bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heme Oxygenase‐1 Induction Modulates Hypoxic Pulmonary Vasoconstriction through Upregulation of ecSOD
Authors: Ahmad Mansoor , Kandhi Sharath , Zhao Xiangmin , Kelly Melissa R , Arudra Sri Krishna Chaitanya , Abraham Nader G , Wolin Michael S 
Published: June 2021

Endothelium removed Bovine pulmonary arteries (BPA) contract to hypoxia through a mechanism potentially involving lowering of superoxide‐derived hydrogen peroxide and removal of its basal relaxing effect. Heme oxygenase‐1 (HO‐1) was induced in a 24 hr organ culture of BPA with 0.1mM cobalt chloride to study the effects of HO‐1 on hypoxic pulmonary vasoconstriction (HPV). KCl mediated contraction was not affected, but a catalase reversible attenuation in HPV was observed in HO‐1 induced rings. HO‐1 induced BPA showed a decrease in 5µM lucigenin‐detectable superoxide and an increase in horseradish peroxidase‐luminol detectable peroxide levels. Peroxide scavenging with 0.1mM ebselen increased force development to KCl and partially reversed the decrease in HPV seen on induction of HO‐1. ecSOD expression was increased significantly in HO‐1 induced vessels without any change in intracellular SOD level. Fresh BPA rings treated with Cu,Zn‐SOD showed an attenuation of HPV similar to that seen in HO‐1 induced rings. Thus, HO‐1 induction appears to attenuate HPV in BPA by increasing the conversion of superoxide to peroxide through ecSOD, leading to peroxide levels which may not be adequately lowered by hypoxia.Support by NIH grants HL31069, HL43023 and HL66331.
Interaction during infection by neutrophil bactericide LL‐37 and pharmaceutical antibiotics
Authors: Mehta Pareen , Quinn Tim , Bamberger David , Herndon Betty 
Published: June 2021

The neutrophil (PMN) peptide LL‐37 possesses innate bactericidal activity although diminished bacterial killing by some pharmaceutical antibiotics is reported in the presence of high numbers of PMN. Our earlier studies showed reduced S. aureus penicillin binding protein (PBP) binding when S. aureus was exposed to non‐killing incubation with PMN. This study investigated whether inhibition of pharmaceutical antibiotic bactericidal activity by LL‐37 involves that PBP‐PMN interaction. Rats received intra‐abdominal perforated spheres that were infected with S. aureus after 5‐wk encapsulation. Treatment utilized commercial antibiotics with either PBP‐2 specificity (cefotaxime) or lacking PBP‐2 specificity (cephalexin). Both had similar killing profiles vs. the S. aureus. Control capsules received no commercial antibiotic but had high PMN counts. Abscess fluid was sampled on days 3, 5, and 7 when bacteria and PMN were counted and LL‐37 quantified by Western blot.Over the 7 day treatment time, cephalexin produced a 2.1 ± 1.7 log10 drop in bacterial cfu/mL from day 0, (p=0.029, t‐test). Cefotaxime exhibited only a 0.81 ± 2.5 log10 drop in bacterial cfu/ml from day 0 (p= NS). Day 7 abscess fluid cefotaxime concentration was 1.56 ± 0.99 μg/mL and cephalexin concentration was 1.45 ± 1.1 µg/ml. Both values exceeded the MIC of the infective microbe. Abscess fluid LL‐37 levels correlated negatively with S. aureus counts, showing intra‐capsule bactericide in the presence as well as absence of both antibiotics. These data suggest that the PMN "antibiotic" LL‐37, effective in bactericide in this rat model, appears to function by mechanisms unrelated to the PBP‐2 of the S. aureus cell wall.
Allogeneic hepatocyte transplantation in the rat
Authors: Brückner Sandra , Dollinger Matthias M , Stock Peggy , Hempel Madlen , Ebensing Sabine , Christ Bruno 
Published: June 2021

The immune response leading to rejection of transplanted hepatocytes has not yet been addressed in detail. In the study presented, the rate of hepatic repopulation by transplanted hepatocytes in a syngeneic model (donor: DPPIV +/+ F344; recipient: DPPIV−/− F344) was compared to an allogeneic transplantation model (donor rat: Dark Agouti; recipient rat: DPPIV−/− F344). Wildtype donor hepatocytes delivered via portal injection were detected by histochemical staining of DPPIV enzyme activity in the otherwise negative host liver background and quantified by flow cytometry.24 hours after transplantation, single hepatocytes were detected in the recipient liver parenchyma both in the syngeneic and allogeneic model. 5 days post‐transplantation, small clusters of 1‐5 donor hepatocytes were visible in the syngeneic model as compared to still single cells in the allogeneic model. After 3 weeks, in the syngeneic model 1 % of the recipient liver was replaced by donor hepatocytes while no cells were found in the allogeneic model. Depletion of Kupffer cells (KCs), macrophages resident in the liver, by gadolinium chloride did not increase the rate of repopulation in either model. Thus, KCs mediating the early immune response, were not involved in the rejection of allogeneic hepatocytes, but rather T‐cells eliminating transplanted allogeneic hepatocytes during a three weeks period in time.
Early pregnancy blood gene expression in women destined to deliver preterm
Authors: Enquobahrie Daniel A. , Qiu Chunfang , Muhie Seid , Slentz‐Kesler Kimberley , Williams Michelle A. 
Published: June 2021

ObjectiveWe investigated early pregnancy whole blood global gene expression and risk of preterm delivery (PTD).MethodsRibonucleic acid was extracted from blood samples (collected at 16 weeks gestational age) from 14 women who had a PTD and 16 women who delivered at term. Gene expressions were measured using the GeneChip® Human Genome U133 Plus 2.0 Array. Students T‐test and fold change analysis were used to identify differentially expressed genes. We used cluster and principle components analysis to characterize signature gene expressions. Functions and functional relationships as well as regulatory regions of differentially expressed genes were investigated.ResultsA total of 209 genes, including potential candidate genes (e.g. PTGDS, prostaglandin D2 synthase 21 kDa), were differentially expressed. A set of these genes achieved accurate pre‐diagnostic separation of cases and controls. These genes participate in functions related to immune system, inflammation, tissue development and cell signaling. Promoter sequences for binding sites of putative transcription factors (e.g. EGR1, early growth response 1) were identified.ConclusionMaternal early pregnancy blood gene expression signatures may be useful for PTD risk prediction. Our results provide evidence for better understanding the pathophysiology of PTD; and may yield novel prognostic, preventative and therapeutic opportunities.
Dopamine D2 receptor genotype (C957T) is associated with habitual consumption of sugars in a free‐living population
Authors: Eny Karen M. , Corey Paul , El‐Sohemy Ahmed 
Published: June 2021

Dopamine D2 receptor (DRD2) has been implicated in modulating the rewarding effect of foods high in sugar. The purpose of this study was to determine whether a variation in the DRD2 gene affects habitual consumption of sugars in a free‐living population. Non‐smoking Caucasian men (n=96) and women (n=217) between the ages of 20‐29 years completed a one‐month food frequency questionnaire and were genotyped for the C957T polymorphism in the DRD2 gene. Analysis of covariance with post‐hoc Tukey tests were used to compare nutrient intakes between genotypes, adjusting for potential confounders. Men and women were analyzed separately because of significant interactions between sex and DRD2 genotype. Among men, consumption of sucrose was 60 ± 6, 48 ± 4, and 39 ± 5 g/d for those with the CC, CT and TT genotypes, respectively, with a significant difference between the homozygotes (p=0.04), suggesting an additive mode of inheritance. Among women, sucrose consumption was 42 ± 4, 53 ± 2, and 44 ± 4 g/d for the CC, CT and TT genotypes, respectively, with CC and CT differing significantly (p=0.02). Fructose intake was also different among women with the CC and CT genotypes (p=0.02), suggesting a partial heterosis mode of inheritance. No differences were observed for protein or fat. These findings suggest that genetic variation in DRD2 influences food preference and may explain some of the inter‐individual differences in sugar consumption.Grant Funding SourceAdvanced Foods & Materials Network
Portion size affects hedonic ratings of food in overweight individuals
Authors: Burger Kyle Stanley , Cornier Marc‐Andre , Johnson Susan L. 
Published: June 2021

Increases in portion size result in increased energy intake and likely contribute to the rise in obesity. The underlying mechanism for this 'portion size effect' has not been determined. In our study, participants (n=99; F=57, M=42) of varying body mass index (25.9±7.3) were asked to consume a nutritional supplement, complete visual analog scales for fullness and then rate food images for hedonic value (food appeal & desire to eat) using the computer program ImageRate (scales of 0‐100; 0=lowest & 100=highest). Participants rated 165 food images. Twenty‐three pairs of foods were presented in two portion sizes (large & small). Participants then completed eating behavior questionnaires and height and weight were measured. Food appeal and desire to eat were analyzed for the effects of weight, sex, fullness and interaction terms using analysis of variance. Overweight (OW) participants rated images higher for appeal than lean participants (p<0.05). This result was driven by OW women (p<0.05). Fullness was inversely correlated to appeal and desire to eat (p<0.05). There was a trend for OW participants to rate images of large portions higher than images of small portions for desire to eat (p=0.05). This was significant for OW men (p<0.05). Increased food appeal and desire to eat larger portions suggest possible mechanisms by which larger portion sizes increase energy intake and contribute to excess weight gain.Grant Funding SourceNIDDK DK62874
Inositol 1,4,5‐trisphosphate (IP3) rescued TRPC channel activity from inhibition by phosphatidylinositol 4,5‐bisphosphate (PIP2) in vascular myocytes
Authors: Ju Min , Saleh Sohag , Albert Anthony , Large William 
Published: June 2021

We have previously shown that PIP2 has a marked inhibitory action on TRPC6 channel activity in rabbit mesenteric artery (Albert et al, 2008). Moreover we proposed that diacylglycerol (DAG) is the activating ligand and that DAG and PIP2 act at similar sites on the channel protein to regulate gating of TRPC6. In the present work we studied interactions between DAG, PIP2 and IP3 on TRPC6‐like channel activity in rabbit portal vein myocytes to investigate potential mechanisms involved in mediating previously described synergism between DAG and IP3 (Albert & Large, 2003).Bath application of PIP2 inhibited TRPC6‐like channel activity induced by the DAG analogue, OAG, in inside‐out patches. These data indicate that PIP2 has a similar inhibitory action on TRPC6‐like activity in portal vein as on TRPC6 activity in mesenteric artery. Interestingly, bath application of IP3 in the presence of PIP2 rescued inhibition of OAG‐evoked TRPC6‐like activity in inside‐out patches. Moreover anti‐TRPC6 and ‐TRPC7 antibodies inhibited channel activity suggesting cation channels in portal vein are composed of TRPC6/TRPC7 heterotetrameric structures. These results may indicate that IP3 potentiation of TRPC channel is mediated by TRPC7 proteins.Albert & Large (2003) J Physiol 552, 798‐95; Albert et al (2008) J Physiol 586 3087‐95
Dietary calcium restriction does not exaggerate salt‐sensitive hypertension
Authors: Swenson Christopher D. , Beierwaltes William H. 
Published: June 2021

Dietary Calcium (Ca) has been implicated as an anti‐hypertensive factor, especially in salt‐sensitive hypertension. We hypothesized that decreased dietary Ca would exaggerate salt‐sensitive hypertension in the Dahl Salt‐sensitive (DahlSS) hypertensive rat. Either DahlSS or normal Sprague Dawley (SD) rats (200‐260g bw) were fed a normal sodium (Na) diet (0.22%) with either normal (1.36%) or low (0.15%) Ca content over 3 weeks, then switched to a high Na diet (3.2%) maintaining Ca contents for four more weeks. Systolic blood pressure (SBP) was measured by tail cuff. All rats grew uniformly, regardless of diet. Overall, initial SBP in DahlSS was 163 ± 3 while SD were 128 ± 2 mmHg (p<0.001). Relative changes in SBP are shown in the Table.Overall, SBP in DahlSS rats started higher, and while high Na intake increased SBP in all groups, it increased twice as much in DahlSS over the study period. Ca restriction had no effect in either strain during this time period. Our data do not support the hypothesis that dietary Ca intake exaggerates salt‐sensitive hypertension.Source of Research SupportRO‐1 grant from the NIH; ID# HL076469
Epidermal Growth Factor Inducing Differentiation of Rat Adipose‐Derived Stem Cells into Fibroblast in Vitro
Authors: Jin Huan , Liu Jian , Deng Juan , Ouyang Jingping 
Published: June 2021

ObjectiveTo investigate the induction of EGF(Epidermal growth factor)in the differentiation of rat adipose‐derived stem cells(ADSCs) into fibroblasts in vitro for potential seeding cell of ligament tissue engineering.MethodsAfter inducing and culturing with EGF,ADSCs were determined by the utilization of morphological observation,MTT assay and immunohistochemistry.Results7 or 14 days after induction,the group with EGF developed a more homogeneous fibroblast‐like,spindle‐shaped morphology with long cell processes,and reached higher cell densities.The group with EGF had higher rate in proliferation.10 days after induction.EGF group and control group were positively stained with an antibodies for type I and III collagen,but the staining densities type I and III collagen of the EGF group were higher.The EGF group and the control group were negatively stained with antibodies for type lI collagen.ConclusionThese data suggest that EGF has the capacity to stimulate cell proliferation and expression of extracellular matrix proteins for the tissue engineering of tendons and ligaments.
Adenosine A2a/b receptor‐mediated vasodilation is antagonized by adenosine A1 receptor in coronary circulation of healthy Ossabaw swine
Authors: Neeb Zachary Paul , Long Xin , Mokelke Eric , Edwards Jason , Alloosh Mouhamad , Sturek Michael 
Published: June 2021

Adenosine clearly plays a role in mediating coronary blood flow. However, contributions of specific adenosine receptor subtypes A1, A2a, and A2b (A1R, A2aR, and A2bR) to changes in coronary flow in swine have not been elucidated. Adenosine receptors (AR) are G‐protein coupled, and inhibit (A1R, Gi) or stimulate (A2a/bR, Gs) adenylyl cyclase.HYPOTHESISA1R antagonizes vasodilatory effects of A2a/bR on coronary circulation. The left main coronary artery of Ossabaw miniature swine was accessed with a guiding catheter allowing intracoronary (IC) infusions. Following placement of a flow‐wire into the left anterior descending coronary artery the responses to IC bolus infusions of 0.167, 0.333, 1, and 3 μg/kg adenosine were obtained. Steady‐state infusion of other adenosine receptor agents utilized a small catheter fed over the flow‐wire. Baseline flow was increased by the A2a/bR agonist CV1808 in a dose‐dependent manner, but not changed by other AR subtype‐specific agents. The A2a/bR antagonist DMPX and the A1R‐selective agonist CCPA decreased adenosine‐mediated vasodilation.CONCLUSIONSA1R negatively regulates A2a/bR‐mediated adenosine vasodilation and adenosine is not involved in regulation of basal flow in the coronary circulation of healthy Ossabaw miniature swine.
The effect of mannooligosaccharide supplementation on food intake, body weight and body composition in C57Bl/6 mice
Authors: Smith Daniel Larry , Nagy Tim R. , Wilson Landon S. , Barnes Stephen , Allison David B. 
Published: June 2021

ObjectivePrior research suggests that mannooligosaccharide (MOS or Mannan) supplementation might act as a potential calorie restriction mimetic. This study determined the effect of MOS supplementation on food intake, body weight and body composition in a mouse model.MethodsC57Bl/6 male mice were fed a 45% by calories high fat (HF) "western" type diet with or without 1% MOS (by weight) supplementation (n=24/group) from 10 to 22 weeks of age. Animals were housed individually and provided 95% of ad libitum food intake for the duration of the study. Body weight was measured weekly and body composition (lean and fat mass) measured by QMR noninvasively every 3 weeks.ResultsSupplementation of a HF diet with 1% MOS, consisting of n=4‐13 oligomers by MALDI‐TOF mass spectrometry, tended to reduce total food intake (mean±s.d.; CON: 293.69±10.53g, MOS: 288.10±11.82g; p=0.09) during the study. However, MOS supplementation had no significant effect on final body weight (CON: 25.21±2.31g, MOS: 25.28±1.49g; p=0.91), body weight gain (CON: 5.04±1.49g, MOS: 5.09±0.80g; p=0.90) or total fat (CON: 4.72±0.90g, MOS: 4.82±0.83g; p=0.69).ConclusionIn contrast with previous research, MOS supplementation had no effect on body weight gain or fat accrual during this 12 week study. This research is supported by Purdue‐UAB Botanicals Center for Age‐Related Disease Pilot Grant (P50AT00477) and the UAB CNRU (P30DK56336).
Role of the bradykinin receptor (B2R) in differentiation, migration, and proliferation of endothelial progenitor cells (EPC)
Authors: Bakdash Nadia , Wu Yi , Colman Robert W. 
Published: June 2021

As a potent activator of endothelial cells, bradykinin is known to induce vasodilation, vascular permeability, and nitric oxide production. Bradykinin signaling is initiated by binding to the G protein‐coupled receptor B1R and/or B2R. B2R is constitutively expressed in endothelial cells. Endothelial Progenitor Cells (EPCs) are bone‐marrow derived cells that have the potential to differentiate into mature endothelial cells. We now report that EPCs undergo differentiation, migration, and proliferation without addition of exogenous growth factors. Moreover, EPCs stimulated with bradykinin (250 nM) potentiated differentiation (tube formation), migration, and proliferation by 1.4, 1.6, and 1.7‐fold, respectively. Pre‐incubation of the EPCs with HOE‐140 (1 μM or 10 μM), a B2R selective antagonist, reduced differentiation by 70% (p<0.001), modulated migration by 40% (p<0.001), and inhibited proliferation by 20% (p<0.05), indicating that EPCs utilize the BR2 receptor in these three responses. In addition, we demonstrate that EPCs stimulated with the selective B2R peptidomimetic agonist FR190997 (50 nM) enhanced migration. Furthermore, when pre‐incubated with the B2R antagonist, the migration of EPCs was inhibited by 40% (p<0.05). Thus, we conclude that EPCs utilize the B2 receptor for potentiation of migration, differentiation, and proliferation.NIH 2T32HL007777.
Cellular automaton modeling of biological pattern formation
Authors: Deutsch Andreas 
Published: June 2021

Examples of biological pattern formation are life cycles of bacteria and social amoebae, embryonic tissue formation, wound healing or tumour growth. Thereby, development of a particular spatio‐temporal "multi‐cellular" pattern may be interpreted as cooperative phenomenon emerging from an intricate interplay of local (e.g. by adhesion) and non‐local (e.g. via diffusing signals) cell interactions. Mathematical models are required for the analysis of cooperative phenomena. Typical modeling attempts focus on a macroscopic perspective, i.e. the models (e.g. partial differential equations) describe the spatio‐temporal dynamics of cell concentrations. More recently, cell‐based models have been suggested in which the fate of each individual cell can be tracked. Cellular automata are discrete dynamical systems and may be utilized as cell‐based models. Here, we analyze spatio‐temporal pattern formation in cellular automaton models of interacting discrete cells. In particular, we introduce lattice‐gas cellular automata. In the same spirit as cellular automata, lattice‐gas cellular automaton (LGCA) and lattice Boltzmann (LB) models are promising tools for studying transport and interaction processes in biological systems. In these models the update rule is split into two parts which are called collision (interaction) and propagation, respectively. The collision rule of LGCA can be compared with the update rule for CA in that it assigns new states to each cell based on the states of the sites in a local neighborhood. After the collision step the state of each node is propagated to a neighboring node. This split of the update rule guarantees propagation of quantities while keeping the rules simple. The desired behaviour, e.g. spatio‐temporal pattern formation of a LGCA shows up in the macroscopic limit which can be derived from a theory of statistical mechanics on a lattice. Instead of discrete particles, LB models deal with continuous distribution functions which interact locally and which propagate after "collision" to the next neighbour node. LB models can be interpreted as mean‐field approximations of LGCA. Model applications are bacterial pattern formation and tumour growth.Ref.:A. Deutsch, S. Dormann (2005) Cellular automaton modelling of biological pattern formation, Birkhauser, Boston
PKCalpha‐mediated signaling in regulating adherens junction integrity
Authors: Vandenbroucke Emily Elizabeth , Komarova Yulia , Gao Xiao‐Pei , Vogel Steven , Malik Asrar 
Published: June 2021

The aim of this study was to determine the mechanism of protein kinase C‐α (PKCα)‐mediated disruption of adherens junctions (AJs). We have shown that depletion of PKCα in human microvascular endothelial cells reduces the thrombin‐induced permeability increase by 50%, as assessed by change in transendothelial resistance. PKCα‐depleted endothelial cells formed fewer interendothelial gaps and retained more vascular endothelial (VE)‐cadherin at AJs after thrombin stimulation compared to control cells. VE‐cadherin stability at AJs has been shown to be dependent on p120‐catenin (p120) binding. Dissociation of p120 from VE‐cadherin results in VE‐cadherin internalization and disassembly of AJs. Since activation of PKCα after thrombin stimulation leads to changes in phosphorylation of p120 in endothelial cells, we tested the hypothesis that PKCα‐mediated phosphorylation of p120 causes dissociation of p120 from VE‐cadherin, subsequent disassembly of AJs and increased permeability of the endothelial barrier. Our data demonstrate that thrombin stimulation of endothelial cells results in translocation of PKCα to AJs and interaction with p120. Furthermore, the level of p120 remains unchanged at AJs in PKCα‐depleted cells after thrombin stimulation, supporting our hypothesis that PKCα may induce p120 dissociation from VE‐cadherin, resulting in AJ disassembly.Supported by NIH Grants HL045638 and HL007829