+ influx and promotes lung injury and barrier failure via a signaling pathway that involves both SGK1 and Ca2+‐activated K+ channels, which may present new targets for the prevention or treatment of stretch‐induced vascular pathologies.Grant Funding Source: Supported by an operational grant of the Deutsche Forschungsgemeinschaft to W.M.K.
Hypothyroidism affects dopamine D2 modulation of metabolism, body temperature, and breathing frequency in young female hamsters (1178.1)
Authors: Padilla Tania , Schlenker Evelyn 
Published: June 2021

Previous work from our laboratory showed that administration of 1 mg/kg bromocriptine (B), a D2 receptor agonist, stimulated body temperature, metabolism and ventilation in older hypothyroid females, but depressed these variables in older euthyroid female hamsters without affecting the expression of D2 receptors in various brain regions. This project investigated how hypothyroidism (induced by administration of propylthiouracil in drinking water) affected body temperature, ventilation and metabolism in young euthyroid and hypothyroid female hamsters following administration of vehicle and B. We hypothesized that the physiological responses of 2 month old females to B (1mg/kg) would be similar to those observed in older hypothyroid female hamsters. Results indicated that administration of 1 mg/kg B had little effect on breathing in young euthyroid and hypothyroid female hamsters. A higher dose, 3 mg/kg B, decreased body temperature and frequency of breathing in euthyroid hamsters, but stimulated metabolic rate and caused a post‐hypoxic frequency decline in hypothyroid hamsters. In conclusion, young female hypothyroid hamsters exhibited a lower sensitivity to B and also differences in frequency of breathing, body temperature and metabolic responses to B compared to previous responses observed in older hypothyroid female hamsters.Grant Funding Source: Supported by the UDiscover program at the University of South Dakota and APS STRIDE grant
The obesity epidemic as a result of maternal effects and phenotypic evolution (1179.3)
Authors: Archer Edward 
Published: June 2021

Objective: This research provides a reinterpretation and synthesis of existing evidence for a novel theory of the etiology of the obesity epidemic and the increased prevalence of energy contingent chronic non‐communicable diseases.Theory: Over the past century, socio‐environmental evolution (e.g., decreased pathogenic load, thermoneutral environments, reduced physical labor, and enhanced nutrition) engendered decrements in maternal energy expenditure and metabolic control that increased the availability of energy substrates to the intrauterine milieu. This perturbation of mother‐conceptus energy partitioning resulted in population‐wide cumulative maternal effects and the consequent evolution of human energy metabolism (i.e., intensified fetal insulin production and increments in hyperplastic adiposity). With each successive generation, these anatomic and physiologic alterations led to increments in the competitive dominance of adipocytes over other tissues (e.g., myocytes) in the acquisition and sequestering of nutrient‐energy during post‐prandial periods. By the late 20th century, a metabolic tipping point was reached in which the post‐prandial insulin response was so intense (via enhanced beta‐cell mass and function), and the relative number of adipocytes so magnified, that the sequestering of nutrient‐energy as lipid was inevitable, and obesity unavoidable.
Gd3+ and Gd3+‐containing contrast agents affect human ENaC activity in Xenopus ocytes (1181.14)
Authors: Knoepp Fenja , Clauss Wolfgang , Fronius Martin 
Published: June 2021

In lungs, activity of epithelial sodium‐channel (ENaC) is crucial for regulating the volume and composition of epithelial lining fluid, since dysfunction of this process is associated with diseases, e.g. pulmonary oedema. This study examined a potential impact of Gd3+, a core‐part of nebulized contrast‐agents used for magnetic‐resonance‐imaging (MRI) of lungs, on activity of human ENaC (hENAC). hENaC was expressed in Xenopus laevis oocytes and membrane currents (IM) were recorded by Two‐Electrode‐Voltage‐Clamp measurements.Gd3+ dose‐dependently affected hENaC activity. 0.1mM decreased (17±1 %), whereas 0.5mM induced an increase of IM (27±4 %). Activation by 0.5mM Gd3+ was due to an interference with self‐inhibition (SI) of hENaC (control: 40±3 %; Gd3+: 25±4 %) whereas 0.1mM did not affect SI (control: 32±8 %; Gd3+: 33±7 %). Interestingly, the cysteine modifying compound MTSEA prevented ENaC activation by 0.5mM Gd3+ (the effect by 0.1mM was not affected), whereas histidine‐modifying DEPC prevented inhibition by 0.1mM Gd3+ and did not affect the Gd3+ induced activation. Gd‐DTPA, a Gd3+‐containing contrast agent, showed comparable effects to 0.1mM. These results argue for multiple Gd3+‐binding sites that differentially affect ENaC activity and demonstrate that Gd3+ containing contrast agents can directly interfere with ENaC activity.Grant Funding Source: FK is supported by a scholarship from the university of Giessen
Cell phone based peer counselling can support exclusive breastfeeding: a randomized controlled trial in Kenya (119.5)
Authors: Sellen Daniel , Mbugua Samwel , Webb‐Girard Aimee , Lou Wendy , Duan Wenming , Kamau‐Mbuthia Elizabeth 
Published: June 2021

Objective: To test whether exposure to community‐based continuous cell phone based peer support (CPS) or monthly peer‐led support groups (PSG) increases adoption and duration of exclusive breastfeeding (EBF), as compared to current standard of facility‐based support (Control).Methods: We randomized low‐income women attending antenatal care at a large hospital to receive one of three support strategies from late pregnancy (32‐26 weeks) to 3 months postpartum: CPS, PSG or Control. We compared EBF estimated by maternal 24 h recall of infant foods at 3 months age by intervention group.Results: Participant flow was adequate for power (753 women enrolled, 81% of eligible; 504 infants completed, including twins, 66.6%). Both interventions were associated with a higher proportion of EBF CPS: 90.9%, PSG: 82.8%, Control: 78.2%, p=0.007). Pairwise comparisons of 24 h EBF indicated a significant association of CPS with an 12.7% higher prevalence than Control (90.9 versus 78.2, a 16.2% greater EBF response rate than Control; Chi‐square = 9.8201, p=0.0017) and an 8.1% higher prevalence than PSG (90.9 versus 82.8, a 9.8% greater EBF response rate than PSG; Chi‐square = 4.5768, p=0.0324). Differences could not be attributed to baseline indicators, dropout rates or biases, prevalence and timing of breastfeeding initiation, or EBF prevalence one week after birth. They may be attributed to the frequency of advice.Conclusions: Cell phone based counselling approaches can be at least as effective in supporting EBF as peer support group and facility‐based approaches.Supported by Bill & Melinda Gates Foundation to FHI 360, through the Alive & Thrive Small Grants Program managed by UC Davis; Global Alliance for Improved Nutrition; Canada Research Chair program award.
3‐Methylhistidine and cardiolipin as biomarkers of zinc deficiency (122.3)
Authors: Nkrumah‐Elie Yasmeen , Choi Jaewoo , Kirkwood Jay , Stevens Fred , Tanguay Robert , Chung Carolyn , King Janet , Brown Kenneth , Ho Emily 
Published: June 2021

The global epidemic of zinc deficiency is likely contributing to the development of chronic disorders such as cancer, insulin resistance, and immune dysfunction, though reliable biomarkers for human zinc deficiency are not currently available. To discover novel indicators of zinc deficiency in humans, untargeted metabolomic and lipidomic profiles were assessed from plasma samples collected during a controlled feeding trial in healthy men to induce zinc depletion at baseline (2 wk, 11mg Zn/d), zinc‐depletion (0.6mg Zn/d for 1 wk and 4mg Zn/d for 5 wk), and zinc‐repletion (4 wk, 11mg Zn/d). 3‐methylhistidine, an indicator of human muscle catabolism, was confirmed as the most significantly increased (8‐fold change, P<0.0001) metabolite resulting from zinc depletion, which may indicate endogenous mechanisms for maintaining plasma zinc homeostasis. Lipidomic analysis indicated that dietary zinc deficiency resulted in 5‐fold decreases in sphingomyelin (P=0.039) and phosphatidylcholine (P=0.0298) species, with a 10‐fold increase in cardiolipin (P=0.03766). Elevated levels of cardiolipin and zinc deficiency have both been associated with hyperthyroidism. Thus, this research is significant not only in its identification of clinical biomarkers of zinc deficiency, but may also contribute to unraveling the mechanisms associated with dietary zinc deficiency and health outcomes.Grant Funding Source: Supported by: USANA Health Sciences, T32 ES007060 & P30 ES000210
Food habits of residents who live near corner stores (132.3)
Authors: Young Taylor , Swanson Ann , Craven Tara , Martin Donna , Gibson Cheryl 
Published: June 2021

Background. Working alongside small retail establishments, the Jackson County MO Healthy Corner Store Initiative aims to increase availability of healthy food items in communities with limited healthy food access. Food habit surveys were conducted in neighborhoods surrounding 4 targeted corner stores. Methods. Several strategies were used to distribute the food habit survey within the targeted areas, including mailed surveys, door‐to‐door canvassing, at focus group discussions, and online. Sample size estimates were calculated utilizing census data with consideration of abandoned and vacant households. Survey items included 24 questions about demographic characteristics and food behaviors. Results. A total of 423 food habit surveys were collected. The most important factors participants indicated when deciding where to purchase food were price (32%) and quality of food (26%). About one‐third of participants reported that they consumed only one serving of fruit and two servings of vegetables a day. Major barriers to fruit and vegetable consumption included price (40%) and spoilage time (41%). More than 60% of participants reported purchasing fruit and vegetables at least once a week, with 40% having to travel only 5 to 10 minutes to purchase items. Discussion. Overall, responses to the food habit surveys indicate that individuals are not eating adequate amounts of fruits and vegetables, although the vast majority reported not having to travel far to purchase items. Changing the perception of corner stores by offering a wider variety of low‐cost and high quality foods may enhance healthy food intake among residents.Grant Funding Source: Supported by CDC
Serum C‐peptide is positively associated with the presence of colorectal adenomas (136.7)
Authors: Comstock Sarah , Xu Diana , Hortos Kari , Kovan Bruce , McCaskey Sarah , Pathak Dorothy , Fenton Jenifer 
Published: June 2021

Activation of the insulin ‐‐ insulin‐like growth factor (IGF) signaling axis is hypothesized to increase colon cancer risk. The aim of this study was to determine if serum factors related to insulin or insulin signaling were associated with advanced colon polyps in males. 126 men (48 ‐ 65 yr) were recruited at time of colonoscopy, and blood was collected. Odds ratios were determined using logistic regression for polyp number and polytomous logistic regression for polyp severity. 29% of the men in our study had a tubular adenoma. Participants with C‐peptide levels above 3.3ng/ml were 3.8 (CI: 1.3 ‐ 11.1) times more likely than those with C‐peptide levels less than 1.8ng/ml to have a tubular adenoma. For each category increase in C‐peptide, an individual was 2.0 (CI: 1.2 ‐ 3.4) times more likely to have a tubular adenoma than no polyp. Those individuals with serum soluble receptor for advanced glycation end products (sRAGE) greater than 120.4pg/ml were 0.3 (CI: 0.1 ‐ 0.9) times less likely than those with sRAGE lower than 94.5pg/ml to have 蠅3 polyps than no polyps. For each category increase in sRAGE, an individual was 0.5 (CI: 0.3 ‐ 0.9) times less likely to have 蠅3 polyps than no polyps. Other factors, such as insulin growth factor binding proteins, were not associated with polyp presence or severity in this population. Serum C‐peptide levels are a potential biomarker of polyp severity in white males.Grant Funding Source: Supported by NCI 1R03CA142000 and MSU CTSI
Sulforaphane improves MARCO expression, bacterial clearance and survival in post‐influenza bacterial pneumonia (145.1)
Authors: Kobzik Lester , Wu Muzo , Deloid Glen , Thimmulappa Rajesh , Biswal Shyam 
Published: June 2021

Mechanisms that increase susceptibility for post‐influenza bacterial pneumonia include down‐regulation of the alveolar macrophage (AM) scavenger receptor MARCO by interferon‐γ (IFN‐γ), leading to diminished bacterial clearance. Since MARCO expression can be increased by NRF2 signaling, we tested whether the NRF2‐inducer sulforaphane (SFN) can up‐regulate MARCO expression and improve bacterial clearance after influenza. Human AM‐like monocyte‐derived macrophages (HMDMs) were treated with IFN‐γ (10‐50 IU/ml, 24h) to simulate influenza infection, followed by sulforaphane (SFN, 10µM) for 24h before quantitation of MARCO expression or challenge with green fluorescence protein (GFP)‐expressing S. aureus. Scanning cytometry was used to quantitate MARCO surface labeling and uptake of bacteria. C57/BL6 mice were inoculated i.n. on day 0 with 3500PFU of PR8 influenza virus, and on day 7 with 500 CFU of S. pneumoniae serotype 3. Mice were injected with SFN 25 or 50 mg/kg, or PBS daily from day 6 to 9 after influenza infection. Bacterial clearance was measured on day 1 after S. pneumoniae infection using lung lavage samples. IFN‐γ down‐regulated MARCO expression (p<0.001) of HMDMs and impaired phagocytosis of S. aureus (p<0.001, n=4). SFN added after IFN‐γ significantly improved MARCO expression (p=0.003) and S. aureus phagocytosis (p=0.05), an effect that was inhibited by scavenger receptor blockers poly(I) (p=0.001) or MARCO blocking peptide (P<0.001). In vivo, sulforaphane‐treated mice showed improved bacterial clearance (e.g. 84%, 95% reduction in SFN‐treated mice in 2 trials) and a significantly higher survival rate compared to PBS‐treated mice (75.0% vs. 12.5%, n = 8/grp, p=0.022). Therapeutic targeting of the NRF2 pathway may be beneficial to reduce risk or severity of secondary bacterial pneumonia after influenza.Grant Funding Source: Supported by ES00002
Optimization of the nucleocapsid protein sequences of human measles virus and canine distemper virus to human and canine codon usage bias increases sequence identity and protein expression (145.3)
Authors: Uhl Elizabeth , Osborn Michelle , Michel Frank , Hogan Robert 
Published: June 2021

Amino acids are coded for by two to six different RNA codons and frequency of codon use, known as codon usage bias (CUB), varies between species. Since viruses do not have tRNAs, the translation of viral proteins depends upon utilization of host tRNA, and is impacted by the host’s CUB. We are investigating the importance of codon usage in morbilliviral host adaptation and pathogenicity. Previously we determined that human CUB had significantly higher relative adaptiveness for 6 of 7 CDV proteins than canine CUB. For this study we constructed nucleic acid sequences for HMV and CDV N proteins that were optimized to human and canine CUB. For both viral N proteins, the human and canine codon optimized sequences had increased nucleic acid and codon identity compared to wild type. In addition, codon optimization of the CDV N protein to either the human or canine CUB increased its nucleic acid identity to the wild type (WT) HMV N protein from 66.3% (HMV WT vs CDV WT) to 71.8% (Human CUB vs WT) and 72.2% (Canine CUB vs WT). Finally, protein expression from human and canine CUB optimized HMV and CDV N protein nucleic acid sequences transfected into human (293 HEK) cells was increased over that of the WT constructs. These results indicate that further adaptation of HMV and CDV to the mammalian CUB could potentially enhance viral expression.Grant Funding Source: Supported by Department of Defense Threat Reduction Agency