bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Analysis of the Protein Shell of the Microcompartments Involved in Coenzyme B12-Dependent 1,2-Propanediol Degradation bySalmonella
Authors: Cheng Shouqiang , Sinha Sharmistha , Fan Chenguang , Liu Yu , Bobik Thomas A.
Published: January 2011

Hundreds of bacterial species use microcompartments (MCPs) to optimize metabolic pathways that have toxic or volatile intermediates. MCPs consist of a protein shell encapsulating specific metabolic enzymes. InSalmonella, an MCP is used for 1,2-propanediol utilization (Pdu MCP). The shell of this MCP is composed of eight different types of polypeptides, but their specific functions are uncertain. Here, we individually deleted the eight genes encoding the shell proteins of the Pdu MCP. The effects of each mutation on 1,2-PD degradation and MCP structure were determined by electron microscopy and growth studies. Deletion of thepduBB′,pduJ, orpduNgene severely impaired MCP formation, and the observed defects were consistent with roles as facet, edge, or vertex protein, respectively. Metabolite measurements showed thatpduA,pduBB′,pduJ, orpduNdeletion mutants accumulated propionaldehyde to toxic levels during 1,2-PD catabolism, indicating that the integrity of the shell was disrupted. Deletion of thepduK,pduT, orpduUgene did not substantially affect MCP structure or propionaldehyde accumulation, suggesting they are nonessential to MCP formation. However, thepduUorpduTdeletion mutants grew more slowly than the wild type on 1,2-PD at saturating B12, indicating that they are needed for maximal activity of the 1,2-PD degradative enzymes encased within the MCP shell. Considering recent crystallography studies, this suggests that PduT and PduU may mediate the transport of enzyme substrates/cofactors across the MCP shell. Interestingly, apduKdeletion caused MCP aggregation, suggesting a role in the spatial organization of MCP within the cytoplasm or perhaps in segregation at cell division.
Tectonic significance of the Carboniferous Big Pond Basin, Cape Breton Island, Nova Scotia
Authors: Bradley Dwight C. , Bradley Lauren M.
Published: January 2011

Detailed mapping in southeastern Cape Breton Island has revealed a strike-slip origin for the small Carboniferous outlier at Big Pond. Topographically low Carboniferous sedimentary rocks occur between splays of a previously unrecognized, northeast-trending set of high-angle faults, the Big Pond fault system. The section is dominated by fanglomerates, which coarsen toward the faulted basin margins and which were deposited and (or) reworked by currents flowing toward the basin's center and along its axis. We interpret the fanglomerates as syntectonic. Interbedded limestones of Visean age (Windsor B Subzone) provide age control for the upper part of the 300 m section and, by inference, for at least some of the fault motion. Dextral motion on the Big Pond fault system is indicated by (1) slickenside stepping directions on minor faults, which juxtapose basement against basement and which parallel the main northeast-striking fault; (2) northeast-striking mesoscale faults within the basin, which produce dextral offsets; and (3) shear and extension fractures in fanglomerate clasts along the northeast-striking basin margin faults, which reveal dextral and down-to-basin motion. The location of the basin at a right step in the through-going dextral fault system implies that it is a pull-apart basin. We suggest that during Visean times, southern Cape Breton Island was cut by several such dextral wrench faults and associated sedimentary basins and that the tectonic climate was similar to that recognized by previous workers in Newfoundland and New Brunswick. No evidence was found in support of the paleomagnetically based hypothesis for sinistral strike slip during this time.
Discovery of Triassic phylloid algae: possible links with the Paleozoic
Authors: Reid R. Pamela
Published: January 2011

Triassic phylloid algae have recently been discovered in a reef in the southern Yukon. These plate-like algae are the primary frame builders in a few small patches in the upper section of the reef, where they are associated with fossils and sedimentary structures suggesting deposition in very shallow water. A vague, porous microstructure in some of the algae suggests affinities with Paleozoic codiacean phylloid algae, but preservation is too poor to permit definite classification. Nevertheless, the indication that phylloid algae did not become extinct at the end of the Paleozoic, as formerly supposed, increases the possibility of finding missing evolutionary links between Paleozoic phylloid algae and their modern counterparts.
DOES ENTROPIC GRAVITY BOUND THE MASSES OF THE PHOTON AND GRAVITON?
Authors: MUREIKA J. R. , MANN R. B.
Published: January 2011

If the information transfer between test particle and holographic screen in entropic gravity respects both the uncertainty principle and causality, a lower limit on the number of bits in the universe relative to its mass may be derived. Furthermore, these limits indicate particles that putatively travel at the speed of light — the photon and/or graviton — have a nonzero mass m ≥10-68 kg . This result is found to be in excellent agreement with current experimental mass bounds on the graviton and photon, suggesting that entropic gravity may be the result of a (recent) softly-broken local symmetry. Stronger bounds emerge from consideration of ultradense matter such as neutron stars, yielding limits of m ≥10-48–10-50 kg , barely within the experimental photon range and outside that of the graviton. We find that for black holes these criteria cannot be satisfied, and suggest some possible implications of this result.
SHARP DECAY ESTIMATES OF THE SOLUTIONS TO A CLASS OF NONLINEAR SECOND ORDER ODE's
Authors: HARAUX ALAIN
Published: January 2011

We establish the rate of decay to 0 and we study the oscillation properties of solutions to the scalar second order ODE: u″ + c|u′|αu′ + |u|βu = 0, where c, α, β are positive constants. Various extensions (forced equation, system) are considered.
Blood flow dynamics of one cardiac cycle and relationship to mechanotransduction and trabeculation during heart looping
Authors: Garita Barbara , Jenkins Michael W. , Han Mingda , Zhou Chao , VanAuker Michael , Rollins Andrew M. , Watanabe Michiko , Fujimoto J. G. , Linask Kersti K.
Published: January 2011

Analyses of form-function relationships during heart looping are directly related to technological advances. Recent advances in four-dimensional optical coherence tomography (OCT) permit observations of cardiac dynamics at high-speed acquisition rates and high resolution. Real-time observation of the avian stage 13 looping heart reveals that interactions between the endocardial and myocardial compartments are more complex than previously depicted. Here we applied four-dimensional OCT to elucidate the relationships of the endocardium, myocardium, and cardiac jelly compartments in a single cardiac cycle during looping. Six cardiac levels along the longitudinal heart tube were each analyzed at 15 time points from diastole to systole. Using image analyses, the organization of mechanotransducing molecules, fibronectin, tenascin C, α-tubulin, and nonmuscle myosin II was correlated with specific cardiac regions defined by OCT data. Optical coherence microscopy helped to visualize details of cardiac architectural development in the embryonic mouse heart. Throughout the cardiac cycle, the endocardium was consistently oriented between the midline of the ventral floor of the foregut and the outer curvature of the myocardial wall, with multiple endocardial folds allowing high-volume capacities during filling. The cardiac area fractional shortening is much higher than previously published. The in vivo profile captured by OCT revealed an interaction of the looping heart with the extra-embryonic splanchnopleural membrane providing outside-in information. In summary, the combined dynamic and imaging data show the developing structural capacity to accommodate increasing flow and the mechanotransducing networks that organize to effectively facilitate formation of the trabeculated four-chambered heart.
20-Hydroxyeicosatetraenoic acid synthesis is increased in human neutrophils and platelets by angiotensin II and endothelin-1
Authors: Tsai I. J. , Croft K. D. , Puddey I. B. , Beilin L. J. , Barden A.
Published: January 2011

The cytochrome P-450 arachidonic acid metabolite 20-HETE is central to the regulation of vascular tone, renal function, and blood pressure and is synthesized in the rat kidney in response to angiotensin II (ANG II) and endothelin-1 (ET-1). There are very few studies examining the cellular synthesis of 20-HETE in humans. We aimed to measure human neutrophil and platelet 20-HETE levels under basal conditions and after ANG II, ET-1, and calcium ionophore (CaI). 20-HETE was measured in human platelets and neutrophils after saline (control), CaI (2.5 μg/ml), and ANG II or ET-1 (10 nmol/l-1 μmol/l) incubations. The effect of cells, which were preincubated with the ω-hydroxylase inhibitor N-hydroxy- N′-(4- butyl-2-methylphenyl) (HET0016, 10 nM), ANG II types 1 or 2 (AT1or AT2) receptor inhibition with irbesartan (1 μmol/l) or PD-123319 (1 μmol/l), or endothelin receptor subtypes A or B (ETAor ETB) receptor inhibition with BQ-123 or BQ-778 (100 nmol/l), was studied. Neutrophil and platelet content and release of 20-HETE was significantly increased by CaI and blocked by the ω-hydroxylase inhibitor HET0016. ANG II and ET-1 significantly increased neutrophil and platelet content and release of 20-HETE. ANG II increased 20-HETE via the AT2receptor. ET-1 increased 20-HETE through the ETBreceptor in platelets and both the ETAand ETBreceptors in neutrophils. These studies show that human platelets and neutrophils synthesize 20-HETE in response to ANG II and ET-1. 20-HETE synthesis in both cell types was predominantly mediated via the AT2and ETBreceptors. Stimulation via these receptor pathways has generally been thought to be cardioprotective and requires further studies in clinical situations associated with low-grade inflammation or where ANG II and ET-1 are elevated to clarify the role of 20-HETE.
Nicotine aggravates the brain postischemic inflammatory response
Authors: Bradford Shayna T. , Stamatovic Svetlana M. , Dondeti Raj S. , Keep Richard F. , Andjelkovic Anuska V.
Published: January 2011

A substantial body of evidence suggests that nicotine adversely affects cerebral blood flow and the blood-brain barrier and is a risk factor for stroke. The present study investigated the effect of nicotine on cerebrovascular endothelium under basal and ischemia/reperfusion injury under in vivo condition. Nicotine (2 mg/kg sc) was administered to mice over 14 days, which resulted in plasma nicotine levels of ∼100 ng/ml, reflecting plasma concentrations in average to heavy smokers. An analysis of the phenotype of isolated brain microvessels after nicotine exposure indicated higher expression of inflammatory mediators, cytokines (IL-1β, TNF-α, and IL-18), chemokines (CCL2 and CX3CL1), and adhesion molecules (ICAM-1, VCAM-1, and P-selectins), and this was accompanied by enhanced leukocyte infiltration into brain during ischemia/reperfusion ( P < 0.01). Nicotine had a profound effect on ischemia/reperfusion injury; i.e., increased brain infarct size ( P < 0.01), worse neurological deficits, and a higher mortality rate. These experiments illuminate, for the first time, how nicotine regulates brain endothelial cell phenotype and postischemic inflammatory response at the brain-vascular interface.
[Ca2+]isignaling vs. eNOS expression as determinants of NO output in uterine artery endothelium: relative roles in pregnancy adaptation and reversal by VEGF165
Authors: Yi Fu-Xian , Boeldt Derek S. , Magness Ronald R. , Bird Ian M.
Published: January 2011

Pregnancy is a time of greatly increased uterine blood flow to meet the needs of the growing fetus. Increased uterine blood flow is also observed in the follicular phase of the ovarian cycle. Simultaneous fura-2 and 4,5-diaminofluoresceine (DAF-2) imaging reveals that cells of the uterine artery endothelium (UA Endo) from follicular phase ewes produce marginally more nitric oxide (NO) in response to ATP than those from luteal phase. However, this is paralleled by changes in NO in response to ionomycin, suggesting this is solely due to higher levels of endothelial nitric oxide synthase (eNOS) protein in the follicular phase. In contrast, UA Endo from pregnant ewes (P-UA Endo) produces substantially more NO (4.62-fold initial maximum rate, 2.56-fold overall NO production) in response to ATP, beyond that attributed to eNOS levels alone (2.07-fold initial maximum rate, 1.93-fold overall with ionomycin). The ATP-stimulated intracellular free calcium concentration ([Ca2+]i) response in individual cells of P-UA Endo comprises an initial peak followed by transient [Ca2+]ibursts that are limited in the luteal phase, not altered in the follicular phase, but are sustained in pregnancy and observed in more cells. Thus pregnancy adaptation of UA Endo NO output occurs beyond the level of eNOS expression and likely through associated [Ca2+]icell signaling changes. Preeclampsia is a condition of a lack of UA Endo adaptation and poor NO production/vasodilation and is associated with elevated placental VEGF165. While treatment of luteal NP-UA Endo and P-UA Endo with VEGF165acutely stimulates a very modest [Ca2+]iand NO response, subsequent stimulation of the same vessel with ATP results in a blunted [Ca2+]iand an associated NO response, with P-UA Endo reverting to the response of luteal NP-UA Endo. This demonstrates the importance of adaptation of cell signaling over eNOS expression in pregnancy adaptation of uterine endothelial function and further implicates VEGF in the pathophysiology of preeclampsia.
Heme oxygenase metabolites inhibit tubuloglomerular feedback in vivo
Authors: Wang Hong , Garvin Jeffrey L. , D'Ambrosio Martin A. , Falck John R. , Leung Pablo , Liu Ruisheng , Ren YiLin , Carretero Oscar A.
Published: January 2011

Tubuloglomerular feedback (TGF) is a renal autoregulatory mechanism that constricts the afferent arteriole in response to increases in distal NaCl. Heme oxygenases (HO-1 and HO-2) release carbon monoxide (CO) and biliverdin, which may help control renal function. We showed in vitro that HO products inhibit TGF; however, we do not know whether this also occurs in vivo or the mechanism(s) involved. We hypothesized that in vivo HO-1 and HO-2 in the nephron inhibit TGF via release of CO and biliverdin. We first performed laser capture microdissection followed by real-time PCR and found that both HO-1 and HO-2 are expressed in the macula densa. We next performed micropuncture experiments in vivo on individual rat nephrons, adding different compounds to the perfusate, and found that an HO inhibitor, stannous mesoporphyrin (SnMP), potentiated TGF ( P < 0.05, SnMP vs. control). The CO-releasing molecule (CORM)-3 partially inhibited TGF at 50 μmol/l ( P < 0.01, CORM-3 vs. control) and blocked it completely at higher doses. A soluble guanylyl cyclase (sGC) inhibitor, LY83583, blocked the inhibitory effect of CORM-3 on TGF. Biliverdin also partially inhibited TGF ( P < 0.01, biliverdin vs. control), most likely attributable to decreased superoxide (O2−) because biliverdin was rendered ineffective by tempol, a O2− dismutase mimetic. We concluded that HO-1 and HO-2 in the nephron inhibit TGF by releasing CO and biliverdin. The inhibitory effect of CO on TGF is mediated by the sGC/cGMP signaling pathway, whereas biliverdin probably acts by reducing O2−.
Nitric oxide suppression of cellular proliferation depends on cationic amino acid transporter activity in cytokine-stimulated pulmonary endothelial cells
Authors: Chicione Louis G. , Stenger Michael R. , Cui Hongmei , Calvert Andrea , Evans Rebecca J. , English B. Keith , Liu Yusen , Nelin Leif D.
Published: January 2011

Inducible nitric oxide (NO) synthase (iNOS) is a stress response protein upregulated in inflammatory conditions, and NO may suppress cellular proliferation. We hypothesized that preventing l-arginine (l-arg) uptake in endothelial cells would prevent lipopolysaccharide/tumor necrosis factor-α (LPS/TNF)-induced, NO-mediated suppression of cellular proliferation. Bovine pulmonary arterial endothelial cells (bPAEC) were treated with LPS/TNF or vehicle (control), and either 10 mM l-leucine [l-leu; a competitive inhibitor of l-arg uptake by the cationic amino acid transporter (CAT)] or its vehicle. In parallel experiments, iNOS or arginase II were overexpressed in bPAEC using an adenoviral vector (AdiNOS or AdArgII, respectively). LPS/TNF treatment increased the expression of iNOS, arginase II, CAT-1, and CAT-2 mRNA in bPAEC, resulting in greater NO and urea production than in control bPAEC, which was prevented by l-leu. LPS/TNF treatment resulted in fewer viable cells than in controls, and LPS/TNF-stimulated bPAEC treated with l-leu had more viable cells than LPS/TNF treatment alone. LPS/TNF treatment resulted in cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase expression, which was attenuated by l-leu. AdiNOS reduced viable cell number, and treatment of AdiNOS transfected bPAEC with l-leu preserved cell number. AdArgII increased viable cell number, and treatment of AdArgII transfected bPAEC with l-leu prevented the increase in cell number. These data demonstrate that iNOS expression in pulmonary endothelial cells leads to decreased cellular proliferation, which can be attenuated by preventing cellular l-arg uptake. We speculate that CAT activity may represent a novel therapeutic target in inflammatory lung diseases characterized by NO overproduction.
Hypoxia-inducible factor-1α mediates TGF-β-induced PAI-1 production in alveolar macrophages in pulmonary fibrosis
Authors: Ueno Manabu , Maeno Toshitaka , Nomura Miyuki , Aoyagi-Ikeda Kana , Matsui Hiroki , Hara Kenichiro , Tanaka Toru , Iso Tatsuya , Suga Tatsuo , Kurabayashi Masahiko
Published: January 2011

Hypoxia-inducible factor-1α (HIF-1α), a transcription factor that functions as a master regulator of oxygen homeostasis, has been implicated in fibrinogenesis. Here, we explore the role of HIF-1α in transforming growth factor-β (TGF-β) signaling by examining the effects of TGF-β1on the expression of plasminogen activator inhibitor-1 (PAI-1). Immunohistochemistry of lung tissue from a mouse bleomycin (BLM)-induced pulmonary fibrosis model revealed that expression of HIF-1α and PAI-1 was predominantly induced in alveolar macrophages. Real-time RT-PCR and ELISA analysis showed that PAI-1 mRNA and activated PAI-1 protein level were strongly induced 7 days after BLM instillation. Stimulation of cultured mouse alveolar macrophages (MH-S cells) with TGF-β1induced PAI-1 production, which was associated with HIF-1α protein accumulation. This accumulation of HIF-1α protein was inhibited by SB431542 (type I TGF-β receptor/ALK receptor inhibitor) but not by PD98059 (MEK1 inhibitor) and SB203580 (p38 MAP kinase inhibitor). Expression of prolyl-hydroxylase domain (PHD)-2, which is essential for HIF-1α degradation, was inhibited by TGF-β1, and this decrease was abolished by SB431542. TGF-β1induction of PAI-1 mRNA and its protein expression were significantly attenuated by HIF-1α silencing. Transcriptome analysis by cDNA microarray of MH-S cells after HIF-1α silencing uncovered several pro-fibrotic genes whose regulation by TGF-β1required HIF-1α, including platelet-derived growth factor-A. Taken together, these findings expand our concept of the role of HIF-1α in pulmonary fibrosis in mediating the effects of TGF-β1on the expression of the pro-fibrotic genes in activated alveolar macrophages.
CTGF disrupts alveolarization and induces pulmonary hypertension in neonatal mice: implication in the pathogenesis of severe bronchopulmonary dysplasia
Authors: Chen Shaoyi , Rong Min , Platteau Astrid , Hehre Dorothy , Smith Heather , Ruiz Philip , Whitsett Jeffrey , Bancalari Eduardo , Wu Shu
Published: January 2011

The pathological hallmarks of bronchopulmonary dysplasia (BPD), one of the most common long-term pulmonary complications associated with preterm birth, include arrested alveolarization, abnormal vascular growth, and variable interstitial fibrosis. Severe BPD is often complicated by pulmonary hypertension characterized by excessive pulmonary vascular remodeling and right ventricular hypertrophy that significantly contributes to the mortality and morbidity of these infants. Connective tissue growth factor (CTGF) is a multifunctional protein that coordinates complex biological processes during tissue development and remodeling. We have previously shown that conditional overexpression of CTGF in airway epithelium under the control of the Clara cell secretory protein promoter results in BPD-like architecture in neonatal mice. In this study, we have generated a doxycycline-inducible double transgenic mouse model with overexpression of CTGF in alveolar type II epithelial (AT II) cells under the control of the surfactant protein C promoter. Overexpression of CTGF in neonatal mice caused dramatic macrophage and neutrophil infiltration in alveolar air spaces and perivascular regions. Overexpression of CTGF also significantly decreased alveolarization and vascular development. Furthermore, overexpression of CTGF induced pulmonary vascular remodeling and pulmonary hypertension. Most importantly, we have also demonstrated that these pathological changes are associated with activation of integrin-linked kinase (ILK)/glucose synthesis kinase-3β (GSK-3β)/β-catenin signaling. These data indicate that overexpression of CTGF in AT II cells results in lung pathology similar to those observed in infants with severe BPD and that ILK/GSK-3β/β-catenin signaling may play an important role in the pathogenesis of severe BPD.
Lung-derived soluble mediators are pathogenic in ventilator-induced lung injury
Authors: Jaecklin Thomas , Engelberts Doreen , Otulakowski Gail , O'Brodovich Hugh , Post Martin , Kavanagh Brian P.
Published: January 2011

Ventilator-induced lung injury (VILI) due to high tidal volume (VT) is associated with increased levels of circulating factors that may contribute to, or be markers of, injury. This study investigated if exclusively lung-derived circulating factors produced during high VTventilation can cause or worsen VILI. In isolated perfused mouse lungs, recirculation of perfusate worsened injury (compliance impairment, microvascular permeability, edema) induced by high VT. Perfusate collected from lungs ventilated with high VTand used to perfuse lungs ventilated with low VTcaused similar compliance impairment and permeability and caused a dose-dependent decrease in transepithelial electrical resistance (TER) across rat distal lung epithelial monolayers. Circulating soluble factors derived from the isolated lung thus contributed to VILI and had deleterious effects on the lung epithelial barrier. These data demonstrate transferability of an injury initially caused exclusively by mechanical ventilation and provides novel evidence for the biotrauma hypothesis in VILI. Mediators of the TER decrease were heat-sensitive, transferable via Folch extraction, and (following ultrafiltration, 3 kDa) comprised both smaller and larger molecules. Although several classes of candidate mediators, including protein cytokines (e.g., tumor necrosis factor-α, interleukin-6, macrophage inflammation protein-1α) and lipids (e.g., eicosanoids, ceramides, sphingolipids), have been implicated in VILI, only prostanoids accumulated in the perfusate in a pattern consistent with a pathogenic role, yet cyclooxygenase inhibition did not protect against injury. Although no single class of factor appears solely responsible for the decrease in barrier function, the current data implicate lipid-soluble protein-bound molecules as not just markers but pathogenic mediators in VILI.
In vivo function of airway epithelial TLR2 in host defense against bacterial infection
Authors: Wu Qun , Jiang Di , Minor Maisha N. , Martin Richard J. , Chu Hong Wei
Published: January 2011

Decreased Toll-like receptor 2 (TLR2) expression has been reported in patients with chronic obstructive pulmonary disease and in a murine asthma model, which may predispose the hosts to bacterial infections, leading to disease exacerbations. Since airway epithelial cells serve as the first line of respiratory mucosal defense, the present study aimed to reveal the role of airway epithelial TLR2 signaling to lung bacterial [i.e., Mycoplasma pneumoniae (Mp)] clearance. In vivo TLR2 gene transfer via intranasal inoculation of adenoviral vector was performed to reconstitute TLR2 expression in airway epithelium of TLR2−/−BALB/c mice, with or without ensuing Mp infection. TLR2 and lactotransferrin (LTF) expression in airway epithelial cells and lung Mp load were assessed. Adenovirus-mediated TLR2 gene transfer to airway epithelial cells of TLR2−/−mice reconstituted 30–40% TLR2 expression compared with TLR2+/+cells. Such airway epithelial TLR2 reconstitution in TLR2−/−mice significantly reduced lung Mp load (an appropriate 45% reduction), coupled with elevated LTF expression. LTF expression in mice was shown to be mainly dependent on TLR2 signaling in response to Mp infection. Exogenous human LTF protein dose-dependently decreased lung bacterial load in Mp-infected TLR2−/−mice. In addition, human LTF protein directly dose-dependently decreased Mp levels in vitro. These data indicate that reconstitution of airway epithelial TLR2 signaling in TLR2−/−mice significantly restores lung defense against bacteria (e.g., Mp) via increased lung antimicrobial protein LTF production. Our findings may offer a deliverable approach to attenuate bacterial infections in airways of asthma or chronic obstructive pulmonary disease patients with impaired TLR2 function.
Cell deformation at the air-liquid interface induces Ca2+-dependent ATP release from lung epithelial cells
Authors: Ramsingh Ronaldo , Grygorczyk Alexandra , Solecki Anna , Cherkaoui Lalla Siham , Berthiaume Yves , Grygorczyk Ryszard
Published: January 2011

Extracellular nucleotides regulate mucociliary clearance in the airways and surfactant secretion in alveoli. Their release is exquisitely mechanosensitive and may be induced by stretch as well as airflow shear stress acting on lung epithelia. We hypothesized that, in addition, tension forces at the air-liquid interface (ALI) may contribute to mechanosensitive ATP release in the lungs. Local depletion of airway surface liquid, mucins, and surfactants, which normally protect epithelial surfaces, facilitate such release and trigger compensatory mucin and fluid secretion processes. In this study, human bronchial epithelial 16HBE14o−and alveolar A549 cells were subjected to tension forces at the ALI by passing an air bubble over the cell monolayer in a flow-through chamber, or by air exposure while tilting the cell culture dish. Such stimulation induced significant ATP release not involving cell lysis, as verified by ethidium bromide staining. Confocal fluorescence microscopy disclosed reversible cell deformation in the monolayer part in contact with the ALI. Fura 2 fluorescence imaging revealed transient intracellular Ca2+elevation evoked by the ALI, which did not entail nonspecific Ca2+influx from the extracellular space. ATP release was reduced by ∼40 to ∼90% from cells loaded with the Ca2+chelator BAPTA-AM and was completely abolished by N-ethylmalemide (1 mM). These experiments demonstrate that in close proximity to the ALI, surface tension forces are transmitted directly on cells, causing their mechanical deformation and Ca2+-dependent exocytotic ATP release. Such a signaling mechanism may contribute to the detection of local deficiency of airway surface liquid and surfactants on the lung surface.
LPS-induced decrease in intracellular labile zinc, [Zn]i, contributes to apoptosis in cultured sheep pulmonary artery endothelial cells
Authors: Thambiayya Kalidasan , Wasserloos Karla J. , Huang Zhentai , Kagan Valerian E. , St. Croix Claudette M. , Pitt Bruce R.
Published: January 2011

A role in signal transduction for a vanishingly small labile pool of intracellular zinc ([Zn]i) has been inferred by the sensitivity of various physiological pathways to zinc chelators such as N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and/or associations with changes in nonprotein-bound zinc-sensitive fluorophores. Although we ( 44 ) reported that LPS-induced apoptosis in cultured sheep pulmonary artery endothelial cells (SPAEC) was exacerbated by TPEN, 1) we did not detect acute (30 min) changes in [Zn]i, and 2) it is unclear from other reports whether LPS increases or decreases [Zn]iand whether elevations or decreases in [Zn]iare associated with cell death and/or apoptosis. In the present study, we used both chemical (FluoZin-3 via live cell epifluorescence microscopy and fluorescence-activated cell sorting) and genetic (luciferase activity of a chimeric reporter encoding zinc-sensitive metal-response element and changes in steady-state mRNA of zinc importer, SLC39A14 or ZIP14) techniques to show that LPS caused a delayed time-dependent (2–4 h) decrease in [Zn]iin SPAEC. A contributory role of decreases in [Zn]iin LPS-induced apoptosis (as determined by caspase-3/7 activation, annexin-V binding, and cytochrome c release) in SPAECs was revealed by mimicking the effect of LPS with the zinc chelator, TPEN, and inhibiting LPS- (or TPEN)-induced apoptosis with exogenous zinc. Collectively, these are the first data demonstrating a signaling role for decrease in [Zn]iin pulmonary endothelial cells and suggest that endogenous levels of labile zinc may affect sensitivity of pulmonary endothelium to the important and complex proapoptotic stimulus of LPS.
The HIF-1–Inducible Lysyl Oxidase Activates HIF-1 via the Akt Pathway in a Positive Regulation Loop and Synergizes with HIF-1 in Promoting Tumor Cell Growth
Authors: Pez Floriane , Dayan Frédéric , Durivault Jérome , Kaniewski Bastien , Aimond Géraldine , Le Provost Gabrielle S. , Deux Blandine , Clézardin Philippe , Sommer Pascal , Pouysségur Jacques , Reynaud Caroline
Published: January 2011

Adaptation to hypoxia is a driving force for tumor progression that leads to therapy resistance and poor clinical outcome. Hypoxic responses are mainly mediated by hypoxia-inducible transcription factor-1 (HIF-1). One critical HIF-1 target mediating tumor progression is lysyl oxidase (LOX), which catalyzes cross-linking of collagens and elastin in the extracellular matrix, thereby regulating tissue tensile strength. Paradoxically, LOX has been reported to be both upregulated and downregulated in cancer cells, especially in colorectal cancer. Thus, we hypothesized that LOX might regulate expression of HIF-1 to create a self-timing regulatory circuit. Using human colorectal carcinoma cell lines in which HIF-1 and LOX expression could be modulated, we showed that LOX induction enhanced HIF-1 expression, whereas LOX silencing reduced it. Mechanistic investigations revealed that LOX activated the PI3K (phosphoinositide 3-kinase)–Akt signaling pathway, thereby upregulating HIF-1α protein synthesis in a manner requiring LOX-mediated hydrogen peroxide production. Consistent with these results, cancer cell proliferation was stimulated by secreted and active LOX in an HIF-1α–dependent fashion. Furthermore, nude mice xenograft assays established that HIF-1 potentiated LOX action on tumor growth in vivo. Taken together, these findings provide compelling evidence that LOX and HIF-1 act in synergy to foster tumor formation, and they suggest that HIF-1/LOX mutual regulation is a pivotal mechanism in the adaptation of tumor cells to hypoxia. Cancer Res; 71(5); 1647–57. ©2011 AACR.
Eddy and Wind-Forced Heat Transports in the Gulf of Mexico
Authors: Chang Y-L. , Oey L-Y.
Published: January 2011

The Gulf of Mexico (GOM) receives heat from the Caribbean Sea via the Yucatan–Loop Current (LC) system, and the corresponding ocean heat content (OHC) is important to weather and climate of the continental United States. However, the mechanisms that affect this heat influx and how it is distributed in the Gulf have not been studied. Using the Princeton Ocean Model, the authors show that a steady, uniform westward wind in the Gulf increases (∼100 KJ cm−2) the upper OHC (temperature T > 18°C) of the Gulf. This is because wind increases the water exchange between the Gulf and the Caribbean Sea, and the heat input into the Gulf is also increased, by about 50 TW. The westward heat transport to the western Gulf is ∼30 TW, and a substantial portion of this is due to wind-induced shelf currents, which converge to produce downwelling near the western coast. Finally, eddies are effective transporters of heat across the central Gulf. Wind forces larger LC and rings with deeper isotherms. This and downfront-wind mixing on the southern side of anticyclonic rings, northward spread of near-zero potential vorticity waters, and downwelling on the northern shelf break result in wide and deep eddies that transport large OHCs across the Gulf.
Adding Nuance to the Study of Political Humor Effects: Experimental Research on Juvenalian Satire Versus Horatian Satire
Authors: Holbert R. Lance , Hmielowski Jay , Jain Parul , Lather Julie , Morey Alyssa
Published: January 2011

This study extends political humor effects research by focusing on two distinct types of satire, juvenalian and horatian. Theoretical arguments grounded in the elaboration likelihood model culminated in the positing of a series of interactions between message (juvenalian, horatian, traditional opinion-editorial) and recipient ability (high, low) relative to three outcome variables: perceived humor, counterarguing, and attitudes concerning Hillary Clinton’s universal health care plan. An experiment was conducted during the 2008 Democratic primary election. The Message × Ability interactions revealed a need to step beyond the study of satire as monolithic; different types of satire produce divergent effects depending on the ability of the audience member. Future lines of research and the need for additional theory building are discussed.
L’application de la spiritualité bénédictine au loisir des personnes âgées : un modèle théorique du bonheur spirituel
Authors: Ouellette Pierre , Snyder Patrick , Carette Raymond
Published: January 2011

Le but de cette réflexion théologique est de montrer, à l’aide d’un modèle théorique, comment l’application de la spiritualité bénédictine au loisir des personnes âgées peut favoriser le bonheur spirituel. L’analyse s’est articulée notamment autour d’un syllogisme. Le cœur de la spiritualité bénédictine est la contemplation. Or, les personnes âgées sont tout naturellement disposées à la réminiscence, à l’introspection et à la contemplation. Donc, la spiritualité bénédictine convient particulièrement au loisir des personnes âgées. Quatre valeurs bénédictines ont été retenues, à savoir la fraternité, la modération, l’hospitalité et l’humilité. Dans le modèle, la spiritualité bénédictine est reliée à la contemplation, à l’union avec Dieu et au bonheur spirituel. Par ailleurs, la spiritualité bénédictine, le loisir contemplatif et les personnes âgées sont interreliés; en plus, les personnes âgées et le loisir contemplatif sont directement reliés à la contemplation. Bref, il s’agissait de jeter un regard bénédictin sur le loisir, le vieillissement et le bonheur.

The purpose of this theological reflection is the application of Benedictine spirituality to the leisure of older people. Based on a syllogism, it presupposes that the heart of Benedictine spirituality is contemplation. Hence, older people are predisposed to reminiscence, introspection and contemplation. Therefore, Benedictine spirituality is particularly appropriate for the leisure of older people. Four Benedictine values were selected namely fraternity, moderation, hospitality and humility. Also in a proposed theoretical model, Benedictine spirituality is related to contemplation, union with God and spiritual happiness. Furthermore, Benedictine spirituality, contemplative leisure and older people are all interrelated while older people and contemplation are directly related to contemplation. Essentially, this paper aimed at providing a monastic outlook on happiness, aging and contemplative leisure.
A Socially Resilient Urban Transition? The Contested Landscapes of Apartment Building Extensions in Two Post-communist Cities
Authors: Bouzarovski Stefan , Salukvadze Joseph , Gentile Michael
Published: January 2011

Even though social processes across the globe are increasingly being theorised through a resilience lens, this has rarely been the case within the domain of everyday life in the city. The resilience debate also remains highly geographically selective, as regions that have undergone far-reaching systemic change over the past 20 years—including the post-communist states of the former Soviet Union and eastern and central Europe (ECE)—generally remain omitted from it. In order to address such knowledge gaps, an investigation is made of the relationships between social resilience and micro-level socio-spatial change in the built environment of the post-communist city, by focusing on the institutional, spatial and economic underpinnings of apartment building extensions (ABEs) on multistorey residential buildings in the Macedonian capital of Skopje and the Georgian capital of Tbilisi. Both cities contain a wide variety of ABEs, whose reinforced concrete frame constructions often rival the host buildings in terms of size and function. By exploring the architectural and social landscapes created by the extensions, it is hoped to highlight their embeddedness in a set of policy decisions and coping strategies, as well as their controversial implications on the present and future use of urban space.
Expectations about and impact of the Liverpool Care Pathway for the dying patient in an Italian hospital
Authors: Di Leo Silvia , Beccaro Monica , Finelli Stefania , Borreani Claudia , Costantini Massimo
Published: January 2011

This study is aimed at exploring the expectations about and the impact on healthcare staff of the Liverpool Care Pathway for the dying patient (LCP) in an Italian hospital. Qualitative information was derived from four focus group (FG) meetings that were carried out separately by profession and scheduled before the beginning and after the end of the implementation process of the Italian version of LCP for hospitals (LCP-I). Interview topics concerned end-of-life care related problems and expectations about the impact of the LCP-I programme. Tape recordings of the FGs were transcribed verbatim, and transcripts analysed independently by two research psychologists using thematic analysis.

Five major topics were identified: managing pain and discontinuing inappropriate treatments, communicating with patients, communicating with relatives, communicating between professionals and practical issues. As compared with those reported in the initial FGs, responses from the final FGs highlighted that physicians felt more confident with pain management and with discontinuing inappropriate treatment, and were more inclined to recognize the value of the nurses’ work. Nurses underlined advantages in using pro re nata medication, but stressed lack of personnel and time as obstacles in consistent improvement of end-of-life care. All participants seemed to acquire greater awareness of their difficulties in communication and, paradoxically, became more uncertain of their ability to liaise with dying patients and their families.

LCP-I implementation may improve both knowledge about physical symptom management and professional awareness of the problems related to emotional and informative support in end-of-life care.
Mortality of One-Week-Old Chickens During Naturally Occurring Marek’s Disease Virus Infection
Authors: Carvallo F. R. , French R. A. , Gilbert-Marcheterre K. , Risatti G. , Dunn J. R. , Forster F. , Kiupel M. , Smyth J. A.
Published: January 2011

Marek’s disease (MD) is a disease of chickens that occurs worldwide and has serious economic consequences. MD can present as one of several forms, with the most commonly occurring forms being the lymphoproliferative diseases. Under experimental conditions, an early mortality syndrome has been recognized following infection by some but not all strains of MD virus (MDV). This is the first report of a confirmed case of mortality due to naturally occurring MDV infection in 1-week-old, nonvaccinated, chickens. Necrotizing lesions were observed in the bursa of Fabricius, lung, duodenum, jejunum, and proventriculus, and large intranuclear inclusion bodies were a striking feature in tissues with lesions in all birds. Immunohistochemical staining for the pp38 protein of MDV revealed abundant pp38 antigen in the affected tissues, confirming the presence of MDV within the lesions. PCR yielded an amplicon with 97% homology to the meq gene of MDV. No evidence of co-infection by either of the immunosuppressive agents chicken anemia virus and infectious bursal disease virus was detected.
Towards a holistic model of functions of music listening across cultures: A culturally decentred qualitative approach
Authors: Boer Diana , Fischer Ronald
Published: January 2011

The present article explores the functions of music listening from a cross-cultural perspective. We present a model of functions of music listening based on a multicultural qualitative approach. Our model covers personal, social and cultural musical experiences. Seven main functions of music listening were identified: music in the background, memories through music, music as diversion, emotions and self-regulation through music, music as reflection of self and social bonding through music. Our model was confirmed in an independent sample using a cross-method validation. Quantitative analyses of the qualitative data explored the salience of functions of music listening across four sub-samples: Asian and Latin-American sub-samples being more collectivistic and non- Anglophone Western and Anglophone Western sub-samples being more individualistic. Across all sub-samples the self-regulation function was the most important personal use of music, bonding was the most important social use of music and the expression of cultural identity was the most salient cultural function of music regardless of listeners’ cultural background. Apart from these similarities which point towards universalities, we also revealed cross-cultural differences pointing towards culture-specific uses of music. Limitations in the methodology of this exploratory cross-cultural approach and future directions in cross-cultural psychology of music are discussed.
Free radical scavenging and antiacetylcholinesterase activities ofOriganum majoranaL. essential oil
Authors: Mossa A T H , Nawwar GAM
Published: January 2011

In the present study, Origanum majorana L. essential oil (EO) was analyzed by gas chromatography-mass spectrometry (GC-MS) and evaluated for free radical scavenging and anticholinesterase activities. GC-MS analysis revealed the presence of 4-terpineol (29.97%), γ-terpinene (15.40%), trans-sabinene hydrate (10.93), α-terpinene (6.86%), 3-cycolohexene-1-1 methanal,a,a4-trimethyl-,(S)-(CAS) (6.54%), and sabinene (3.91%) as main constituents. Origanum majorana L. EO exhibited concentration-dependent inhibitory effects on 2,2′-diphenylpicrylhydrazyl (DPPH•), hydroxyl radical, hydrogen peroxide, reducing power, and lipid peroxidation with IC50values of 58.67, 67.11, 91.25, 78.67, and 68.75 µg/mL, respectively; while the IC50values for the standard trolox were noted to be 23.95, 44.97, 51.30, 42.22, and 52.72 µg/mL, respectively. Interestingly, cholinesterase inhibitory activity was also found with IC50values of 36.40 µg/mL. We can conclude that the marjoram EO has a significant potential to be used as a natural antioxidant and anti-AChE.
Fenvalerate induced hepatic oxidative stress in selenium- and/or iodine-deficient rats
Authors: Giray Belma , Hincal Filiz
Published: January 2011

Considering the potential adverse effects of selenium and iodine deficiencies, and frequency of intensive but improper use of insecticides, this study was designed to evaluate the effects of a pyrethroid insecticide, fenvalerate, on the oxidant/antioxidant status of liver using a rat model of iodine and/or selenium deficiency. The study was conducted on eight groups of 3-week old Wistar rats. Iodine and/or selenium deficiency was introduced by feeding the animals with a diet containing <0.005 mg selenium/kg and/or supplying with 1% sodium perchlorate containing drinking water for a period of 7 weeks. Fenvalerate exposure (100 mg/kg/d, i.p., for the last 7 days) in normal rats increased hepatic glutathione peroxidase activity and lipid peroxidation, decreased glutathione content, but did not change the activities of catalase or any of the superoxide dismutase forms; in iodine-deficient animals caused only the elevation of lipid peroxidation; in selenium-deficient animals and in combined iodine/selenium deficiency decreased glutathione peroxidase, increased catalase activities and lipid peroxidation, and decreased all the forms of superoxide dismutase activity only in combined deficiency. These results suggested that fenvalerate is an oxidant stress inducer in rat liver, and its potential effects on pro-oxidant/antioxidant balance may also be important for human populations, particularly with iodine and/or selenium deficiencies.
Anti-hepatotoxic effects of 3,4-methylenedioxyphenol andN-acetylcysteine in acutely acetaminophen-overdosed mice
Authors: Chandrasekaran Victor Raj Mohan , Chien Se-Ping , Hsu Dur-Zong , Liu Ming-Yie
Published: January 2011

3,4-Methylenedioxyphenol (sesamol) is effective against acetaminophen-induced liver injury in rats. Whether sesamol’s anti-hepatotoxic effect is comparable to that of N-acetylcysteine has never been studied. We investigated the anti-hepatotoxic effects of sesamol and N-acetylcysteine on acetaminophen-induced hepatotoxicity in mice. Equimolar doses (1 mmol/kg) of sesamol and N-acetylcysteine significantly inhibited acetaminophen (300 mg/kg)-increased serum aspartate transaminase and alanine transaminase levels 6 h post-administration. Sesamol and N-acetylcysteine maintained hepatic glutathione levels and inhibited lipid peroxidation. Moreover, the combination of sesamol and N-acetylcysteine antagonistically inhibited sesamol’s protection against acetaminophen-induced liver injury. We conclude that the protective effect of sesamol against acetaminophen-induced liver damage is comparable to that of N-acetylcysteine by maintaining glutathione levels and inhibiting lipid peroxidation in mice.
Classic Major Histocompatibility Complex Class I Molecules: New Actors at the Neuromuscular Junction
Authors: Cullheim Staffan , Thams Sebastian
Published: January 2011

The presence and function of immune molecules in the central nervous system (CNS) have been under debate for a long time. There is mounting evidence that molecules fundamental for immune function are indeed expressed by both neurons and glia and that such molecules may have important nonimmunological function for the organization and stability of synaptic connections. Here, we present data showing that the classic form of major histocompatibility complex (MHC) class I molecules is expressed in spinal motoneurons, in particular in their axons and presynaptically at their synapses with skeletal muscles, the neuromuscular junctions (NMJs). The expression is strongly increased after axon lesion in the peripheral nerve. In the absence of classic MHC I, the organization of NMJs is disturbed with NMJs in higher numbers than normal, thereby equipping single muscle fibers with multiple NMJs. It is suggested that these effects are mediated by the classic MHC class I in the motor axons, possibly through effects mediated by the peripherally myelinating Schwann cells, which express receptors for classic MHC class I. The presence of immune molecules normally used by other cells for antigen presentation in peripheral motor axons may have implications for the onset of specific motoneuron disease.