bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oxidative stress and induction of non‐cardiogenic pulmonary edema following cerebral hypoxia in a canine model
Authors: Khademi Shadi , Jeckel Kimberly , Frye Melinda A , Irwin David , Schroeder Thies , Miller Benjamin F , Monnet Eric , Hamilton Karyn L 
Published: June 2021

Neurogenic pulmonary edema (NPE) is a non‐cardiogenic form of pulmonary edema associated with stroke, traumatic brain injury and seizure. NPE is a public health concern due to high morbidity and mortality, yet the mechanism(s) are unknown.HypothesisCerebral hypoxia, even in the absence of systemic hypoxia, is sufficient to induce pulmonary edema, oxidative stress and compensatory antioxidant mechanisms.MethodsUsing an updated Moss's model, 9 Walker hounds were randomly assigned to cerebral hypoxemia (SaO2 ~55%) with systemic normoxia (SaO2 ~90%) (CH; n=6), or cerebral and systemic normoxia (SaO2 ~90%) (Sham; n=3). Femoral venous (CH) or arterial (Sham) perfusate was delivered from a cardiopulmonary bypass circuit to the brain. Wet to dry lung weight ratios were assessed as an index of pulmonary edema, lipid peroxidation was assessed as an indicator of oxidative stress, and brain and lung compensatory antioxidants were assessed with immunoblotting.ResultsLung wet:dry weight was greater in the CH compared to sham. Lipid peroxidation was greater in CH and was accompanied by increased compensatory antioxidants (hemeoxygenase‐1, NAD(P)H quinone oxidoreductase‐1).ConclusionBrain hypoxemia, despite systemic normoxia, is associated with lipid peroxidation and compensatory antioxidant enzymes, suggesting oxidative stress could contribute to neurogenic pulmonary edema. DARPA N66001‐10‐C‐2134
Gene expression analysis of healthy adults rapidly transported to high altitude
Authors: Herman Nicole Marie , Grill Diane E , Anderson Paul J , Miller Andrew D , O'Malley Kathy A , Johnson Jacob B , Richert Maile L Ceridon , Johnson Bruce D 
Published: June 2021

ObjectiveTo identify novel genes that change expression in healthy adults exposed to hypobaric hypoxia.BackgroundThe uniform and rapid transfer of adults from McMurdo Station (sea level, SL) in Antarctica to the South Pole (2835m, SP) provides a unique opportunity to study the changes in gene expression related to the body's adaptation to high altitude. We hypothesized that a large number of genes would change expression and that many of these genes would be associated with inflammatory processes.MethodsPeripheral venous blood was drawn at SL and after 2 d at SP in 98 subjects (age 37±9 y, 70% male). Peripheral blood mononuclear cells (PBMCs) were isolated and microarray analysis of the mRNA isolated from these cells was performed (Affymetrix HG U133 Plus 2 microarray chip). Analysis and the computation of expression fold changes was performed using the Bioconductor package in R. Pathway analysis was performed using MetaCore™.Results1118 probe sets with significant p‐values (p<0.05) and fold changes were identified and entered into MetaCore™. Several pathways including oxidative phosphorylation, cytoskeletal remodeling, and platelet aggregation were identified as having significant representation in the restricted data set.ConclusionSeveral pathways indicating significantly increased activity in PBMCs were identified. This is indicative of an increased inflammatory response. NSF B‐179‐M.
Prenatal Inflammation (Amnionitis) Impairs Acute Respiratory Response to Hypoxia
Authors: Zenebe Woineshet , Litvin David , Balan Kannan , Martin Richard , Kc Prabha 
Published: June 2021

The brainstem autonomic centers regulating the cardio‐respiratory system in infancy are clearly influenced by perturbations in utero, however, long‐term implications on respiratory centers are unknown. One such common perturbation is inflammation attributed to intra‐ or chorio‐amniotic infection. We hypothesized that prenatal inflammation affects brainstem mechanisms altering long‐term respiratory function. In this study, lipopolysaccharide (LPS, 1 μg/amniotic sac) or normal saline (NS) was microinjected in pregnant Sprague Dawley rats at the 20th day of pregnancy into each amniotic sac and pups were delivered spontaneously. Inflammatory signals in the brainstem as well as hypoxic ventilatory response (HVR) using whole body plethysmography were measured. Our multiplex ELISA and supportive immunohistochemical data showed a highest level of brainstem IL1β and TNF‐α at postnatal day one (p1) which progressively declined (p8 and p15). Physiological data showed baseline respiratory frequency was significantly depressed at p3 (NS=139 ±5 vs LPS=113±5 breaths/min, p<0.05) with no significant difference at p8. HVR to acute hypoxia was significantly depressed at both p8 (NS= 65% ±3 vs LPS=39% ±5 increase above baseline) and p15 (NS= 60 % ±4 vs LPS=27% ±4 increase above baseline). These data suggest that prenatal inflammation alters neural development which may induce long‐term alteration in respiratory response to acute hypoxia. We speculate that suppression of inflammatory signals at an early age may be therapeutic in protecting the respiratory control system.Supported by: NIH R00HL087620
Investigating the effect of temperature on large aggregate conversion of surfactant from ground squirrels
Authors: Cvijanovic Vanja , McCaig Lynda , Staples Jim , Veldhuizen Ruud 
Published: June 2021

During hibernation, ground squirrels’ body temperature is 5°C. Our research focuses on pulmonary surfactant during hibernation. Surfactant is a phospholipid‐rich material which regulates surface tension at the alveolar surface. A change in surface‐area during respiration leads to conversion of the large aggregate form of surfactant to the small aggregate form. Since temperature affects aggregate conversion, we tested the hypothesis that hibernation led to less conversion of large to small aggregates. Lungs of hibernating and summer active ground squirrels were lavaged to obtain large and small aggregates which were measured by a phospholipid‐phosphorous assay. Surface‐area cycling was performed at 37°C and 4°C to determine large aggregate conversion. Total amounts of large aggregate were higher in hibernating squirrels compared to summer active group. The large aggregates from all groups underwent a conversion to a greater extent at 37°C than at 4°C. Changes in large aggregate pool sizes occur during hibernation, in vitro aggregate conversion data suggests this may be as a result of reduced aggregate conversion at low temperatures.Funding: Canadian Institutes for Health Research.
Iloprost suppresses LPS‐induced lung injury and inflammation via Rac1‐dependent mechanism
Authors: Birukov Konstantin G , Wu Tinghuai , Tian Yufeng , Sarich Nicolene 
Published: June 2021

Prostacyclin exhibits protective effects on vascular endothelium and enhances endothelial barrier, as reflected by rapid increase in transendothelial resistance. This study investigated for the first time protective effects of stable prostacyclin analog iloprost using in vitro and in vivo models of lung injury and inflammation induced by bacterial wall lypopolysacharide (LPS). Iloprost attenuated disruption of endothelial monolayer and suppressed activation of inflammatory signaling, including p38 mitogen activated protein kinase, NFkB pathway, Rho signaling, attenuated ICAM1 expression, cytokine release, neutrophil adhesion and migration after LPS challenge. In vivo, iloprost exhibited potent inhibition of LPS‐induced lung injury and vascular leak, as detected by suppression of protein and neutrophil accumulation in bronchoalveolar lavage fluid and reduced myeloperoxidase activation, ICAM‐1 expression, and Evans blue extravasation in the lungs. Inhibition of Rac1 activity using pharmacologic inhibitors or siRNA‐mediated knockdown abolished barrier‐protective and anti‐inflammatory effects of iloprost in vitro and in vivo. We conclude that iloprost‐induced elevation of intracellular cAMP triggers Rac signaling, which attenuates LPS‐induced inflammatory pathways of vascular permeability.Funding: NHLBI HL87823, HL076259, and HL058064
Atypical localization of cytoskeletal and anchoring proteins in the choroid plexus of normal and slc4a10 knockout mice
Authors: Damkier Helle Hasager , Praetorius Jeppe 
Published: June 2021

The cellular distribution of membrane proteins in the choroid plexus (CP) is known to differ from other transporting epithelia. The Na,K‐ATPase is atypically located in the luminal membrane and AQP1 is located in both membranes. Genetic deletion of slc4a10, which encodes the key basolateral Na+ loader Ncbe, is known to decrease the abundance of AQP1 and Na, K ATPase and cause a redistribution of ezrin that anchors certain membrane proteins to the cytoskeleton.The aim of the present study was to determine the distribution of known anchoring proteins and cytoskeletal components in CP of normal and NCBE knockout mice by immunohistochemical analysis.A known binding partner of AQP1, β‐catenin, was located only near the basolateral membrane and was less abundant in the NCBE knockout mouse. Ankyrin 3, a known Na,K ATPase anchor in CP was localized near the luminal membrane, but was less abundant in the NCBE knockout mouse. Spectrin cytoskeleton was localized close to the luminal membrane and is known to bind to Ankyrin 3. In the NCBE knockout mouse, spectrin labelling was observed in both membrane domains, however, but predominantly basolaterally.In conclusion, AQP1 in the luminal membrane of CP is not anchored to β‐catenin. Furthermore, the removal of the key Na+ loader, NCBE, causes not only a decrease in abundance of the Na, K ATPase binding partner Ankyrin 3, but also a redistribution of the spectrin‐cytoskeleton.
Human cortical bone maintenance: does mechanical loading compensate for bone loss associated with metabolic stress?
Authors: Eleazer Courtney D. 
Published: June 2021

Cortical bone adapts to environmental factors at macroscopic and microscopic levels by altering mass and shape, and thus strength. As few studies have focused on how these factors interact in humans, researchers continue to investigate mechanical and metabolic influences on bone as if they act independently. This study utilizes an archaeological human juvenile sample from a medieval Lithuanian cemetery. Juvenile bone is favored over adult bone because it responds strongly to both mechanical and metabolic effects. Macroscopic and microscopic bone morphology were assessed in three skeletal elements under different levels of mechanical loading (i.e., femora, humeri, ribs) and compared among individuals under varying amounts of metabolic stress. Analyses evaluated whether, in the presence of bone loss due to metabolic stress, bone mass and strength were preferentially maintained in bones under the highest mechanical demands. Results indicate that such a preferential maintenance may occur, suggesting that systemic metabolic bone loss is compensated by high local loading demands. Results caution researchers against evoking solely mechanical or metabolic causes for variation in cortical bone morphology.Grant Funding Source: NA
DNA intercalation impacts multiple steps in the recognition of damaged bases by a DNA glycosylase
Authors: Hendershot Jenna , O'Brien Patrick 
Published: June 2021

To repair DNA, enzymes must overcome the problem of gaining access to bases that are normally embedded in the duplex. One solution to this problem is base flipping, the 180° rotation of a damaged base into an enzyme active site. Base flipping is ubiquitous for repair enzymes, but the mechanism is poorly understood. A dissection of the reaction mechanism will shed light on how repair enzymes can search the genome effectively to locate sites of DNA damage. Human alkyladenine DNA glycosylase (AAG) is a monomeric protein responsible for removing a diverse set of alkylated and oxidized purine bases. The crystal structure of AAG revealed the DNA is bent and a tyrosine (Y162) intercalates into the space left by the flipped‐out damaged nucleotide. In this study we have mutated this residue to smaller (Y162A) and larger (Y162W) amino acids and characterized the kinetic mechanism of these mutants using the naturally fluorescent 1,N6‐ethenoadenosine (εA) lesion. The Y162W mutant has robust glycosylase activity toward εA and the stably paired lesion hypoxanthine (Hx). Using stopped‐flow experiments, the binding of Y162W to εA‐DNA was measured monitoring both tryptophan fluorescence and εA fluorescence. Overall, the kinetic parameters for Y162W are almost identical to wild‐type AAG. In comparison, Y162A flips bases 60‐fold faster than wild‐type. This unexpected finding suggests Y162 in wild‐type acts as a selectivity filter and slows base flipping. The Y162A mutant also unflips very rapidly, so the overall equilibrium constant for base flipping is decreased by 300‐fold.Supported by: Cellular Biotechnology Training Grant
ARHGEF3.2 modulates Wnt‐PCP signaling in dorsal marginal zone of Xenopus embryos during early development
Authors: Yoon Jaeho , Heo Jee‐In , Kim Sung Chan , Park Jae‐Bong , Lee Jae‐Yong , Kim Jaebong 
Published: June 2021

Rho guanine nucleotide exchange factor (RhoGEF) regulates various cellular processes including cell polarity, cytokinesis, and cell movements via activating small GTPase such as RhoA, Rac1 and CDC42. During gastrulation of Xenopus embryos, noncanonical Wnt signaling is the major signal pathway to regulate convergent and extension cell movements in DMZ region. In previous publications, activin induces dorsal mesoderm and noncanonical Wnt signaling is highly activated in dorsal mesoderm to promote cell movements. Although about 70 GEF distinct GEF homologues have been studied in humans, few GEFs of Xenopus are only identified and explored for its function during early embryogenesis.In this study, we showed that EST gene (assesion No. XL.3374), which has been named xARHGEF3.2 was induced by activin treatment in ectodermal explants and expressed at dorsal marginal region in gastrula embryo. It was constructed to explore the role of xARHGEF3.2 during gastrulation. Over‐expression / knockdown of ARHGEF3.2 caused gastrulation defects. Furthermore, Biochemical analysis showed that xARHGEF3.2 activated RhoA through interaction with Dishevelled and Daam‐1.Taken together, our results suggest that xARHGEF3.2 is induced by activin signaling and modulates convergent and extension cell movement via Wnt‐PCP signaling during the early Xenopus embryos development
Closing the conceptual gap between self‐perception and reality in obesity prevention
Authors: Song Hee‐Jung , Grutzmacher Stephanie K 
Published: June 2021

ObjectiveThe self‐perception of caloric intake and a healthy diet is an important indicator for lifestyle modification. The conceptual gap between the self‐perception and objective status attenuates the effectiveness of health programs. The purpose of this study is to present the conceptual gap between self‐perception and objective status to clarify problems and corresponding intervention strategies.DesignCross‐sectional study. 30–60 minute in‐person interviews (n=151) were conducted.Setting11 Supplemental Nutrition Assistance Program (SNAP) regional offices located in five counties in MarylandSubjectsA convenience sample of 151 SNAP eligible adultsResultsParticipants’ perceived adequacy of caloric intake was inconsistent with their weight status showing a significant conceptual gap. 65.1% had BMI ≥ 25, but only 40.8% perceived that their caloric intake is “too high” and 36.4% reported they have a weight problem. Also, a majority of people (range 67.1 – 96%) perceived that it is important to follow a healthy diet, but only 37.1% had adequate health literacy, implying that their perception could not be supported by their literacy level.ConclusionsBroad consensus about the importance of following dietary guidelines has been established in the low‐income, SNAP eligible population, but significant conceptual and literacy gaps exist for translation. Exploring whether these gaps result from insufficient health literacy or a lack of internalization process is needed for future intervention strategies.
Agriculture, Income and Nutrition Linkages in India: Findings from a Nationally Representative Survey
Authors: Kadiyala Suneetha , Bhagowalia Priya , Headey Derek 
Published: June 2021

In India, the glacial reduction in the prevalence of undernutrition in the face of strong economic growth has raised the possibility that undernutrition is disconnected from economic growth in general and perhaps from agricultural growth in particular.We utilize India Human and Development Survey (IHDS), a nationally representative survey covering 41,554 households in rura and urban areas. Using Ordinary Least Squares and Instrumental Variable regression techniques, we test if agricultural income, irrigation and land ownership determine agricultural production patterns, household dietary diversity and child anthropometry.The income gradient for undernutrition is very weak, with only the richest quintile showing 0.5 HAZ gradient compared the poorest (p<0.001). Economic status and land ownership are negatively correlated with the budget shares of cereals, pulses and vegetables and positively correlated with milk. Irrigation and crop diversity predict household diet diversity, but neither the household dietary diversity score nor the food group budget shares significantly explain HAZ or WHZ. Access to safe water and sanitation, antenatal check‐ups and vaccinations predict child anthropometry.Agricultural programs aimed at irrigation, crop and livestock diversification along with direct nutrion and health interventions can improve nutrition outcomes in India.
A label‐free photonic crystal biosensor for the assessment of iron status using ferritin
Authors: Peterson Ross David , Cunningham Brian , Andrade Juan , Engeseth Nicki 
Published: June 2021

Identification of populations at risk of iron deficiency is of critical concern. We present an application of photonic crystal (PC) biosensors as a diagnostic test for ferritin, a biomarker for iron deficiency. PCs are periodic dielectric surface structures designed to reflect a narrow band of wavelengths when illuminated by a broadband light source. Adsorption of biomolecules causes the reflected wavelength to shift to greater values, providing a simple mechanism for label‐free detection using available detection instruments. PC surface was functionalized with silane for immobilization of primary ferritin antibodies, followed by a blocking step to inactivate remnant silane binding sites. Sensitivity was tested using serial dilutions of human liver ferritin (450 kDa) from 5.0 to 0.15 μg/ml; and a secondary antibody to amplify initial signal. Specificity of the assay was verified by evaluating biosensor binding to BSA. The PC sensor gave a concentration‐dependent response for ferritin (R2= 0.986). When compared to commercial ELISA kit, ferritin response provided comparable limits of detection. Antibodies showed high specificity to ferritin. A 40‐minute assay protocol for label‐free detection of ferritin provided dose‐dependent response in the physiologically relevant concentration range for ferritin in serum; a step towards a simple point‐of‐care assay for iron deficiency diagnosis.Grant Funding Source: College of ACES DNS 20/20
A prudent diet attenuates lung function decline in cigarette smokers
Authors: Tang Wenbo , Guertin KA , Arnold KB , Hartline JA , Minasian LM , Lippman SM , Klein E , Cassano PA 
Published: June 2021

BackgroundMost previous studies of diet and lung function focus on individual nutrients and/or foods. Dietary pattern analysis is a strong alternative approach, but very few studies examine the dietary pattern—lung function decline association.MethodsThe association between dietary patterns and decline of forced expiratory volume in 1 s (FEV1) was investigated in 2,560 male adults. Dietary patterns were derived from food frequency data using principal component analysis, and linear mixed‐effects models examined these patterns with FEV1 decline over ~3 years, adjusting for confounders. Given the importance of smoking, dietary pattern × smoking interactions were tested.ResultsA more prudent pattern (higher intake of fruits, vegetables and whole grains) was associated with a slower decline in FEV1 in smokers only (top vs. bottom tertile of pattern: +37.8 mL/y; trend Pinteraction = 0.0008). A more Western pattern (higher intake of meat, potatoes and snacks) was associated with a lower FEV1 at study baseline (top vs. bottom quintile: −162.4 mL; P for trend = 0.001), but not with FEV1 decline either overall or by smoking.ConclusionsIn males, a prudent dietary pattern was associated with a slower decline in lung function in smokers only, and a Western dietary pattern was associated with lower levels of lung function, but not change over time.Grant Funding Source: NHLBI R01HL071022 (PAC), and, in part, NCI/DCP CA37429, NCCAM.
Fathers’ acceptance of videoconferencing for remote lactation consultation: a pilot study
Authors: Lewis Daniel Gregory , Habibi Mona F , Kavanagh Katherine F 
Published: June 2021

The objective was to pilot a survey designed to assess fathers’ perceived acceptability of videoconferencing technology for the purpose of remote lactation consultation (RLC) for their partners. Data were obtained via a voluntary web‐based survey advertised on social media websites. Fathers >; 18 years old, with an infant < 6 months of age who was receiving breast milk at the time of study participation were eligible. Forty‐one fathers were eligible, consented, and completed the survey. Fathers were asked about their comfort with their partners’ use of web‐based communication software, general comfort levels with their partners’ breastfeeding, about any breastfeeding problems encountered, and any subsequent actions taken to correct these problems. Comfort with using web‐based communication software was generally high, with 81% (n=33) of fathers reporting comfort with their partners using email or instant messaging to communicate with health professionals, and 84% (n=35) reporting that they would feel comfortable with partners using web‐cams to communicate with health professionals. Of those reporting partners experiencing breastfeeding problems, 74% (n=30) of these problems would be included within the scope of practice of an International Board Certified Lactation Consultant. Results of this pilot study indicate acceptance among fathers of videoconferencing for the purpose of RLC.Grant Funding Source: University of Tennessee Internal Seed Funds