bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of resistance training on systemic inflammatory markers in middle‐aged and older adults
Authors: Barnes Jill Nicole , Cortez‐Cooper Miriam Y. , Anton Maria M. , Tanaka Hirofumi 
Published: June 2021

Systemic inflammation has been implicated in the pathophysiology of cardiovascular disease. There is accumulating evidence that aerobic exercise has a beneficial effect on inflammatory markers. However, it is unclear whether the same is true for resistance exercise. Resistance training is increasingly prescribed for middle‐aged and older adults to improve overall health. Currently, it is not known whether the recommended amount of resistance training is sufficient to reduce systemic inflammation in middle‐aged and older adults. Plasma samples of 27 sedentary but healthy middle‐aged and older adults (aged 54±8 yr) who had undergone 13 weeks of supervised resistance training (10 exercises at ∼70% of 1RM, 3 d/wk) or supervised stretching (attention and time control) were analyzed in this retrospective analysis. The resistance training group increased lean body mass (p<0.01) and maximum strength of the major muscle groups (p<0.05). After 13‐weeks, blood pressure and fasting glucose, cholesterol, and triglycerides did not change. Concentrations of C‐reactive protein, C‐type natriuretic peptide, and tumor necrosis factor‐α were unaltered by either intervention. Our results indicate that the amount of resistance training currently recommended is not sufficient to reduce systemic inflammatory markers in healthy middle‐aged and older adults.Supported by NIH awards AG20966, HL072729
Renin Inhibition Attenuates Ang II Induced Oxidative Stress and Remodeling in the Pancreas of the Ren2 Rat (tg (mREN2)27)
Authors: Habibi Javad , Hayden Melvin R , DeMarco Vincent G , Whaley‐Connell Adam , Schneider Rebecca I , Ferrario Carlos M , Sowers James R 
Published: June 2021

The Ren2 rat expresses the mouse renin gene in numerous extra‐renal sites leading to higher tissue Ang II, oxidative stress, insulin resistance, hypertension, and tissue remodeling. Recently, we showed reversal of oxidative stress, myocardial, renal, and vascular remodeling, and skeletal muscle insulin resistance in the Ren2 after treatment with an AT1R blocker or antioxidant. Here we test whether renin inhibition reverses oxidative stress and remodeling in the pancreas of Ren2. Pancreas was harvested from 9 week old male Ren2 and SD rats following 21 day treatment with 50mg/kg/day aliskiren or placebo. Paraffin sections were incubated with primary antibodies to the NADPH oxidase subunits, NOX2 and Rac1, 3‐nitrotyrosine, complex IV subunit I (mitochondrial marker), and secondary anybodies. Fluorescence of laser confocal images was quantified. VVG stained sections were evaluated for periarterial fibrosis. Signal intensities of Rac1 and 3‐nitrotyrosine, but not NOX2, were elevated in both islets and parenchyma of control Ren2 and aliskiren blunted these changes. Arterial fibrosis found in untreated Ren2 pancreas was prevented by aliskiren. Mitochondrial number, which was higher in control Ren2 pancreas, was lowered by aliskiren. The Ren2 pancreas exhibits oxidative stress and remodeling which are reversed by treatment with aliskiren.Supported by NIH R01‐HL‐63904 and VA Merit (JRS).
Role of the AE3 Chloride/Bicarbonate Exchanger in the Development of Cardiac Hypertrophy
Authors: Sowah Daniel , Alvarez Bernardo , Shull Gary , Casey Joseph 
Published: June 2021

Cardiac hypertrophy is one of the determinants of heart failure, the leading cause of hospitalization in the elderly in Western societies. Several factors contribute to the development of cardiac hypertrophy. Emerging evidence suggest that stimulation of the hypertrophic transport metabolon, a complex involving the Na+/H+ exchanger, NHE1, carbonic anhydrase II and the AE3 Cl−/HCO3− exchanger, plays a key role in the development of hypertrophy. To understand the contribution of AE3 to the hypertrophic cascade, knock‐out mice lacking the gene that encodes AE3 (AE3−/−) were generated. The body weights showed no significant differences between the wild type (AE3+/+), the heterozygous (AE3+/–) and the knock‐out (AE3−/−) littermates. Interestingly, the heart weight to body weight ratio, an index of cardiac hypertrophy, was markedly reduced in the AE3−/− mice (82 ± 2% vs. AE3+/+); the AE3+/− mice were identical to the AE3+/+ mice (102 ± 3% vs. AE3+/+). Phenylephrine (PE), 10 μM, or angiotensin II (ANG II), 1 μM, added 18 h following culturing of adult cardiomyocytes and present for 24 h, increased the cell size of isolated cardiomyocytes of AE3+/+ mice by 20 ± 2% but AE3−/− cardiomyocytes were unresponsive to PE‐ or ANG II‐induced hypertrophy (101 ± 4% vs. AE3+/+). Our data demonstrate that deletion of the AE3 Cl−/HCO3− exchanger gene renders the myocardium significantly less sensitive to cardiomyocyte hypertrophy.Supported by the Heart and Stroke Foundation of Alberta.
Compensatory hyperfiltration and NO in 2k1c and uninephrectomized rats
Authors: Hultström Michael , Helle Frank , Iversen Bjarne M. 
Published: June 2021

Afferent arterioles from the non‐clipped kidney from 2k1c rats has an increased nitric oxide (NO) release after angiotensin II stimulation. This study investigated if this could be compensatory hyperfiltration. Rats underwent uninephrectomy (unx), 2k1c‐ or sham‐surgery. Six weeks after the initial surgery the rats were sacrificed. The effect of L‐NAME on renal blood flow (RBF) was assessed with an ultrasound probe. Af were isolated using the agarose infusion method to study the effect of L‐NAME on Ang‐II induced contraction. NO release was studied using DAF‐FM.RBF was increased in the remnant kidney and in the non‐clipped kidney from 2k1c rats (3.82 ± 0.5 ml/min in controls compared to 8.0 ± 1.61 ml/min in the remnant kidney and 3.2 ± 0.17 and 4.8 ± 0.95 in the clipped and non‐clipped kidney respectively). L‐NAME treatment increased MAP around 30 mmHg in all groups while RBF decreased about 35% in all groups, except in the clipped kidney (−24 ± 3 %). AngII elicited similar contraction in Af from unx and controls. L‐NAME did not alter the contraction. No difference was seen in DAF fluorescence between Af from control and unx following AngII.In conclusion, our results in vivo indicate NO is of lesser importance in the clipped kidney than in the non‐clipped or in control kidneys. Unx Af does not have an increased AngII elicited NO release.The study was funded through Helsevest, Norway.
Downregulation of ENaC expression and activity by Pseudomonas LPS in alveolar epithelial cells
Authors: Dagenais André , Morneau Frédéric , Boncoeur Émilie , Berthiaume Yves 
Published: June 2021

Pseudomonas aeruginosa is a gram negative bacteria that causes chronic infection in cystic fibrosis patients and is known to modulate the epithelial Na channel (ENaC) expression in experimental chronic pneumonia models. For this reason, we tested if LPS from P. aeruginosa could modulate the expression and activity of ENaC in alveolar epithelial cells. Alveolar epithelial cells purified from rat lung were cultured on permeable filters for 4 days before the cells were treated on the apical side with 15 μg/ml of Pseudomonas LPS. The treatment decreased gradually the total transepithelial current with the lowest point reached at 4h with a 35% decline compared to untreated cells. The ENaC (amiloride‐sensitive) portion of this current was declined by 53% at 4h. The α and βENaC mRNA were decreased respectively to 55% and 54% of control by a 4h LPS treatment. Estimation of ENaC activity at the apical membrane following amphotericin B permeabilisation of the basolateral membrane in presence of a Na gradient shows a 52% decrease in 4h LPS treated cells. The decline in ENaC current elicited by LPS is therefore the consequence of a decreased activity of the channel. Ro‐31 8820 a PKC inhibitor abolished the downregulation of ENaC activity in the cells and also restored the α and γENaC mRNA level back to normal. These results show that LPS downregulates ENaC mRNA expression and activity in alveolar epithelial cells by a PKC‐sensitive pathway.Supported by CCFF and CIHR
Delayed lung expansion following pneumonectomy (PNX) improves gas exchange during exercise
Authors: Dane Dan Merrill , Yilmaz Cuneyt , Hsia Connie C.W. , Johnson Robert L 
Published: June 2021

To examine post‐PNX response to expansion of the remaining lung separate from that to other signals (perfusion or inflammation), the right lung of adult male foxhounds was replaced by a custom‐shaped inflated silicone prosthesis filled to end‐expiratory lung volume (EELV) with 50/50 SF6/air. The prosthesis was acutely deflated after 4mo (DEF, n=6) or kept inflated (INF, n=3). Lung volume (mL.kg−1), pulmonary blood flow (Q̇c, mL·(min·kg)−1), lung and membrane diffusing capacities (DLCO and DMCO, mL·[min·mmHg·kg]−1), and pulmonary capillary blood volume (Vc, ml.kg−1) were measured at exercise pre‐PNX and 4 and 12mo post‐PNX. Exercise Q̇c was unaltered. At the same Q̇c (=400), DLCO and DMCO were 25–40% below normal 4mo post‐PNX. By 12mo in INF group, EELV, DLCO and DMCO further declined 28, 10 and 25%, respectively, while in DEF group these values were 87, 32 and 73% higher relative to INF group. Vc changed variably. Mean ± SD. P<0.05 *vs. normal, †vs. INF 4mo, ‡vs. INF 12mo. Thus, delayed lung expansion post‐PNX significantly improved gas exchange at exercise.Supported by NHLBI R01 HL‐040070, 054060, 062873 and 045716.
Teaching the cell based model of coagulation
Authors: Lorr Nancy , Catalfamo James 
Published: June 2021

Coagulation reactions in vivo are localized to cellular surfaces. The endothelial cells that line the vascular space provide a non‐thrombogenic surface preventing unnecessary coagulation, thromboses and platelet activation. When this lining is disrupted, blood comes in contact with the extra vascular tissue exposing platelets to the platelet activating agent collagen. The activated platelet externalizes plasma membrane phosphatidylserines‐which provide a cell anchored scaffolding for formation of coagulation complexes, such as the prothrombinase and tenase complexes, accelerating coagulation reactions 300,000 fold. Activated platelets also form a platelet plug at the site of injury as they aggregate.This laboratory exercise emphasizes the importance of cells in the coagulation process. Coagulation triggered by the “intrinsic” pathway is assayed by addition of inhibitors, Triton‐X, and EGTA to demonstrate the role of phosphatidylserine vesicles, and Ca2+ in the formation of the coagulation complexes. Thrombin conversion of fibrinogen to fibrin, is not inhibited by Triton‐X, demonstrating that the phosphatidylserine coagulation complexes are not required for this final step in the coagulation pathwayThe activation and aggregation of platelets in response to collagen and ADP and their inhibition by prostaglandin E1 is monitored by changes in light transmission as the suspension of platelets undergo activation, first changing shape from disc to sphere and then as they form aggregates of various sizes.
Oxidative Stress Induced by Free Iron Stimulates Phosphatidylcholine Breakdown in Cerebral Cortex Synaptic Endings
Authors: Mateos Melina Valeria , Salvador Gabriela Alejandra , Giusto Norma Maria 
Published: June 2021

Neuronal damage induced by transition metal ions is comparable with the toxic effect of β amyloid peptide. Our purpose was to study the effect of oxidative insult on diacylglycerol (DAG) generation from phosphatidylcholine (PC) in rat cerebral cortex synaptosomes. DAG from PC can be generated by phospholipase D (PLD) and phosphatidic acid phosphatase 2 pathway or by a phosphatidylcholine‐specific phospholipase C (PC‐PLC).Oxidative injury induced by FeSO4 increased DAG generation by 77% with respect to control conditions. Experiments carried out in the presence of ethanol, demonstrated that both PLD and PC‐PLC pathways contributed to DAG generation in the presence of iron. Additionally, free fatty acid generation was inhibited in the presence of Fe2+. Neither the specific phosphoinositide‐3‐kinase inhibitor (LY294002) nor Herbimycin A modified the DAG increase induced by Fe2+. Assays conducted with Fe2+ and either DAG lipase or DAG kinase inhibitors, showed no differences in DAG levels. The phosphoinositide‐PLC inhibitor, U73122, inhibited DAG formation by 23% after 60 min of iron exposure.Our results demonstrate that the generation of lipid messengers through PC breakdown is activated under oxidative injury conditions in synaptic endings.Supported by Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional del Sur and Agencia Nacional de Promoción Científica y Tecnológica.
The complement protein properdin recognizes glycosaminoglycan chains on apoptotic and malignant cell surfaces
Authors: Hourcade Dennis , Mitchell Lynne , Zhang Lijuan , Kemper Claudia 
Published: June 2021

The complement alternative pathway (AP) C3 convertase, a central player of the complement cascade, tags potential targets with C3 fragments that in turn direct lysis and/or clearance and inflammatory reactions. The complement protein properdin has long been known to stabilize the AP convertase. Recently we have found that properdin is also a danger‐recognition molecule: Properdin can bind malignant and apoptotic cells and certain pathogenic microbes. Once bound to a surface, properdin provides a platform for the assembly of the AP C3 convertase, leading to opsonization and clearance and/or lysis. We are interested the mechanism by which properdin can recognize such a variety of potential targets.Properdin is composed of 6 thrombospondin repeats, which in other proteins can harbor glycosaminoglycan (GAG) binding sites. Thus, we investigated the possibility that properdin attaches to mammalian cells via GAGs. Using a panel of wild type and mutant CHO lines, we observed that properdin can bind cells via heparin sulfate and chondroitin sulfate GAG chains associated with cell surface proteoglycans. We then examined properdin interactions with human cells and found that properdin binds GAGs on apoptotic and malignant cell surfaces. Experiments with soluble GAG competitors suggest that properdin harbors multiple GAG‐binding sites that differ in GAG specificity. Supported by NIHR01AI05143.
Elimination of a homologous domain of an intestinal hydrolase enhances trafficking and affects polarized sorting via altered membrane association
Authors: Behrendt Marc , Naim Hassan 
Published: June 2021

The transport‐competent precursor of human intestinal lactase‐phlorizin hydrolase, pro‐LPH, encompasses four homologous domains, whereby the domains III and IV represent the mature brush border enzyme (LPH[beta]). The influence of each of the homologous domains on the structural and functional characteristics of the pro‐LPH polypeptide has been analysed by directed restructuring of the domain composition. Removal of domain IV, which carries the lactase activity, results in accelerated transport kinetics and altered patterns of quaternary structure and membrane association. These novel biosynthetic features of the mutant ([Delta]IV) are directly associated with a retarded dimerization of this mutant in the Golgi and a reduced association with Tween 20‐resistant membranes in the ER. These non‐classical types of membrane microdomains have been shown to be implicated in an early sorting mechanism of membrane proteins. Another mutant that lacks domain III is partially folded and blocked in the ER. Domain III per se is transport competent, enzymatically active and efficiently sorted to the apical surface. Altogether, our data strongly suggest a regulatory role of the membrane associated domain IV in the trafficking of pro‐LPH, while domain III comprises all necessary information for apical sorting.This work has been supported by the German Research Council.
The Integration of the Wnt and cAMP Signalling Pathways by AKAP220
Authors: Logue Jeremy Scott , Scott John D 
Published: June 2021

The cAMP‐responsive protein kinase PKA is a multifunctional enzyme with a broad range of substrates. Proteins designated A‐kinase anchoring proteins (AKAPs) coanchor PKA and substrates together to enhance PKA signalling specificity. Members of this family include MAP2 (microtubule‐associated protein 2), neuronally expressed AKAP79 and AKAP150, and the DNA binding AKAP95. AKAP220 is a less‐well characterized A‐kinase anchoring protein however, is known to anchor protein phosphatase 1 (PP1), PKA, and glycogen synthase kinase‐3 (GSK‐3). Furthermore, I have recently identified β‐catenin as an additional anchored protein. β‐catenin is a transcription factor central to the Wnt signalling pathway. In the absence of Wnt signalling, GSK‐3 can phosphorylate β‐catenin to direct its rapid proteasomal degradation. It has been shown previously by Tanji et al. (2002) JBC, that GSK‐3 anchored to AKAP220 is phosphorylated by PKA and that phosphorylation inactivates GSK‐3. I have shown that the downstream effector of GSK‐3, β‐catenin forms a complex with over expressed AKAP220 in HEK 293 cells. Additionally, endogenous AKAP220 and β‐catenin form a complex in rat H9C2 and PC12 cells. Cellular based assays also suggest that PKA can phosphorylate β‐catenin following stimulation with the adenylyl cyclase activator forskolin. Our recent evidence therefore suggests that AKAP220 may integrate the cAMP and Wnt signalling pathways. The integration of cAMP signalling and the Wnt pathway may play a critical role in processes like wound healing and in pathological conditions like cardiac hypertrophy, of which both pathways have been implicated. The work described will provide fundamental information regarding the integration of these important pathways.*This work is supported by National Institutes of Health grant DK54441.
Small angle x‐ray scattering and analytical ultracentrifugation characterization of the extracellular domain of α‐neurexin, alone and in complex with neuroligin‐1
Authors: Comoletti Davide , Miller Meghan T , Wilson Jennifer , Trewhella Jill , Taylor Palmer 
Published: June 2021

Presynaptic cell adhesion protein α‐neurexin associates with neuroligins, its postsynaptic partner. Polymorphisms of the coding regions of neurexin and neuroligin genes were recently found to be associated with autism spectrum disorders and mental retardation. By small angle x‐ray scattering (SAXS) and analytical ultracentrifugation we have determined the basic structural parameters (maximum dimension, radius of gyration, molecular mass and volume) of the extracellular domain of α‐neurexin. Using the same data, we are now working on the determination their low resolution structure. Gel filtration chromatography and SAXS data suggest that the extracellular domain of α‐neurexin is monomeric in solution. Preliminary binding data on the α‐neurexin/neuroligin‐1 complex suggest a 2:2 stoichiometry where two α‐neurexin molecules bind to a neuroligin‐1 dimer. As mutations of neurexin and neuroligin genes appear linked to autism, these new structural models provide a framework for understanding altered recognition by these proteins in neuro‐developmental disorders.This work was supported by: USPHS Grant R37 GM‐18360 and NIEHS to PT, NAAR #843 and CAN Pilot Research Award to DC; DOE/SC Grant and ARC Federation Fellowship to JT
Angiotensin II modulates vascular smooth muscle cells alpha‐1D‐adrenoceptors
Authors: Gallardo‐Ortíz Itzell , Barajas Maximiliano Ibarra , López‐Sánchez Pedro , Villalobos‐Molina Rafael 
Published: June 2021

Angiotensin II plays an important role in regulating systemic arterial pressure, provokes cardiovascular remodelling and hypertension, as well as an increase in alpha1‐adrenoceptors mRNA and protein. The aim of this work was evaluate the influence of angiotensin II on alpha 1D‐adrenoceptors in isolated smooth muscle cells of Wistar rat aorta. Smooth muscle cells were incubated with angiotensin II (100 nM) for different periods of time (30min–24hrs), and then protein by Westernblot was determined for the alpha 1‐adrenoceptor subtype.The results show an important increment of alpha 1D‐adrenoceptors at 30 min by angiotensin II action, then a time‐dependent diminution in expression of protein at later measurement points. The maximal expression was blocked by losartan and ciclohexymide. This data suggesting that stimulation of AT1 receptors by angiotensin II in isolated cells conduce to increase of alpha 1D‐adrenoceptors and this effect is due to synthesis the novo of alpha 1D‐adrenoceptors, however there is not correlation with longer exposure of animals to the peptide, i.e., hypertension and hypertrophy, and suggest compensatory mechanisms in the animals not observed in isolated cells.Supported by Conacyt 47481, PAPIIT IN203205 and Fundación Miguel Alemán
Retinoids Promote B Lymphopoiesis Even Under Sub‐optimal Conditions
Authors: Chen Xinrong , Kincade Paul W. 
Published: June 2021

We recently found that all trans retinoic acid (ATRA) substantially accelerates progression in the B lymphoid lineage. Spleens of mice treated with ATRA had expanded populations of all major B cell subsets, while progenitor numbers in marrow declined. Retinoids acted directly on progenitors representing multiple stages of differentiation, and with cells from humans as well as from mice. Most of these experiments were done with highly purified progenitors in serum‐free, stromal cell‐free cultures optimized to generate CD19+ cells. Stromal cell co‐culture experiments were then initiated to learn if pDC differentiation was affected. Flt3 ligand (FL) was the only exogenous cytokine added in this circumstance, and we were surprised to find that CD19+B220+ lymphocytes emerged within two to three weeks of culture when 10−7 ATRA was present in the medium. All of the lymphocytes were Rag‐1+Mac1− and a portion were IgM+ B cells. B lymphopoiesis from adult progenitors is normally IL‐7 dependent, so experiments were conducted to determine if this cytokine might be present in our cultures. Indeed, no lymphocytes were generated when the IL‐7 specific M25 antibody was present, or when cultures were initiated with progenitors from IL‐7Rα knockout mice. Preliminary experiments suggest that ATRA slightly increases IL‐7 production in stromal cells, but levels must still be very low. We speculate that signals delivered from retinoid receptors reduce the stringency of those needed for B lymphopoiesis.This work was supported by grants AI20069 and AI58162 from the National Institutes of Health.
Transcriptional regulation of natural IgM secretion by a novel B‐1 cell population in the bone marrow
Authors: CHOI YOUN SOO , BAUMGARTH NICOLE 
Published: June 2021

B‐1 cells are an important source for much of the polyreactive natural antibodies (Ab) that are secreted in the absence of antigenic challenge to protect against pathogens. However, the molecular pathways underlying their differentiation to Ab‐secreting cells are incompletely understood. Contradictory data exist as to whether the transcriptional regulators that control differentiation of conventional B cells to Ab‐generating plasma cells (paired box protein 5a (PAX‐5a), B lymphocyte induced maturation protein 1 (BLIMP‐1), and X‐box binding protein 1 (XBP‐1)) also control B‐1 cell differentiation. Using Ig‐allotype chimeric mice, in which B‐1 cells and their Abs are distinguished from conventional B cells, we identified a novel IgM‐secreting B‐1 cell population in the bone marrow (BM). Together with splenic B‐1 cells, these cells are the major source of natural IgM. While B‐1 cells are abundant in the peritoneal cavity (PerC), there they secrete little IgM. Intracytoplasmic staining and qRT‐PCR analysis of FACS‐purified B‐1 cells from BM, spleen and PerC revealed a clear correlation between high levels of expression for BLIMP‐1, XBP‐1 and sXBP‐1 and the ability of B‐1 cells to secrete IgM. In contrast to conventional B cells, however, B‐1 cells retained high levels of PAX‐5a. The data point to novel regulatory pathways controlling differentiation of natural IgM‐secreting B‐1 cells.This work was supported by NIH/NIAID AI051354.