bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection and test of effective chelators for removal of heavy metals from contaminated soils
Authors: Chen Ting-Chien , Macauley Edward , Hong Andrew
Published: January 2010

Heavy metal contamination of soil is a common problem at many hazardous waste sites. Chelating extraction of heavy metals has been proposed as a remediation technique for contaminated soils. A useful method was developed, which assessed 190 ligands for their ability in extraction and recovery of target metals, including cadmium, copper, lead, mercury, nickel, and zinc. Chelator performance was evaluated based on equilibrium calculations with an emphasis on the potential of recovering both the metals and chelating agents. Batch equilibration experiments over 24-h periods were performed to test three chelating agents, S-carboxymethyl-cysteine (SCMC), N-2-acetamidoiminodiacetic acid (ADA), and pyridine-2,6-dicarboxylic acid (PDA), which were deemed suitable for the extraction of cadmium, copper, lead, and zinc from soil. All three chelators demonstrated high extraction capability toward their respective target metals across a wide range of pH, metal, and ligand concentrations. In addition, all three chelators exhibited good recovery potential at moderately elevated pH values. The potential of many chelating agents and their effective pH ranges in the remediation of soils contaminated with heavy metals are reported. Key words: heavy metal, soil, contamination, chelation, remediation.
Influence d'un préconditionnement chimique sur l'épaississement gravitaire et la déshydratation de boues d'étangs aérés facultatifs
Authors: Desjardins Marc-André , Bussières Charles , Brière François G. , Dagenais Danielle
Published: January 2010

This article presents the results of a study on the influence of chemical preconditioning on gravity thickening and dewatering of biological and chemical sludge (alum dephosphatation sludge) from facultative aerated lagoons. Four reagents have been studied: two cationic polymers and two inorganic reagents. Inorganic reagents have not improved gravity thickening of sludge while polymers were more efficient. Polymers have a dual effect: they increase capture rate and accelerate solids settling. Biological sludge from lagoons thickens easily and may reach 10 to 12% dry solid contents, with or without the addition of polymers. On the contrary, chemical sludge thickens with great difficulty. Even with the addition of polymers, the maximum dry solid content did not reach more than 3.8% for sludge with initial dry solid content of 1.25% approximately. However, higher dry solid content can be obtained if the initial dry solid content of sludge is higher. Therefore, it is important to minimize dilution during the extraction of sludge from lagoons. Finally, the addition of polymers to sludge to help thickening does not affect the reconditioning of sludge to be dewatered except possibly in the case of mechanically dewatered chemical sludge treated with chemical conditioning. Key words: chemical preconditioning, gravity thickening, dewatering, sludge, facultative aerated lagoons.
Increasing job opportunities in a subregion for region-wide fuel conservation and air-quality improvement
Authors: Tayyaran M. R. , Khan A. M.
Published: January 2010

Presently, there is much interest in defining urban development patterns for reducing energy consumption in transportation and in improving air quality. This research examined the effects of improving job opportunities in a subregion on region-wide transportation fuel consumption and emissions. A research framework, consisting of travel simulation models, and energy and emissions factors, was developed for testing land use – transportation scenarios. The travel simulation modelling framework consisted of the four-step approach, including the calibration of trip distribution and modal split models. Fuel consumption and emissions were estimated by using vehicle kilometres of travel. The city of Kanata within the Regional Municipality of Ottawa – Carleton, Canada, was used as a case study. Five scenarios illustrating possible future employment schemes were developed. Vehicle kilometres, fuel, and emissions for both automobile and public transit were estimated for year 2011 scenarios. The results are presented as totals for both the overall National Capital Area and for the subregion, Kanata. From these results, it is concluded that providing more job opportunities and enhancing the job to housing ratio in a satellite city could reduce fuel consumption and emissions from a regional perspective. Key words: air pollution, emissions, fuel consumption, land use, transportation modelling, simulation.
Optimization of the Regional Municipality of Ottawa-Carleton's water supply system operations. II. Model results and analyses
Authors: Pelletier Geneviève , Townsend Ronald D.
Published: January 2010

The principal objective of this study was to optimize pump scheduling and reservoir releases in the Regional Municipality of Ottawa-Carleton's (RMOC) water supply system with a view to reducing hydro-related operating costs. Basically, hourly demands are to be met with minimum pumping costs. The preceding paper (part I) describes the RMOC system and the numerical model used in the optimization analysis. This paper (part II) presents the main results obtained from the optimization and also reports on the second study objective, which was to investigate the impacts on system operating costs of increasing (i) reservoir storage capacity, (ii) treatment plant capacity, and (iii) water demand by consumers. In general, linear programming was found to be a good modelling option for generating optimized pump schedules and service reservoir releases. The analyses of water management alternatives confirmed that RMOC's water supply system was designed for maximum day water demand; however, day-to-day operations would be facilitated if present storage and (or) treatment facilities were enlarged. Economically, it would be difficult to justify construction costs from the potential energy savings obtained from this study and therefore it seems important to start managing demand. Key words: water supply system, pump scheduling, pumping costs, optimization, modelling.
Design of single-angle compression members according to the Canadian standards
Authors: Temple Murray C.
Published: January 2010

Although single-angle compression members, attached by one leg, appear to be very simple structural elements, they are amongst the most complex of structural elements to analyze and design. This is due to the end eccentricities and the fact that the principal axes of the angle do not coincide with the axis of the structure. The design of single-angle compression members, according to the Canadian standards, is not as straightforward as might be expected. There are numerous clauses to be considered in two standards. In some cases, all failure modes are not covered explicitly. The Canadian standards are examined and applied to the two generally accepted design approaches used in Canada and the United States. These approaches are (i) to ignore the end eccentricities and to treat the angle as a concentrically loaded member and (ii) to account for the end eccentricities by treating the angle as a beam–column. A flow chart is presented which will guide the designer through the many clauses that have to be considered in the two standards. Some suggestions are made which should help a practicing engineer design single-angle compression members that are attached by one leg. Key words: angles, buckling, building (codes), design.
Thermal stressing of plain and prestressed masonry diaphragm walls
Authors: Shrive N. G. , Huizer A. , Tilleman D. , Eng W.
Published: January 2010

Diaphragm walls constitute a structurally efficient form of masonry. The effects of the large cross-wall temperature differentials which can develop during winter need to be examined. Finite element models of diaphragm walls were analysed to determine if thermal stresses could potentially cause structural distress. For validation, model walls were subjected to flexural loading and the results were compared with those from experimental tests on similar walls. Good agreement was found. Therefore, thermal analyses were performed. It was found that the resulting stresses were heavily dependent on the structural boundary conditions, but indicated the potential of cracking. Series of 2 and 3 m high walls were therefore constructed and subjected to thermal loading. The walls were subjected to different boundary conditions. The 3 m high walls were tested both plain and prestressed. None of the walls cracked as a result of the thermal loading. A simple method is presented for estimating the change in prestress force due to the temperature change in the wall. Key words: masonry, diaphragm walls, cavity walls, thermal tests, post-tensioning finite element modelling.
Strengthening of existing concrete dams using post-tensioned anchors: a state-of-the-art review
Authors: Xu Haixue , Benmokrane Brahim
Published: January 2010

Many old dams are in need of strengthening and rehabilitation as a result of aging, deterioration, deficiencies in design and construction, and more stringent safety standards. These standards include the probable maximum flood and the maximum credible earthquake. Post-tensioned anchors are the most practical and cost-effective method of strengthening existing concrete dams subjected to direct tension, sliding, overturning and seismic loading. In some cases, they are used to stabilize rock abutments and concrete locks and to combat the effects of alkaline and aggregate reaction. The post-tensioning technique requires minimum demolition, has only a minor impact on the dam, and is relatively inexpensive using a small number of anchors. This paper reviews about 60 case histories of concrete dams strengthened by post-tensioned anchors. The reasons for strengthening existing dams are analyzed. The general design, construction, drilling, grouting, testing, and performance of post-tensioned anchors for strengthening concrete dams are outlined. Key words: post-tensioned, anchor, multistrand, fixed anchor length, free anchor length, anchor head, strengthening, rehabilitation, concrete dam.
CYLINDRICAL CONTACT HOMOLOGY OF A DEHN TWIST
Authors: YAU MEI-LIN
Published: December 2009

We use open book representations of contact 3-manifolds to compute the cylindrical contact homology of a Stein-fillable contact 3-manifold represented by the open book whose monodromy is a positive Dehn twist on a torus with boundary.
SEVERI VARIETIES AND SELF-RATIONAL MAPS OF K3 SURFACES
Authors: DEDIEU THOMAS
Published: December 2009

Self-rational maps of generic algebraic K3 surfaces are conjectured to be trivial. We relate this conjecture to a conjecture concerning the irreducibility of the universal Severi varieties parameterizing nodal curves of given genus and degree lying on some K3 surface. We also establish a number of numerical constraints satisfied by such nontrivial rational maps, that is of topological degree > 1.
Morphology-Based Segmentation Combination for Arabic Mention Detection
Authors: Benajiba Yassine , Zitouni Imed
Published: January 2010

The Arabic language has a very rich/complex morphology. Each Arabic word is composed of zero or more
prefixes
, one
stem
and zero or more
suffixes
. Consequently, the Arabic data is sparse compared to other languages such as English, and it is necessary to conduct word segmentation before any natural language processing task. Therefore, the word-segmentation step is worth a deeper study since it is a preprocessing step which shall have a significant impact on all the steps coming afterward. In this article, we present an Arabic mention detection system that has very competitive results in the recent Automatic Content Extraction (ACE) evaluation campaign. We investigate the impact of different segmentation schemes on Arabic mention detection systems and we show how these systems may benefit from more than one segmentation scheme. We report the performance of several mention detection models using different kinds of possible and known segmentation schemes for Arabic text: punctuation separation, Arabic Treebank, and morphological and character-level segmentations. We show that the combination of competitive segmentation styles leads to a better performance. Results indicate a statistically significant improvement when Arabic Treebank and morphological segmentations are combined.
Sphingosine 1-phosphate signaling is involved in skeletal muscle regeneration
Authors: Danieli-Betto Daniela , Peron Samantha , Germinario Elena , Zanin Marika , Sorci Guglielmo , Franzoso Susanna , Sandonà Dorianna , Betto Romeo
Published: December 2009

Sphingosine 1-phosphate (S1P) is a bioactive lipid known to control cell growth that was recently shown to act as a trophic factor for skeletal muscle, reducing the progress of denervation atrophy. The aim of this work was to investigate whether S1P is involved in skeletal muscle fiber recovery (regeneration) after myotoxic injury induced by bupivacaine. The postnatal ability of skeletal muscle to grow and regenerate is dependent on resident stem cells called satellite cells. Immunofluorescence analysis demonstrated that S1P-specific receptors S1P1 and S1P3 are expressed by quiescent satellite cells. Soleus muscles undergoing regeneration following injury induced by intramuscular injection of bupivacaine exhibited enhanced expression of S1P1 receptor, while S1P3 expression progressively decreased to adult levels. S1P2 receptor was absent in quiescent cells but was transiently expressed in the early regenerating phases only. Administration of S1P (50 μM) at the moment of myotoxic injury caused a significant increase of the mean cross-sectional area of regenerating fibers in both rat and mouse. In separate experiments designed to test the trophic effects of S1P, neutralization of endogenous circulating S1P by intraperitoneal administration of anti-S1P antibody attenuated fiber growth. Use of selective modulators of S1P receptors indicated that S1P1 receptor negatively and S1P3 receptor positively modulate the early phases of regeneration, whereas S1P2 receptor appears to be less important. The present results show that S1P signaling participates in the regenerative processes of skeletal muscle.
Acetylsalicylic acid enhances purinergic receptor-mediated outward currents in rat megakaryocytes
Authors: Young José P. , Beckerman Jacob , Vicini Stefano , Myers Adam
Published: December 2009

Purinergic receptor activation increases cytosolic Ca2+concentration in a fluctuating fashion, triggering oscillatory outward Ca2+-activated K+currents in rat megakaryocytes (MKs). Whole cell and nystatin-perforated patch-clamp techniques were used to analyze changes in ionic conductance in MK with acetylsalicylic acid (ASA), a cyclooxygenase-1 inhibitor and antithrombotic agent. MKs are a model for platelet reactivity, particularly in ASA treatment failure (ASA resistance). Freshly isolated MKs were incubated 30 min in the absence or presence of 1 mM ASA. Using a K+-rich internal solution, we recorded outward currents in response to 10 μM ATP, 10 μM ADP, and 5 μM 2-methyl-thio-ADP (2MeSADP) in the voltage-clamp mode. Agonist-induced currents decreased in amplitude over time, but this decline was attenuated by ASA in both continuous and repeated agonist challenge, indicating increased MK reactivity with ASA treatment. In separate experiments, heterologous desensitization was observed when MKs were stimulated with ADP after exposure to a thromboxane receptor agonist (U46619), indicating cross talk between thromboxane and purinergic pathways. Different cells, treated with ASA or MRS2179 (P2Y1 receptor antagonist), were stimulated with 2MeSADP. The dose-response curve was shifted to the left in both cases, suggesting increased MK reactivity. ASA also caused an increased interval between currents (delay). ASA attenuated desensitization of purinergic receptors and increased delay, again suggesting cross talk between purinergic and thromboxane pathways. These findings may be relevant to ASA resistance, because individual variations in sensitivity to the multiple effects of ASA on signaling pathways could result in insensitivity to its antiplatelet effects in some patients.
Intrinsic membrane properties of locus coeruleus neurons in Mecp2-null mice
Authors: Zhang Xiaoli , Cui Ningren , Wu Zhongying , Su Junda , Tadepalli Jyothirmayee S. , Sekizar Sowmya , Jiang Chun
Published: December 2009

Rett syndrome caused by mutations in methyl-CpG-binding protein 2 ( Mecp2) gene shows abnormalities in autonomic functions in which brain stem norepinephrinergic systems play an important role. Here we present systematic comparisons of intrinsic membrane properties of locus coeruleus (LC) neurons between Mecp2−/Y and wild-type (WT) mice. Whole cell current clamp was performed in brain slices of 3- to 4-wk-old mice. Mecp2−/Y neurons showed stronger inward rectification and had shorter time constant than WT cells. The former was likely due to overexpression of inward rectifier K+ (Kir)4.1 channel, and the latter was attributable to the smaller cell surface area. The action potential duration was prolonged in Mecp2−/Y cells with an extended rise time. This was associated with a significant reduction in the voltage-activated Na+ current density. After action potentials, >60% Mecp2−/Y neurons displayed fast and medium afterhyperpolarizations (fAHP and mAHP), while nearly 90% WT neurons showed only mAHP. The mAHP amplitude was smaller in Mecp2−/Y neurons. The firing frequency was higher in neurons with mAHP, and the frequency variation was greater in cells with both fAHP and mAHP in Mecp2−/Y mice. Small but significant differences in spike frequency adaptation and delayed excitation were found in Mecp2−/Y neurons. These results indicate that there are several electrophysiological abnormalities in LC neurons of Mecp2−/Y mice, which may contribute to the dysfunction of the norepinephrine system in Rett syndrome.
Accelerated Ca2+entry by membrane hyperpolarization due to Ca2+-activated K+channel activation in response to histamine in chondrocytes
Authors: Funabashi Kenji , Ohya Susumu , Yamamura Hisao , Hatano Noriyuki , Muraki Katsuhiko , Giles Wayne , Imaizumi Yuji
Published: December 2009

In articular cartilage inflammation, histamine release from mast cells is a key event. It can enhance cytokine production and matrix synthesis and also promote cell proliferation by stimulating chondrocytes. In this study, the functional impact of Ca2+-activated K+(KCa) channels in the regulation of intracellular Ca2+concentration ([Ca2+]i) in chondrocytes in response to histamine was examined using OUMS-27 cells, as a model of chondrocytes derived from human chondrosarcoma. Application of histamine induced a significant [Ca2+]irise and also membrane hyperpolarization, and both effects were mediated by the stimulation of H1receptors. The histamine-induced membrane hyperpolarization was attenuated to ∼50% by large-conductance KCa(BK) channel blockers, and further reduced by intermediate (IK) and small conductance KCa(SK) channel blockers. The tonic component of histamine-induced [Ca2+]irise strongly depended on the presence of extracellular Ca2+([Ca2+]o) and was markedly reduced by La3+or Gd3+but not by nifedipine. It was significantly attenuated by BK channel blockers, and further blocked by the cocktail of BK, IK, and SK channel blockers. The KCablocker cocktail also significantly reduced the store-operated Ca2+entry (SOCE), which was induced by Ca2+addition after store-depletion by thapsigargin in [Ca2+]ofree solution. Our results demonstrate that the histamine-induced membrane hyperpolarization in chondrocytes due to KCachannel activation contributes to sustained Ca2+entry mainly through SOCE channels in OUMS-27 cells. Thus, KCachannels appear to play an important role in the positive feedback mechanism of [Ca2+]iregulation in chondrocytes in the presence of articular cartilage inflammation.
Colesevelam improves insulin resistance in a diet-induced obesity (F-DIO) rat model by increasing the release of GLP-1
Authors: Shang Quan , Saumoy Monica , Holst Jens Juul , Salen Gerald , Xu Guorong
Published: January 2010

Bile acid sequestrants have been shown to lower glucose levels in patients with type 2 diabetes. To investigate how colesevelam (CL) HCl improves hyperglycemia, studies were conducted in diet-induced obesity (F-DIO) rats, which develop insulin resistance when fed a high-energy (high fat/high sucrose) diet (HE). The rats were fed HE; HE + 2% CL; HE + 0.02% SC-435 (SC), an apical sodium-dependent bile acid transporter inhibitor; and regular chow (controls). After 4 wk of treatment, both in the HE group and the SC + HE group, plasma glucose and insulin levels remained elevated compared with baseline values throughout an oral glucose tolerance test (OGTT). In contrast, in the CL + HE group, plasma glucose levels returned to baseline by the end of the test, and insulin peaked in 15–30 min and then returned to baseline. CL induced release of glucagon-like peptide-1 (GLP-1) because the area under the curve of plasma total GLP-1 in the CL + HE group was significantly greater than in the HE group during the OGTT. Bile acid concentrations in the portal blood did not decrease in the HE group but declined significantly both in the CL + HE and SC + HE groups with reduced farnesoid X receptor activation compared with controls. We concluded that CL reduces plasma glucose levels by improving insulin resistance in this rat model. It is unlikely that the improvement is attributable to decreased bile acid flux to the liver but is likely secondary to induced GLP-1 secretion, which improves insulin release.
The intestinal lymph fistula model—a novel approach to study ghrelin secretion
Authors: Tong Jenny , Tschöp Matthias H. , Aulinger Benedikt A. , Davis Harold W. , Yang Qing , Liu Jianhua , Gaylinn Bruce D. , Thorner Michael O. , D'Alessio David , Tso Patrick
Published: January 2010

The orexigenic hormone ghrelin is secreted from the stomach and has been implicated in the regulation of energy and glucose homeostasis. We hypothesized that ghrelin, like other gastrointestinal (GI) hormones, is present in intestinal lymph, and sampling this compartment would provide advantages for studying ghrelin secretion in rodents. Blood and lymph were sampled from catheters in the jugular vein and mesenteric lymph duct before and after intraduodenal (ID) administration of isocaloric Ensure, dextrin, or Liposyn meals or an equal volume of saline in conscious Sprague-Dawley rats. Total ghrelin levels were measured using an established radioimmunoassay. Acyl and des-acyl ghrelin were measured using two-site ELISA. Fasting ghrelin levels in lymph were significantly higher than in plasma (means ± SE: 3,307.9 ± 272.9 vs. 2,127.1 ± 115.0 pg/ml, P = 0.004). Postingestive acyl and des-acyl ghrelin levels were also significantly higher, whereas the ratio of acyl:des-acyl ghrelin was similar in lymph and plasma (0.91 ± 0.28 vs. 1.20 ± 0.36, P = 0.76). The principle enzymes responsible for deacylation of ghrelin were lower in lymph than in plasma. Following ID Ensure, maximum ghrelin suppression occurred at 2 h in lymph compared with at 1 h in plasma. The return of suppressed ghrelin levels to baseline was also delayed in lymph. Similarly, dextrin also induced significant suppression of ghrelin (two-way ANOVA: P = 0.02), whereas Liposyn did not ( P = 0.32). On the basis of these findings, it appears that intestinal lymph, which includes drainage from the interstitium of the GI mucosa, is enriched in ghrelin. Despite reduced deacylating activity in lymph, there is not a disproportionate amount of acyl ghrelin in this pool. The postprandial dynamics of ghrelin are slower in lymph than plasma, but the magnitude of change is greater. Assessing ghrelin levels in the lymph may be advantageous for studying its secretion and concentrations in the gastric mucosa.
Lactobacillus acidophilus stimulates the expression of SLC26A3 via a transcriptional mechanism
Authors: Raheja Geetu , Singh Varsha , Ma Ke , Boumendjel Redouane , Borthakur Alip , Gill Ravinder K. , Saksena Seema , Alrefai Waddah A. , Ramaswamy Krishnamurthy , Dudeja Pradeep K.
Published: January 2010

Clinical efficacy of probiotics in treating various forms of diarrhea has been clearly established. However, mechanisms underlying antidiarrheal effects of probiotics are not completely defined. Diarrhea is caused either by decreased absorption or increased secretion of electrolytes and solutes in the intestine. In this regard, the electroneutral absorption of two major electrolytes, Na+ and Cl−, occurs mainly through the coupled operation of Na+/H+ exchangers and Cl−/OH− exchangers. Previous studies from our laboratory have shown that Lactobacillus acidophilus (LA) acutely stimulated Cl−/OH− exchange activity via an increase in the surface levels of the apical anion exchanger SLC26A3 (DRA). However, whether probiotics influence SLC26A3 expression and promoter activity has not been examined. The present studies were, therefore, undertaken to investigate the long-term effects of LA on SLC26A3 expression and promoter activity. Treatment of Caco-2 cells with LA for 6–24 h resulted in a significant increase in Cl−/OH− exchange activity. DRA mRNA levels were also significantly elevated in response to LA treatment starting as early as 8 h. Additionally, the promoter activity of DRA was increased by more than twofold following 8 h LA treatment of Caco-2 cells. Similar to the in vitro studies, in vivo studies using mice gavaged with LA also showed significantly increased DRA mRNA (∼4-fold) and protein expression in the colonic regions as assessed by Western blot analysis and immunofluorescence. In conclusion, increase in DRA promoter activity and expression may contribute to the upregulation of intestinal electrolyte absorption and might underlie the potential antidiarrheal effects of LA.
Chronic physical activity mitigates cerebral hypoperfusion during central hypovolemia in elderly humans
Authors: Formes Kevin , Zhang Peizhen , Tierney Nancy , Schaller Frederick , Shi Xiangrong
Published: January 2010

This study sought to test the hypothesis that orthostasis-induced cerebral hypoperfusion would be less severe in physically active elderly humans (ACT group) than in sedentary elderly humans (SED group). The peak O2 uptake of 10 SED (67.1 ± 1.4 yr) and 9 ACT (68.0 ± 1.1 yr) volunteers was determined by a graded cycling exercise test (22.1 ± 1.2 vs 35.8 ± 1.3 ml·min−1·kg−1, P < 0.01). Baseline mean arterial pressure (MAP; tonometry) and middle cerebral arterial blood flow velocity ( VMCA; transcranial Doppler) were similar between the groups (SED vs. ACT group: 91 ± 3 vs. 87 ± 3 mmHg and 54.9 ± 2.3 vs. 57.8 ± 3.2 cm/s, respectively), whereas heart rate was higher and stroke volume (bioimpedance) was smaller in the SED group than in the ACT group. Central hypovolemia during graded lower body negative pressure (LBNP) was larger ( P < 0.01) in the ACT group than in the SED group. However, the slope of VMCA/LBNP was smaller ( P < 0.05) in the ACT group (0.159 ± 0.016 cm/s/Torr) than in the SED group (0.211 ± 0.008 cm/s/Torr). During LBNP, the SED group had a greater augmentation of cerebral vasomotor tone ( P < 0.05) and hypocapnia ( P < 0.001) compared with the ACT group. Baseline MAP variability and VMCA variability were significantly smaller in the SED group than in the ACT group, i.e., 0.49 ± 0.07 vs. 1.04 ± 0.16 (mmHg)2 and 1.06 ± 0.19 vs. 4.24 ± 1.59 (cm/s)2, respectively. However, transfer function gain, coherence, and phase between MAP and VMCA signals (Welch spectral estimator) from 0.08–0.18 Hz were not different between SED (1.41 ± 0.18 cm·s−1·mmHg−1, 0.63 ± 0.06 units, and 38.03 ± 6.57°) and ACT (1.65 ± 0.44 cm·s−1·mmHg−1, 0.56 ± 0.05 units, and 48.55 ± 11.84°) groups. We conclude that a physically active lifestyle improves the intrinsic mechanism of cerebral autoregulation and helps mitigate cerebral hypoperfusion during central hypovolemia in healthy elderly adults.
Immune regulation and vascular inflammation in genetic hypertension
Authors: Viel Emilie C. , Lemarié Catherine A. , Benkirane Karim , Paradis Pierre , Schiffrin Ernesto L.
Published: December 2009

Immune cells have been implicated in the pathogenesis of hypertension. We hypothesized that under the influence of chromosome (chr)2, T lymphocytes contribute to vascular inflammation in genetic salt-sensitive hypertension. Normotensive (Brown Norway), hypertensive (Dahl salt-sensitive), and consomic rats (SSBN2; in which chr2 has been transferred from Brown Norway to Dahl rats) were studied. Systolic blood pressure, measured by tail cuff, and aortic preproendothelin mRNA, measured by quantitative RT-PCR, were elevated in Dahl rats compared with Brown Norway rats and were reduced in SSBN2 rats compared with Dahl rats ( P < 0.01). Compared with Brown Norway rats, Dahl rats exhibited increased inflammatory markers and mediators such as nuclear translocation of the aortic p65 subunit of NF-κB as well as VCAM-1, ICAM-1, chemokine (C-C motif) receptor 5, and CD4 mRNA, all of which were reduced in SSBN2 rats. Aortic CD8 mRNA was equally increased in Dahl and SSBN2 rats relative to Brown Norway rats. CD4+ T cell infiltration in the aorta of SSBN2 rats was reduced compared with Dahl rats, whereas the aortic protein expression of Foxp3b and immunosuppressors transforming growth factor (TGF)-β1 and IL-10, the three markers associated with the regulatory T cell lineage, were enhanced in SSBN2 rats. Activation in vitro of T cells demonstrated that CD4+CD25+ and CD8+CD25+ cells (Tregs) produce IL-10 in SSBN2 rats. Thus, increased vascular inflammatory responses and hypertension in a genetic salt-sensitive hypertensive rodent model are reduced by transfer of chr2 from a normotensive strain, and this is associated with enhanced levels of immunosuppressive mediators.
Hemoglobin encapsulation in vesicles retards NO and CO binding and O2release when perfused through narrow gas-permeable tubes
Authors: Sakai Hiromi , Okuda Naoto , Sato Atsushi , Yamaue Tatsuya , Takeoka Shinji , Tsuchida Eishun
Published: January 2010

Intravenous administration of cell-free Hb induces vasoconstriction and circulatory disorders, presumably because of the intrinsic affinities to endogenous nitric oxide (NO) and carbon monoxide (CO) as vasorelaxation factors and because of the facilitated O2release that might induce autoregulatory vasoconstriction. We examined these gas reactions when Hb-containing solutions of four kinds were perfused through artificial narrow tubes at a practical Hb concentration (10 g/dl). Purified Hb solution, polymerized bovine Hb (PolyBHb), encapsulated Hb [Hb-vesicles (HbV), 279 nm], and red blood cells (RBCs) were perfused through a gas-permeable narrow tube (25 μm inner diameter) at 1 mm/s centerline velocity. The level of reactions was determined microscopically based on the visible-light absorption spectrum of Hb. When the tube was immersed in NO and CO atmospheres, both NO binding and CO binding of deoxygenated Hb (deoxy-Hb) and PolyBHb in the tube was faster than those of HbV and RBCs, and HbV and RBCs showed almost identical binding rates. When the tube was immersed in a N2atmosphere, oxygenated Hb and PolyBHb showed much faster O2release than did HbV and RBCs. PolyBHb showed a faster reaction than Hb because of the lower O2affinity of PolyBHb than Hb. The diffusion process of the particles was simulated using Navier-Stokes and Maxwell-Stefan equations. Results clarified that small Hb (6 nm) diffuses laterally and mixes rapidly. However, the large-dimension HbV shows no such rapid diffusion. The purely physicochemical differences in diffusivity of the particles and the resulting reactivity with gas molecules are one factor inducing biological vasoconstriction of Hb-based oxygen carriers.
Contribution of BKCa channels to local metabolic coronary vasodilation: effects of metabolic syndrome
Authors: Borbouse Léna , Dick Gregory M. , Payne Gregory A. , Payne Brittany D. , Svendsen Mark C. , Neeb Zachary P. , Alloosh Mouhamad , Bratz Ian N. , Sturek Michael , Tune Johnathan D.
Published: January 2010

This investigation was designed to examine the hypothesis that impaired function of coronary microvascular large-conductance Ca2+-activated K+ (BKCa) channels in metabolic syndrome (MetS) significantly attenuates the balance between myocardial oxygen delivery and metabolism at rest and during exercise-induced increases in myocardial oxygen consumption (MV̇o2). Studies were conducted in conscious, chronically instrumented Ossabaw swine fed a normal maintenance diet (11% kcal from fat) or an excess calorie atherogenic diet (43% kcal from fat, 2% cholesterol, 20% kcal from fructose) that induces many common features of MetS. Data were collected under baseline/resting conditions and during graded treadmill exercise before and after selective blockade of BKCa channels with penitrem A (10 μg/kg iv). We found that the exercise-induced increases in blood pressure were significantly elevated in MetS swine. No differences in baseline cardiac function or heart rate were noted. Induction of MetS produced a parallel downward shift in the relationship between coronary venous Po2 and MV̇o2 ( P < 0.001) that was accompanied by a marked release of lactate (negative lactate uptake) as MV̇o2 was increased with exercise ( P < 0.005). Inhibition of BKCa channels with penitrem A did not significantly affect blood pressure, heart rate, or the relationship between coronary venous Po2 and MV̇o2 in lean or MetS swine. These data indicate that BKCa channels are not required for local metabolic control of coronary blood flow under physiological (lean) or pathophysiological (MetS) conditions. Therefore, diminished function of BKCa channels does not contribute to the impairment of myocardial oxygen-supply demand balance in MetS.
LPA induces IL-6 secretion from aortic smooth muscle cells via an LPA1-regulated, PKC-dependent, and p38α-mediated pathway
Authors: Hao Feng , Tan Mingqi , Wu Daniel D. , Xu Xuemin , Cui Mei-Zhen
Published: January 2010

Lysophosphatidic acid (LPA) is a potent bioactive lysophospholipid. Accumulated evidence supports a role for LPA in inflammation. To profile LPA-induced cytokine production in vascular smooth muscle cells (SMCs), we used a cytokine antibody array system and found that LPA prominently induces the secretion of IL-6 and monocyte chemoattractant protein (MCP)-1 from human aortic SMCs (HASMCs). The mechanism by which LPA induces MCP-1 expression in SMCs has been previously reported. However, LPA induction of IL-6 secretion from vascular SMCs and its regulatory mechanism are unknown. The present study reveals that LPA induces the expression of IL-6 mRNA and protein in HASMCs as well as the secretion of IL-6 protein in a time-dependent manner. Our results demonstrate that LPA-specific receptor 1 (LPA1) mediates LPA-induced IL-6 secretion and that LPA induction of IL-6 is independent of the EGF receptor pathway. Our data further show that PKC-mediated p38 MAPK is responsible for the IL-6 secretion. Finally, small interfering RNA depletion experiments revealed that p38α is specifically responsible for the LPA-induced IL-6 secretion. The present study profiles the regulatory relationship between LPA and multiple cytokines in vascular SMCs for the first time, provides the first evidence that LPA upregulates IL-6 in vascular SMCs, and reveals the regulatory mechanism of LPA-induced IL-6 production in HASMCs. In light of the emerging roles of LPA and IL-6 in vascular inflammation, the understanding of the regulatory mechanism may contribute to the treatment and prevention of cardiovascular disorders.
A novel approach to analyze gene expression data demonstrates that the ΔF508 mutation in CFTR downregulates the antigen presentation pathway
Authors: Hampton Thomas H. , Stanton Bruce A.
Published: January 2010

Gene array studies comparing cystic fibrosis (CF) and non-CF genotypes should reveal factors that explain variability in CF lung disease progression, yielding insights that lead to improved CF care. To date, studies have reached conflicting conclusions, perhaps due to experimental differences and divergent statistical approaches. This review aims: 1) to summarize the findings of four recent gene studies comparing CF and non-CF genotypes, and 2) to reanalyze original data using a recently developed statistical approach, with the aim of identifying genes and paths consistently regulated by the CF genotype. We identified four studies evaluating the effect of the ΔF508-CFTR mutation on human airway epithelial cell gene expression, restricting our investigation to human airway epithelial cell studies whose data were accessible in NCBI's Gene Expression Omnibus or the European Bioinformatic Institute's ArrayExpress. Gene expression patterns showed consistent repression of MHC class I antigen presentation genes in CF human airway epithelia, suggesting a novel mechanistic explanation for poor clearance of viral and bacterial infections by CF patients. We also examined proinflammatory and NF-κB genes, whose induction is widely accepted as a hallmark of the CF genotype, but found little evidence of induction, consistent with a recent review (Machen TE, Am J Physiol Cell Physiol 291: C218–C230, 2006.). In conclusion, our analysis suggests that the CF genotype may impair immune function in airway epithelial cells but may not increase inflammation. Additional studies are required to determine whether MHC class I gene repression in CF reduces antigen presentation at the protein level and whether repression impairs immune function.
Regulation of acid signaling in rat pulmonary sensory neurons by protease-activated receptor-2
Authors: Gu Qihai , Lee Lu-Yuan
Published: December 2009

Airway acidification has been consistently observed in airway inflammatory conditions and is known to cause cardiorespiratory symptoms that are, at least in part, mediated through the activation of bronchopulmonary C fibers and the subsequent reflexes. Protease-activated receptor-2 (PAR2) is expressed in a variety of cells in the lung and airways and is believed to play a role in airway inflammation and hyperresponsiveness. This study was carried out to investigate the effect of PAR2 activation on the acid signaling in rat bronchopulmonary C-fiber sensory neurons. Our RT-PCR results revealed the expression of mRNAs for transient receptor potential vanilloid receptor 1 (TRPV1) and four functional acid-sensing ion channel (ASIC) subunits 1a, 1b, 2a, and 3 in these sensory neurons. Preincubation of SLIGRL-NH2, a specific PAR2-activating peptide, markedly enhanced the Ca2+ transient evoked by extracellular acidification. Pretreatment with PAR2 agonists significantly potentiated both acid-evoked ASIC- and TRPV1-like whole cell inward currents. Activation of PAR2 also potentiated the excitability of these neurons to acid, but not electrical stimulation. In addition, the potentiation of acid-evoked responses was not prevented by inhibiting either PLC or PKC nor was mimicked by activation of PKC. In conclusion, activation of PAR2 modulates the acid signaling in pulmonary sensory neurons, and the interaction may play a role in the pathogenesis of airway inflammatory conditions, where airway acidification and PAR2 activation can occur simultaneously.
Functional contribution of CXCR2 to lung injury after aspiration of acid and gastric particulates
Authors: Nemzek Jean A. , Abatan Omorodola , Fry Christopher , Mattar Aladdein
Published: January 2010

The effects of individual ELR+ CXC chemokines have been documented in experimental models of acid aspiration. However, aspiration lung injury would be influenced by the combined effects of these chemokines and other factors related to their function. Therefore, the role of the chemokine receptor CXCR2 was examined in lung injury induced by aspiration of acid and acid with gastric particulates. Anesthetized mice were given intratracheal injections of saline, acid solution, or acid containing gastric particles. Within 6 h, bronchoalveolar lavage fluid neutrophils and albumin increased relative to the severity of the insult. Immunohistochemistry and RT-PCR demonstrated striking increases in pulmonary expression of CXCR2 after aspiration. In CXCR2-deficient mice, neutrophil recruitment to airways was significantly reduced after aspiration of either acid or acid with particles. However, lung injury scores were unaffected in Ccr2−/− mice in the acid + particles group. Esterase-stained lung tissue demonstrated that focal aggregates of inflammatory cells contained neutrophils in the Ccr2−/− mice. These studies suggest CXCR2 and its ligands are dominant mediators of neutrophil recruitment to airways after aspiration. However, CXCR2-independent mechanisms recruit neutrophils into areas of cellular aggregation after aspiration of acidified gastric particulates.
Physical exercise accelerates reentrainment of human sleep-wake cycle but not of plasma melatonin rhythm to 8-h phase-advanced sleep schedule
Authors: Yamanaka Yujiro , Hashimoto Satoko , Tanahashi Yusuke , Nishide Shin-ya , Honma Sato , Honma Ken-ichi
Published: December 2009

Effects of timed physical exercise were examined on the reentrainment of sleep-wake cycle and circadian rhythms to an 8-h phase-advanced sleep schedule. Seventeen male adults spent 12 days in a temporal isolation facility with dim light conditions (<10 lux). The sleep schedule was phase-advanced by 8 h from their habitual sleep times for 4 days, which was followed by a free-run session for 6 days, during which the subjects were deprived of time cues. During the shift schedule, the exercise group ( n = 9) performed physical exercise with a bicycle ergometer in the early and middle waking period for 2 h each. The control group ( n = 8) sat on a chair at those times. Their sleep-wake cycles were monitored every day by polysomnography and/or weight sensor equipped with a bed. The circadian rhythm in plasma melatonin was measured on the baseline day before phase shift: on the 4th day of shift schedule and the 5th day of free-run. As a result, the sleep-onset on the first day of free-run in the exercise group was significantly phase-advanced from that in the control and from the baseline. On the other hand, the circadian melatonin rhythm was significantly phase-delayed in the both groups, showing internal desynchronization of the circadian rhythms. The sleep-wake cycle resynchronized to the melatonin rhythm by either phase-advance or phase-delay shifts in the free-run session. These findings indicate that the reentrainment of the sleep-wake cycle to a phase-advanced schedule occurs independent of the circadian pacemaker and is accelerated by timed physical exercise.
Follicle-stimulating hormone, interleukin-1, and bone density in adult women
Authors: Cannon Joseph G. , Cortez-Cooper Miriam , Meaders Eric , Stallings Judith , Haddow Sara , Kraj Barbara , Sloan Gloria , Mulloy Anthony
Published: December 2009

Recent studies have indicated that follicle-stimulating hormone (FSH) promotes bone loss. The present study tested the hypothesis that FSH enhances the activity of bone-resorbing cytokines [interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6], either by inducing their secretion or by altering their receptor expression. Thirty-six women between the ages of 20 and 50 were assessed for bone mineral density (BMD), reproductive hormone, cytokine ligand and soluble receptor concentrations, and surface expression of cytokine receptors on monocytes. In addition, isolated mononuclear cells were incubated in vitro with exogenous FSH. Univariate regression analyses indicated that BMD was inversely related to serum FSH ( r = −0.29 to −0.51, P = 0.03–0.001, depending upon the skeletal site). Physical activity and body composition were also identified as significant factors by multiple regressions. Exogenous FSH induced isolated cells to secrete IL-1β, TNF-α, and IL-6 in proportion to the surface expression of FSH receptors on the monocytes. Endogenous (serum) FSH concentrations correlated with the circulating concentrations of these cytokines. None of these individual cytokines was related to BMD, but the IL-1β to IL-1 receptor antagonist (IL-1Ra) ratio was inversely related to BMD ( r = −0.53, P = 0.002) in all but the most physically active women, who had significantly lower expression of IL-1 type I receptors relative to type II (decoy receptors, P = 0.01). Physical activity also correlated positively with secretion of inhibitory soluble IL-1 receptors ( r = 0.53, P = 0.003). Moreover, IL-1Ra correlated strongly with percent body fat ( r = 0.66, P < 0.0001). These results indicate that BMD is related to FSH concentration, physical activity, and body composition. Although each of these factors likely has direct effects on bone, the present study suggests that each may also influence BMD by modulating the activity of the osteoresorptive cytokine IL-1β.
A SLC4-like anion exchanger from renal tubules of the mosquito (Aedes aegypti): evidence for a novel role of stellate cells in diuretic fluid secretion
Authors: Piermarini Peter M. , Grogan Laura F. , Lau Kenneth , Wang Li , Beyenbach Klaus W.
Published: December 2009

Transepithelial fluid secretion across the renal (Malpighian) tubule epithelium of the mosquito ( Aedes aegypti ) is energized by the vacuolar-type (V-type) H+-ATPase and not the Na+-K+-ATPase. Located at the apical membrane of principal cells, the V-type H+-ATPase translocates protons from the cytoplasm to the tubule lumen. Secreted protons are likely to derive from metabolic H2CO3, which raises questions about the handling of HCO3−by principal cells. Accordingly, we tested the hypothesis that a Cl/HCO3anion exchanger (AE) related to the solute-linked carrier 4 (SLC4) superfamily mediates the extrusion of HCO3−across the basal membrane of principal cells. We began by cloning from Aedes Malpighian tubules a full-length cDNA encoding an SLC4-like AE, termed AeAE. When expressed heterologously in Xenopus oocytes, AeAE is both N- and O-glycosylated and mediates Na+-independent intracellular pH changes that are sensitive to extracellular Cl−concentration and to DIDS. In Aedes Malpighian tubules, AeAE is expressed as two distinct forms: one is O-glycosylated, and the other is N-glycosylated. Significantly, AeAE immunoreactivity localizes to the basal regions of stellate cells but not principal cells. Concentrations of DIDS that inhibit AeAE activity in Xenopus oocytes have no effects on the unstimulated rates of fluid secretion mediated by Malpighian tubules as measured by the Ramsay assay. However, in Malpighian tubules stimulated with kinin or calcitonin-like diuretic peptides, DIDS reduces the diuretic rates of fluid secretion to basal levels. In conclusion, Aedes Malpighian tubules express AeAE in the basal region of stellate cells, where this transporter may participate in producing diuretic rates of transepithelial fluid secretion.