bluuebunny/crossref_metadata_2025 huggingface dataset:
Roles of NCX and PMCA in Basolateral Calcium Export Associated with Mineralization Cycles and Cold Acclimation in Crayfish
Authors: WHEATLY M. G. , GAO Y. , STINER L. M. , WHALEN D. R. , NADE M. , VIGO F. , GOLSHANI A. E.
Published: April 2007

Abstract:  Basolateral Na+/Ca2+ exchanger (NCX) and plasma membrane Ca2+ ATPase (PMCA) are the primary transmembrane proteins that export calcium (Ca2+) from cells. In our lab we use a nonmammalian animal model, the freshwater crayfish, to study cellular Ca2+ regulation. Two experimental conditions are employed to effect Ca2+ dyshomeostasis: (a) in the postmolt stage of the crustacean molting cycle increased unidirectional Ca2+ influx associated with cuticular mineralization is accompanied by elevated basolateral Ca2+ export (compared with intermolt Ca balance); and (b) exposure of the poikilothermic crayfish to cold acclimation (4°C) causes influx of Ca2+ into cells, which is compensated by increased basolateral Ca2+ export (compared with exposure to 23°C). This study compares expression of both NCX and PMCA mRNA (real‐time PCR) and protein (Western) in both epithelial (kidney) and nonepithelial tissue (tail muscle) during elevated basolateral Ca2+ export. Both experimental treatments produced increases in NCX and PMCA expression (mRNA and protein) in both tissues. Mineralization produced greater upregulation of mRNA in kidney than in tail, whereas cold acclimation yielded comparable increases in both tissues. Protein expression patterns were generally confirmatory of real‐time PCR data although expression changes were less pronounced. Both experimental treatments appear to increase basolateral Ca2+ export.
Redox Modulation of the Apoptogenic Activity of Thapsigargin
Authors: CERELLA CLAUDIA , COPPOLA SIMONA , D'ALESSIO MARIA , DE NICOLA MILENA , MAGRINI ANDREA , BERGAMASCHI ANTONIO , GHIBELLI LINA
Published: April 2007

Abstract: Thapsigargin (THG), a selective inhibitor of endoplasmic reticulum (ER) Ca2+‐ATPases, causes the rapid emptying of ER Ca2+; in some cell types, this is accompanied by apoptosis, whereas other cells maintain viability. In order to understand the molecular determinants of such a different behavior, we explored the role of oxygen versus nitrogen radicals, by analyzing the apoptogenic ability of THG in the presence of inhibitors of glutathione or nitric oxide (NO) synthesis, respectively. We observed that oxygen radicals play a sensitizing role whereas nitrogen radicals prevent THG‐dependent apoptosis, showing that the apoptogenic effect of THG is redox sensitive.
Distinct Phenotypes among Plasma Membrane Ca2+‐ATPase Knockout Mice
Authors: PRASAD VIKRAM , OKUNADE GBOLAHAN , LIU LI , PAUL RICHARD J. , SHULL GARY E.
Published: April 2007

Abstract:  Ca2+ gradients across the plasma membrane, required for Ca2+ homeostasis and signaling, are maintained in part by plasma membrane Ca2+‐ATPase (PMCA) isoforms 1–4. Gene targeting has been used to analyze the functions of PMCA1, PMCA2, and PMCA4 in mice. PMCA1 null mutant embryos die during the preimplantation stage, and loss of a single copy of the PMCA1 gene contributes to apoptosis in vascular smooth muscle. PMCA2 deficiency in sensory hair cells of the inner ear causes deafness and balance defects, most likely by affecting both intracellular Ca2+ and extracellular Ca2+ in the endolymph. PMCA2 is required for viability of certain neurons, consistent with a major role in maintenance of intracellular Ca2+. Surprisingly, loss of PMCA2 in lactating mammary glands causes a sharp reduction in milk Ca2+, consistent with a macrocalcium secretory function. Although PMCA4 is widely expressed and is the most abundant isoform in some tissues, null mutants appear healthy. However, male PMCA4 null mutants are infertile due to a failure of hyperactivated sperm motility resulting from the absence of PMCA4 in the sperm tail, and Ca2+ signaling in B lymphocytes, involving interactions between PMCA4, CD22, and the tyrosine phosphatase SHP‐1, is defective. Studies of bladder smooth muscle from PMCA4 null mutants and PMCA1 heterozygous mice suggest that PMCA1 and PMCA4 play different roles in smooth muscle contractility, with PMCA1 contributing to overall Ca2+ clearance and PMCA4 being required for carbachol‐stimulated contraction. These phenotypes indicate that PMCA1 serves essential housekeeping functions, whereas PMCA4 and particularly PMCA2 serve more specialized physiological functions.
Involvement of Na+/Ca2+ Exchanger Type‐1 in Ischemia‐Induced Neovascularization in the Mouse Hindlimb
Authors: MATSUI YUKIKO , KITA SATOMI , KATSURAGI TAKESHI , KOMURO ISSEI , IWAMOTO TAKAHIRO , OHJIMI HIROYUKI
Published: April 2007

Abstract:  The Na+/Ca2+ exchanger (NCX) is considered to be involved in endothelial nitric oxide (NO) production and endothelium‐dependent vasorelaxation, but little is known about the physiological and pathological roles of endothelial NCX in these processes. We examined the role of NCX1 in neovascularization in mice with hindlimb ischemia. Unilateral hindlimb ischemia was induced surgically in wild‐type and heterozygous NCX1 knockout mice (NCX1+/−) mice. We found that in NCX1+/− mice, blood flow recovery was significantly augmented compared with that in wild‐type mice. NG‐nitro‐L‐arginine methyl ester treatment eliminated enhanced angiogenesis observed in NCX1+/− mice. These results suggest that NCX1 is involved in eNOS‐dependent angiogenesis.
Shedding Light on the Na+/Ca2+ Exchanger
Authors: OTTOLIA MICHELA , JOHN SCOTT , XIE YI , REN XIAOYAN , PHILIPSON KENNETH D.
Published: April 2007

Abstract:  The Na+/Ca2+ exchanger (NCX) regulates cardiac contractility by adjusting the amount of Ca2+ inside myocytes. NCX accomplishes this by using the electrochemical gradient of Na+: during each cycle three Na+ ions enter the cell and one Ca2+ ion is extruded against its gradient. In addition to being transported, cytoplasmic Na+ and Ca2+ ions also regulate exchanger activity. The physiological relevance and molecular processes underlying ionic regulation remain unclear. Also unresolved are the events that regulate NCX trafficking to the membrane and its oligomeric state. This is essential information to interpret structure–function data. The full‐length exchanger was fused to both CFP and YFP, creating active fluorescent exchangers used in FRET experiments to assess both conformational changes associated with ionic regulation and the oligomeric state of NCX. Electrophysiological characterization demonstrates that these constructs behave similarly to the wild‐type (WT) exchanger. We have been able for the first time to monitor conformational changes of the exchanger Ca2+‐binding site

in vivo

. These studies provide a better understanding of the molecular properties of the NCX.
The Regulation of the Na/Ca Exchanger and Plasmalemmal Ca2+ ATPase by Other Proteins
Authors: RUKNUDIN ABDUL M. , LAKATTA EDWARD G.
Published: April 2007

Abstract:  Na/Ca exchanger (NCX) and plasma membrane Ca2+ ATPase are the Ca2+ efflux mechanisms known in mammalian cells. NCX is the main transporter to efflux intracellular Ca2+ in the heart. NCX protein contains nine putative transmembrane domains and a large intracellular loop joining two sets of the transmembrane domains. The intracellular loop regulates the activity of the NCX by interacting with other proteins and nonprotein factors, such as ions, PIP2. Several proteins that are associated with NCX have been identified recently. Similarly, plasmalemmal Ca2+ ATPase (PMCA) has 10 putative transmembrane domains, and the C‐terminal intracellular region inhibits transporter activity. There are several proteins associated with PMCA, and the roles of the associated proteins of PMCA vary from specific localization to involving PMCA in signal transduction. Elucidation of structural and functional roles played by these associated proteins of NCX and PMCA will provide opportunities to develop drugs of potential therapeutic value.
The Squid Preparation as a General Model for Ionic and Metabolic Na+/Ca2+Exchange Interactions
Authors: DIPOLO R. , BEAUGÉ L.
Published: April 2007

Abstract: We propose an integrated kinetic model for the squid nerve Na+/Ca2+exchanger based on experimental evidences obtained in dialyzed axons. This model satisfactorily explains the interrelationship between ionic (Na+i–H+i–Ca2+i) and metabolic (ATP, phosphoarginine (PA)) regulation of the exchanger. Data in dialyzed axons show that the Cai‐regulatory site located in the large intracellular loop plays a central role in the modulation by ATP by antagonizing the inhibitory Na+i–H+isynergism. We have used the Nao/Naiexchange mode to unequivocally measure the affinity of the Cai‐regulatory site. This allowed us to separate Cai‐regulatory from Cai‐transport sites and to estimate their respective affinities. In this work we show for the first time that under conditions of saturation of the Cai‐regulatory site (10 μM Ca2+i, pHi8.0), ATP have no effect on the Cai‐transport site. In addition, we have expanded our equilibrium kinetic model of ionic and metabolic interactions to a complete exchange cycle (circular model). This model, in which the Cai‐regulatory site plays a central role, accounts for the decrease in Naiinactivation, at high pHi, high Ca2+i,and MgATP. Furthermore, the model also predicts the net Ca2+movements across the exchanger based on the exchanger complexes redistribution both during physiological and pathological conditions (ischemia).
Involvement of the Potassium‐Dependent Sodium/Calcium Exchanger Gene Product NCKX2 in the Brain Insult Induced by Permanent Focal Cerebral Ischemia
Authors: CUOMO ORNELLA , PIGNATARO GIUSEPPE , GALA ROSARIA , BOSCIA FRANCESCA , TORTIGLIONE ANNA , MOLINARO PASQUALE , RENZO GIANFRANCO DI , LYTTON JONATHAN , ANNUNZIATO LUCIO
Published: April 2007

Abstract:  Sodium/calcium exchangers are neuronal plasma membrane transporters, which by coupling Ca2+ and Na+ fluxes, may play a relevant role in brain ischemia. The exchanger gene superfamily comprises two arms: the K+‐independent (NCX) and K+‐dependent (NCKX) exchangers. In the brain, three different NCX (NCX1, NCX2, NCX3) and three NCKX (NCKX2, NCKX3, NCKX4) family members have been described. Up to now, no sutides about the role played by NCKX proteins in cerebral ischemia have been published. The aim of the present study was to investigate the role of NCKX2 in an in vivo model of permanent middle cerebral artery occlusion (pMCAO). The role of this protein in the development of ischemic damage was assessed by knocking‐down its expression with an antisense oligodeoxynucleotide (AS‐ODN), intracerebroventricularly infused by an osmotic minipump for 48 h, starting from 24 h before pMCAO. The results showed that NCKX2 knocking‐down by using antisense strategy increased the extent of the ischemic lesion. The results of this study suggest that NCKX2 could exert a neuroprotective effect during ischemic injury.
The Na+/Ca2+ Exchanger Isoform 3 (NCX3) but Not Isoform 2 (NCX2) and 1 (NCX1) Singly Transfected in BHK Cells Plays a Protective Role in a Model of in Vitro Hypoxia
Authors: SECONDO AGNESE , STAIANO ILARIA ROSARIA , SCORZIELLO ANTONELLA , SIRABELLA ROSSANA , BOSCIA FRANCESCA , ADORNETTO ANNAGRAZIA , CANZONIERO LORELLA MARIA TERESA , DI RENZO GIANFRANCO , ANNUNZIATO LUCIO
Published: April 2007

Abstract:  Chemical hypoxia produces depletion of ATP, intracellular Ca2+ overload, and cell death. The role of Na+/Ca2+ exchanger (NCX), the major plasma membrane Ca2+ extruding system, has been explored in chemical hypoxia using BHK cells stably transfected with the three mammalian NCX isoforms: NCX1, NCX2, and NCX3. Here we report that the three isoforms show similar activity evaluated as [Ca2+]i increase evoked by Na+‐free medium exposure in Fura‐2‐loaded single cells and NCX3 transfected cells are less vulnerable to chemical hypoxia compared to NCX1‐ and NCX2‐transfected cells, suggesting that NCX3 could play a more relevant protective role during chemical hypoxia.
Regulation of Ncx1 Gene Expression in the Normal and Hypertrophic Heart
Authors: MENICK DONALD R. , RENAUD LUDIVINE , BUCHHOLZ AVERY , MÜLLER JOACHIM G. , ZHOU HONGMING , KAPPLER CHRISTIANA S. , KUBALAK STEVEN W. , CONWAY SIMON J. , XU LIN
Published: April 2007

Abstract:  The Na+/Ca2+ exchanger (NCX1) is crucial in the regulation of [Ca2+]i in the cardiac myocyte. The exchanger is upregulated in cardiac hypertrophy, ischemia, and failure. This upregulation can have an effect on Ca2+ transients and possibly contribute to diastolic dysfunction and an increased risk of arrhythmias. Studies from both in vivo and in vitro model systems have provided an initial skeleton of the potential signaling pathways that regulate the exchanger during development, growth, and hypertrophy. The Ncx1 gene is upregulated in response to α‐adrenergic stimulation. We have shown that this is via p38α activation of transcription factors binding to the Ncx1 promotor at the –80 CArG element. Interestingly, most of the elements, including the CArG element, which we have demonstrated to be important for regulation of Ncx1 expression are in the proximal 184 bp of the promotor. Using a transgenic mouse, we have shown that the proximal 184 bp is sufficient for expression of reporter genes in adult cardiomyocytes and for the correct spatiotemporal pattern of Ncx1 expression in development but not for upregulation in response to pressure overload.
Thyroid Dysfunction and Effects on Coagulation and Fibrinolysis: A Systematic Review
Authors: Squizzato A. , Romualdi E. , Büller H. R. , Gerdes V. E. A.
Published: April 2007

Context: Various changes in the coagulation-fibrinolytic system have been described in patients with an excess or deficiency of thyroid hormones. The purpose of this systematic review is to summarize the effects of hyperthyroidism and hypothyroidism on these systems.

Evidence Acquisition: All published case-control or interventional cohort studies that evaluated the effects of hyperthyroidism and hypothyroidism on the coagulation-fibrinolytic system in vivo were identified by a computer-assisted search of the MEDLINE and EMBASE electronic databases. A scoring system was used to divide studies into three quality categories: high, medium, and low quality.

Evidence Synthesis: A total of 36 papers were included. Because in several papers more than one case-control study or both a case-control and intervention study were described, a total of 39 case-control studies and 24 interventional cohort studies were analyzed. No high-quality study was identified. Three (7.7%) case-control and eight (33.3%) cohort studies were of medium quality. A total of 19 tests were investigated in the medium-quality studies. These tests revealed a hypocoagulable state for overt hypothyroidism and a hypercoagulable state for overt hyperthyroidism.

Conclusions: This analysis confirmed that clinically overt hyperthyroidism and hypothyroidism modify the coagulation-fibrinolytic balance, indicating that thyroid hormone excess or deficit is the probable main pathophysiological mechanism. Patients with overt hypothyroidism and overt hyperthyroidism appear to have an increased risk of bleeding and of thrombosis, respectively.
Na,K-ATPase α2 and Ncx4a regulate zebrafish left-right patterning
Authors: Shu Xiaodong , Huang Jie , Dong Yuan , Choi Jayoung , Langenbacher Adam , Chen Jau-Nian
Published: April 2007

A conserved molecular cascade involving Nodal signaling that patterns the laterality of the lateral mesoderm in vertebrates has been extensively studied, but processes involved in the initial break of left-right (LR)symmetry are just beginning to be explored. Here we report that Na,K-ATPaseα2 and Ncx4a function upstream of Nodal signaling to regulate LR patterning in zebrafish. Knocking down Na,K-ATPase α2 and Ncx4a activity in dorsal forerunner cells (DFCs), which are precursors of Kupffer's vesicle(KV), is sufficient to disrupt asymmetric gene expression in the lateral plate mesoderm and randomize the placement of internal organs, indicating that the activity of Na,K-ATPase α2 and Ncx4a in DFCs/KV is crucial for LR patterning. High-speed videomicroscopy and bead implantation experiments show that KV cilia are immobile and the directional fluid flow in KV is abolished in Na,K-ATPase α2 and Ncx4a morphants, suggesting their essential role in KV ciliary function. Furthermore, we found that intracellular Ca2+ levels are elevated in Na,K-ATPase α2 and Ncx4a morphants and that the defects in ciliary motility, KV fluid flow and placement of internal organs induced by their knockdown could be suppressed by inhibiting the activity of Ca2+/calmodulin-dependent protein kinase II. Together, our data demonstrate that Na,K-ATPase α2 and Ncx4a regulate LR patterning by modulating intracellular calcium levels in KV and by influencing cilia function, revealing a previously unrecognized role for calcium signaling in LR patterning.
Information processing of food cues in overweight and normal weight adolescents
Authors: Soetens Barbara , Braet Caroline
Published: April 2007

Objectives. Based on cognitive theory (CT), the aim of this study is to investigate the cognitive processing of food cues in clinically overweight adolescents.

Design. An experimental design with performance‐based measures.

Methods. Eighty‐seven (45 overweight, 42 normal weight) adolescents between the ages of 12 and 18 years were examined. All completed an imbedded word task (IWT), containing high caloric food words and matched control words, as a measure of attention interference. A free‐recall task was used to detect explicit memory biases. To study the effects of cognitive avoidance, participants were instructed to suppress thoughts about food or merely to monitor them, prior to completing the IWT and memory task.

Results. No evidence was found for interference in the attention processing of food cues. Also, no effects of thought suppression were found. However, consistent with hypotheses, the overweight adolescents did show an explicit memory bias for food stimuli, not due to a more general negative evaluation of food words.

Conclusion. The results provide at least partial support for the applicability of CT to adolescent obesity. The study was the first to reveal a memory bias for high caloric food cues in overweight youngsters, which may well reflect a later‐stage activation of food‐related schemata. These may play a role in food‐related preoccupations and overeating. The existence of an early‐stage attention bias is less clear and requires further investigation.
Using the demand–control model of job strain to predict caregiver burden and caregiver satisfaction in the informal caregivers of heart failure patients
Authors: Molloy Gerard J. , Johnston Derek W. , Johnston Marie , Gao Chuan , Witham Miles D. , Struthers Allan D. , McMurdo Marion E. T.
Published: April 2007

Objectives The demand–control (D–C) model of job strain has generated a considerable body of empirical support in predicting psychological health outcomes in the context of work. This study aimed to extend previous work using the D–C model of job strain to predict caregiver burden and satisfaction in the informal caregivers of patients with heart failure.

Design and method Data were gathered from 60 caregiver/patient dyads in a cross‐sectional design. Patients with chronic stable heart failure were recruited from out‐patient clinics. The dependent variables were caregiver burden and satisfaction. Demand and control were measured using both patient‐ and caregiver‐derived measures.

Results The D–C model accounted for 15 and 19% of the variance in caregiver burden, after controlling for age, gender and relationship to the patient. Lower control was associated with higher burden. The D–C model did not predict caregiver satisfaction.

Conclusion The D–C model was associated with caregiver burden, but not satisfaction in caregivers, with control being the dominant predictor. Research linking the theory and findings from job strain and informal caregiving studies may elucidate both fields of research.

Using the demand–control model of job strain to predict caregiver burden and caregiver satisfaction in the informal caregivers of heart failure patients.
Radio and the documentary imagination: thirty years of experiment, innovation, and revelation
Authors: Madsen Virginia M
Published: April 2007

A renaissance occurred from the late 1960s in the art of documentary and feature production in radio, especially from within the major public broadcasters of Europe. Surprisingly, the pioneering work of this little commented-upon group of accomplished artisans finds its most immediate
parallels not in radio but film culture, particularly in the auteur, nouvelle vague and cinma-vrit movements of the time. The new acoustic documentary-feature project suggests a radio new wave: a new art of wild sound recording freed from script and studio, and made possible by the advent
of portable recorders, microphones and a strong infusion of 1968 zeitgeist.
An Orally Active Catalytic Metalloporphyrin Protects against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine NeurotoxicityIn Vivo
Authors: Liang Li-Ping , Huang Jie , Fulton Ruth , Day Brian J. , Patel Manisha
Published: April 2007

Parkinson's disease (PD) is an age-related neurodegenerative disease in which the role of reactive oxygen species (ROS) is strongly implicated. The presence of oxidative stress has been detected in human and experimental PD using both direct and indirect indices. Scavenging ROS is, therefore, an important therapeutic avenue for the treatment of PD. Manganic porphyrins are catalytic antioxidants that scavenge a wide range of ROS. In this study, we tested the therapeutic effects of a compound [5,15-bis(methoxycarbonyl)-10,20-bis-trifluoromethyl-porphyrinato manganese (III) chloride (AEOL11207)] belonging to a new generation of lipophilic manganic porphyrins for neuroprotection and oral bioavailability in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of parkinsonism. Groups of adult C57BL/6 mice were administered MPTP with varying subcutaneous or oral dosing regimens of AEOL11207. Neurotoxicity was assessed by measurement of striatal dopamine levels and quantification of tyrosine hydroxylase-positive neurons in the substantial nigrapars compactaone week after the first dose of MPTP. Glutathione depletion, lipid peroxidation, and 3-nitrotyrosine (3-NT) formation were measured as indicators of oxidative stress in the ventral midbrainin vivo. AEOL11207 administered either by subcutaneous or oral routes protected against MPTP-induced dopamine depletion in the striatum as well as dopaminergic neuronal loss, glutathione depletion, lipid peroxidation, and 3-NT formation in the ventral midbrain. Neuroprotection correlated with brain metalloporphyrin concentrations. This is the first demonstration of neuroprotection by an orally active catalytic antioxidant in the MPTP mouse model and suggests its potential clinical utility for the treatment of chronic neurodegenerative diseases such as PD.
Netrin-1/DCC Signaling in Commissural Axon Guidance Requires Cell-Autonomous Expression of Heparan Sulfate
Authors: Matsumoto Yoshihiro , Irie Fumitoshi , Inatani Masaru , Tessier-Lavigne Marc , Yamaguchi Yu
Published: April 2007

There is increasing evidence that heparan sulfate (HS) plays an essential role in various axon guidance processes. These observations, however, have not addressed whether HS is required cell autonomously as an axonal coreceptor or as an environmental factor that modulates the localization of guidance molecules in the terrain in which growing axons navigate. Here we demonstrate that netrin-1-mediated commissural axon guidance requires cell-autonomous expression of HS in commissural neuronsin vivo. We used theWnt1 –Cretransgene to drive region-specific ablation ofExt1, which encodes an enzyme essential for HS synthesis, in the dorsal part of the spinal cord. Remarkably,Wnt1–Cre-mediated ablation ofExt1causes commissural axon pathfinding defects that share similarities with those ofNetrin-1-deficient andDCC(deleted in colorectal cancer)-deficient mice. NeitherExt1-deficient dorsal spinal cord explants nor wild-type explants in which HS expression was ablated could extend axons in response to netrin-1. Intracellular signaling downstream of netrin-1 and DCC was defective inExt1-deficient commissural neurons and in DCC-transfected HEK293T cells from which HS was removed. These results demonstrate that the expression of HS by commissural neurons is essential for these neurons to transduce netrin-1 signals, thus providing evidence for a cell-autonomous role of HS in netrin-1/DCC-mediated axon guidance.
The Synthesis of Rhythms: Form, Ideology, and the “Augurs of Spring”
Authors: CODE DAVID J.
Published: April 2007

At the time of the premiere of The Rite of Spring, Stravinsky suggestively described its first dance, “Augurs of Spring,” as a “synthesis of rhythms.” Later, he characterized the whole ballet as an “architectonic” work. Richard Taruskin, in arguing for the ballet's overall aesthetic of “primitive simplicity,” polemically rejects this latter adjective as a typical formalist lie. But detailed analysis demonstrates the architectonic intricacy of the rhythmic synthesis in “Augurs” alone. Not only are the composer's labors toward such local intricacy clearly evident in the sketches, but a dialectical account of formalism and immediacy in this one dance confirms both the documented “neonationalist” background and initial reception, while pointing to a finer understanding of this ballet's position in the stylistic development of Stravinsky's Russian period.
The Place of Musica in Medieval Classifications of Knowledge
Authors: DYER JOSEPH
Published: April 2007

Medieval classifications of knowledge (divisiones scientiarum) were created to impose order on the ever-expanding breadth of human knowledge and to demonstrate the interconnectedness of its several parts. In the earlier Middle Ages the trivium and the quadrivium had sufficed to circumscribe the bounds of secular learning, but the eventual availability of the entire Aristotelian corpus stimulated a reevaluation of the scope of human knowledge. Classifications emanating from the School of Chartres (the Didascalicon of Hugh of St. Victor and the anonymous Tractatus quidam) did not venture far beyond Boethius, Cassiodorus, and Isidore of Seville. Dominic Gundissalinus (fl. 1144–64), a Spaniard who based parts of his elaborate analysis of music on Al-Fārābī, attempted to balance theory and practice, in contradistinction to the earlier mathematical emphasis. Aristotle had rejected musica mundana, and his natural science left little room for a musica humana based on numerical proportion. Consequently, both had to be reinterpreted.

Robert Kilwardby's De ortu scientiarum (ca. 1250) sought to integrate the traditional Boethian treatment of musica with an Aristotelian perspective. Responding to the empirical emphasis of Aristotle's philosophy, Kilwardby focused on music as audible phenomenon as opposed to Platonic “sounding number.” Medieval philosophers were reluctant to assign (audible) music to natural science or to place it among the scientie mechanice. One solution argued that music, though a separate subiectum suitable for philosophical investigation, was subalternated to arithmetic. Although drawing its explanations from that discipline, it nevertheless had its own set of “rules” governing its proper activity.

Thomas Aquinas proposed to resolve the conflict between the physicality of musical sound and abstract mathematics through the theory of scientie medie. These stood halfway between speculative and natural science, taking their material objects from physical phenomena but their formal object from mathematics. Still, Thomas defended the superiority of the speculative tradition by asserting that scientie medie “have a closer affinity to mathematics” (magis sunt affines mathematicis) than to natural science.
Dehydroepiandrosterone improves murine osteoblast growth and bone tissue morphometry via mitogen-activated protein kinase signaling pathway independent of either androgen receptor or estrogen receptor
Authors: Wang Ling , Wang Yu-Dong , Wang Wen-Jun , Zhu Ying , Li Da-Jin
Published: April 2007

Dehydroepiandrosterone (DHEA) may be a promising agent for postmenopausal osteoporosis (PMO), but its mechanism to modulate osteoblasts (OBs) is yet to be explained. To elucidate the effects of DHEA treatment on the ovariectomized (OVX) mice and its mechanisms, we evaluated the morphology of mice bone tissue and expression of proliferating cell nuclear antigen (PCNA) in the vertebrae-derived OB after having treated the OVX animals with DHEA. The results showed that DHEA administration increased the expression of PCNA in OB and changed the bone tissue morphometry of the PMO model. To further investigate this mechanism, the OB was isolated from neonatal mice calvariae by the enzyme-digested assay, exposed to DHEA, and then analyzed for ultrastructure, DNA content, early apoptotic cells, and phosphorylation of extracellular signal-regulated kinase 1/2. It was found that DHEA promoted proliferation and inhibited apoptosis of OB significantly, via mitogen-activated protein kinase signaling pathway independent of either androgen receptor or estrogen receptor, suggesting that it may exert roles via a DHEA-specific receptor directly, not by way of conversion to androgens or estrogens.
Sp1 and Sp3 regulate glucokinase gene transcription in the liver of gilthead sea bream (Sparus aurata)
Authors: Egea M , Metón I , Baanante I V
Published: April 2007

To better understand the transcriptional machinery that governs glucokinase (GCK) expression, we have cloned and characterized the proximal promoter region of GCK from gilthead sea bream (Sparus aurata). The 5′-flanking region of GCK was isolated by chromosome walking. SMART RACE-PCR allowed us to locate the transcription start site 98 bp (bp) upstream from the translational start. Transfection analysis in HepG2 cells revealed the presence of a functional promoter in the 1397 bp 5′-flanking isolated fragment (positions −1321 to +76 relative to the transcription start site). Sequential 5′-deletion analysis indicated a core functional promoter for basal transcription within the 288 bp upstream from the transcription start site. Transient transfection experiments performed in HepG2 cells and electrophoretic mobility shift assays denoted that Sp1 binds and transactivates GCK promoter, whereas Sp3 repressed Sp1-mediated activation of GCK by competing for the same binding site. Mutations in the Sp binding site completely abolished the enhancing effect of Sp1. Treatment with insulin stimulated GCK expression, and increased Sp1 levels in S. aurata liver. We propose a new mechanism that involves Sp1 and Sp3 to mediate insulin activation of GCK transcription.
Briefing: New register for security engineers
Authors: Hay Alec
Published: April 2007

Civil engineers involved with the design and provision of security measures can now apply to be ‘Registered Security Engineers’. Secretary Alec Hay introduces the newly formed Register of Security Engineers and Specialists, which is administered by ICE.
Research: the hidden power of UK construction
Authors: Clarke Barry
Published: April 2007

Between 2001 and 2005, around £250 million was spent on construction research in UK universities. The funds were either directly allocated to projects or indirectly as core funds to support research infrastructure. The latter were allocated according to the standing and vitality or ‘power’ of the research groups, the average of which in 2001 showed a dramatic but little publicised improvement over 1996. This paper describes the process used to assess that research power and then analyses the data for the last assessment in 2001. It concludes that the UK has around 700 or so civil engineering research academics who are recognised as international in their outlook and whose performance is well above average, despite below-average support. It urges the UK construction professionals to take more advantage of this hidden resource on their doorstep.
Total nitrogen removal from high-strength ammonia recycle stream using a single submerged attached growth bioreactor
Authors: Onnis-Hayden A. , Pedros P.B. , Reade J.
Published: April 2007

An experimental study investigating the nitrogen removal efficiency from the recycle stream generated in the dewatering facility of the anaerobically digested sludge at the Deer Island wastewater treatment plant (WWTP) in Boston was conducted using a single submerged attached growth bioreactor (SAGB), designed for simultaneous nitrification and denitrification. The applied nitrogen loading to the reactor ranged from 0.7 to 2.27 kg-N/m3·d, and the corresponding total nitrogen (TN) removal rate ranged from 0.38 to 1.8 kg-N/m3·d. The observed nitrification rates varied from 0.42 kg-N/m3·d to 1.45 kg-N/m3·d with an ammonia load of 0.5 kg-N/m3·d and 1.8 kg-N/m3·d, respectively. An average nitrification efficiency of 91% was achieved throughout the experiment. Denitrification efficiency varied from 55%, obtained without any addition of carbon source, to 95% when methanol was added in order to obtain a methanol/nitrate ratio of about 3 kg methanol/kg NO3−-N.
Inhibitory effect of the xenobiotic 1,2-dichloroethane in a nitrifying biofilm reactor
Authors: Alpaslan Kocamemi B. , Çeçen F.
Published: April 2007

The aim was to investigate the inhibitory effect of the xenobiotic 1,2-DCA on nitrification during the cometabolic degradation in a packed bed nitrifying biofilm reactor. This xenobiotic inhibited primarily the conversion of NH4-N to hydroxylamine by binding to the AMO enzyme. It had no inhibitory effect on the conversion of nitrite to nitrate. At high NH4-N loadings, the presence of 1,2-DCA inhibited NH4-N utilisation more severely than at low loadings. The suppressing effect of 1,2-DCA on NH4-N utilisation was found to be reversible due to the ability of cells to recover from inhibition. These results could fill a gap in the literature about the potential use of nitrifying biofilm systems for cometabolic treatment of 1,2-DCA and could be useful in the design of engineered 1,2-DCA remediation/treatment in biofilm reactors.
Performances of a granular sequencing batch reactor (GSBR)
Authors: Torregrossa M. , Di Bella G. , Viviani G. , Gnoffo A.
Published: April 2007

Aerobic granulation in sequencing batch reactors is widely reported in literature and in particular in SBAR (Sequencing batch airlift reactor) configuration, due to the high localised hydrodynamic shear forces that occur in this type of configuration. The aim of this work was to observe the phenomenon of the aerobic granulation and to confirm the excellent removal efficiencies that can be achieved with this technology. In order to do that, a laboratory-scale plant, inoculated with activated sludge collected from a conventional WWTP, was operated for 64 days: 42 days as a SBAR and 22 days as a SBBC (sequencing batch bubble column). The performances of the pilot plant showed excellent organics removal. COD and BOD removal efficiencies were respectively, 93 and 94%; on the contrary, N-removal efficiency was extremely low (5%–45%). The granules dimensions increased during the whole experimentation; change of reactor configuration contributed to further improve this aspect. The experimental work confirmed the essential role of hydraulic settling time in the formation of aerobic granules and in the sludge settleability and the need to find an optimum between granule size and oxygen supply to achieve good N-removal efficiency.
A pilot-plant study of a moving-bed biofilm reactor system using PVA gel as a biocarrier for removals of organic carbon and nitrogen
Authors: Rouse J.D. , Burica O. , Stražar M. , Levstek M.
Published: April 2007

A pilot-plant study was conducted to evaluate the performance of a moving-bed biofilm reactor process using PVA-gel beads as a biocarrier. Real primary-settled wastewater was fed to the pre-denitrification system and removals of nitrogenous and organic contaminants were evaluated over a 1-year period. The results demonstrated that at a total nitrogen (TN) loading of 18 mg/L.h, a TN removal efficiency in keeping with and even exceeding the theoretical maximum efficiency based on the level of internal recycle, was possible and a nitrification rate of 15 mg/L.h was sustained with a HRT of only 2.5 h at 15 °C. Furthermore, soluble COD and BOD5 in the effluent of the pilot plant were reduced to levels well below most regulatory discharge limits. In addition, the possibility of using this biocarrier in a system, including the elimination of waste organic sludge, was discussed.
Effect of temperature and salinity on the wastewater treatment performance of aerobic submerged fixed bed biofilm reactors
Authors: Chapanova G. , Jank M. , Schlegel S. , Koeser H.
Published: April 2007

The influence of temperature (5–35 °C) and salinity (up to 20 g/l NaCl) on the wastewater purification process in completely mixed and aerated submerged fixed bed biofilm reactors (SFBBRs) was studied. C- and N-conversion in SFBBRs designed according to the DWA (German Association for Water, Wastewater and Waste) rules for carbon removal was investigated for several months on synthetic wastewater.

The DOC degradation rate was even at, according to the DWA, high DOC/BOD loading rates not much affected by temperatures between 5–35 °C and salt contents up to 20 g/L NaCl. At these high DOC loadings an appreciable ammonium conversion could also be observed. The ammonium conversion proved to be sensitive to temperature and salinity. At 5 °C the ammonium removal rate decreased by a factor of five compared to 25–35 °C. Under many operation conditions investigated more than 50% of the converted ammonium was transformed into gaseous nitrogen. The addition of 20 g/L NaCl caused a strong inhibition of the ammonium removal rate over the whole temperature range investigated.
The membrane fouling simulator: a suitable tool for prediction and characterisation of membrane fouling
Authors: Vrouwenvelder J.S. , Bakker S.M. , Cauchard M. , Le Grand R. , Apacandié M. , Idrissi M. , Lagrave S. , Wessels L.P. , van Paassen J.A.M. , Kruithof J.C. , van Loosdrecht M.C.M.
Published: April 2007

A new tool–the Membrane Fouling Simulator (MFS) – is developed to measure membrane fouling (pressure drop increase) in a small and simple system, representative for spiral wound membranes applied in water treatment. With the MFS, fouling development can be monitored systematically by (i) pressure drop, (ii) in situ and non-destructive (visual) observations using the sight glass and (iii) analysis of coupons sampled from the membrane sheet in the MFS. A comparison study of the MFS with spiral wound membrane elements (test rigs and a full scale installation) showed the same fouling. The MFS provided reproducible data. The small size and low water and chemical use of the MFS facilitate to perform systematic parallel studies. With the MFS, fouling of membranes applied in water treatment can be characterised.
Simulation of nitrification of municipal wastewater in a Moving Bed™ biofilm process: a bottom-up approach based on a 2D-continuum model for growth and detachment
Authors: Alpkvist E. , Bengtsson J. , Overgaard N. Chr. , Christensson M. , Heyden A.
Published: April 2007

This paper presents a complete mathematical model of a Moving Bed™ biofilm process for waste-water treatment, in particular for the nitrification process. The model is based on a bottom up approach adopting a multidimensional model for the biofilm growth and metabolism and a global mass balance model for the whole reactor. The model shows that oxygen is limiting the amount of biomass involved in the nitrification process. Furthermore, it suggests the existence of an optimal amount biomass for an optimal reactor turnover rate. Studies of two specific new suspended carriers show that the model output is dependable on the geometry of the carrier, and to a satisfactory extent agreeable with measurements.
Estimation of kinetic parameters of a model for deammonification in biofilms and evaluation of the model
Authors: Brockmann D. , Rosenwinke K.-H. , Morgenroth E.
Published: April 2007

A systematic approach to estimate and evaluate parameters for deammonification in biofilms from available experimental data was evaluated. Parameter estimation was based on a regional steady state sensitivity analysis to select relevant parameters and design of experiments based on a local identifiability analysis. The calibrated model was evaluated under different experimental conditions. Nine of the 16 kinetic and stoichiometric parameters had a significant influence on model predictions. Of these nine parameters only six kinetic parameters were identifiable from batch experiments regardless of the experimental design. More parameters were not identifiable due to high correlations between growth rates and the corresponding affinity constant for oxygen. Data from a batch experiment at 2 mg/L dissolved oxygen (DO) were used to estimate inactivation rates and affinity constants for oxygen for ammonium oxidisers (AO), nitrite oxidisers (NO) and anaerobic ammonium oxidisers (AN). In addition, it was found that not only kinetic and stoichiometric parameters but also the external mass transfer resistance significantly affected model predictions. The resulting model was able to reproduce batch test and continuous reactor operation where DO concentrations were similar to those in the batch experiment used for parameter estimation. However, the model overestimated deammonification for a batch experiment at a much higher DO concentration (5 mg/L). Thus, parameter values that are identifiable and are estimated for given environmental conditions may not necessarily be valid for significantly different experimental conditions.
Modelling and dynamic simulation of a pilot-scale moving bed bioreactor for the treatment of municipal wastewater: model concepts and the use of respirometry for the estimation of kinetic parameters
Authors: Plattes M. , Fiorelli D. , Gillé S. , Girard C. , Henry E. , Minette F. , O'Nagy O. , Schosseler P.M.
Published: April 2007

A model for the simulation of a moving bed bioreactor (MBBR) used for the treatment of municipal wastewater is proposed. The model includes attachment of particulates to the biofilm and detachment of biofilm into the bulk liquid. The growth kinetics are modelled with the activated sludge model no. 1 (ASM1). Respirometry was used for the estimation of kinetic parameters. The resulting respirograms featured the typical endogenous and exogenous respiration phases and the respirogram shapes were as expected from analogous respirometry with activated sludge. The estimated parameter set was used for modelling and simulation of the pilot-scale MBBR. The main proportion of biomass in the MBBR was found to be attached as biofilm on the carrier elements (4.1–4.6 g dm−3) and only a small amount was suspended in the bulk liquid (0.15 g dm−3). Attachment and detachment rates were estimated to be 4.8–7.5 g m−2 d−1 for attachment and 6.5–7.5 g m−2 d−1 for detachment. The biofilm age was estimated to be 1.8–2.7 d. The model was used to predict effluent quality parameters and a good fit of the simulated data to the measured data originating from a four-days-long measurement campaign was obtained.
Optimizing and modelling nitrogen removal in a new configuration of the moving-bed biofilm reactor process
Authors: Larrea L. , Albizuri J. , Abad A. , Larrea A. , Zalakain G.
Published: April 2007

A new configuration of the moving-bed biofilm reactor process with pre-denitrification and nitrification was investigated in a pilot plant, which is fed with urban raw wastewater, the primary settler is located between the anoxic and the aerobic reactors, and primary sludge is recycled to the anoxic reactor as a hybrid pre-denitrification. The carriers used in the experiments are made of high-density polyethylene, with a diameter of 10 mm and a specific surface area of 400 m2/m3. The new process was compared with conventional pre-denitrification–nitrification using in-series reactors fed with settled wastewater. The new configuration achieved an increase of 45% for the denitrification rate and of 30% for the nitrification rate when compared with conventional configuration. These results were analysed in light of the calibration study of the mixed-culture biofilm (MCB) model and simulations in AQUASIM 2.1 platform. Regarding denitrification, the high values obtained in the new configuration were attributed to a higher removal of the slowly biodegradable substrate (XS) in the anoxic reactor due to the use of raw wastewater and sludge recycle. Accordingly, the amounts of heterotrophic biomass (XH) and XS obtained in simulations were higher in both the biofilm and the bulk liquid. Regarding nitrification, the higher values were attributed to a lower removal of XS in the aerobic reactors and accordingly, a lower accumulation of heterotrophic biomass in the biofilm was found in the simulations.
Determination and localisation of in situ substrate uptake by anaerobic wastewater treatment granular biofilms
Authors: Collins G. , Mahony T. , Enright A.-M. , Gieseke A. , de Beer D. , O'Flaherty V.
Published: April 2007

Radiotracer incubation experiments and beta microimaging, along with fluorescent in situ hybridisation (FISH), are proposed as a complementary approach to specific methanogenic activity testing and measurement of in vitro substrate utilisation rates to understand better the ecophysiology of anaerobic granular biofilms from wastewater treatment reactors.
Using microbial genomics to evaluate the effectiveness of silver to prevent biofilm formation
Authors: Wu M.-Y. , Suryanarayanan K. , van Ooij W.J. , Oerther D.B.
Published: April 2007

Increasingly, monovalent silver cations are being considered as an alternative biocide in water distribution systems. The objective of this study was to understand how bacteria respond when challenged with silver. The approach used included cultivation of Escherichia coli in planktonic and sessile phases, exposing biomass to a solution of silver nitrate and evaluating genetic responses using commercial Affymetrix microarrays. Experimental results showed that lower pH enhanced silver toxicity in a dose-dependent manner. Sessile biomass demonstrated resistance to silver, and the microarray results indicated that the genetic mechanism for silver resistance was similar to the mechanism for copper resistance including upregulation of efflux pumps as well as upregulation of metal oxidoreductases. The gene, copA, a P-type ATPase efflux flux, was upregulated in response to silver exposure, and the gene of CusCFBA, a Cu(I) efflux pump, was also upregulated. The gene of CueO, a robust cuprous oxidase, was also upregulated and may have reduced silver toxicity through oxidation of silver ions. This study is significant because it provides baseline data to understand the genetic response of bacteria to silver biocides.
The effect of detachment on biofilm structure and activity: the oscillating pattern of biofilm accumulation
Authors: Lewandowski Z. , Beyenal H. , Myers J. , Stookey D.
Published: April 2007

In our previous papers we have demonstrated that biofilm structure never reaches a steady state in biofilm reactors; in this paper we link this fact to biofilm detachment and to the oscillating pattern of biofilm accumulation. In one respect reactors supporting suspended microbial growth and reactors supporting attached microbial growth (biofilms) are similar: in both the biomass accumulates in the reactor and is disposed of with the effluent. However, while in reactors with suspended microbial growth biomass accumulation and disposal occur simultaneously, in biofilm reactors these two processes are separated in time. Biomass accumulation in biofilm reactors shows a distinct pattern composed of three phases: (1) growth, (2) detachment, (3) regrowth. Despite this distinct pattern of biofilm accumulation observed at the microscale, biofilm reactors do reach a steady state of substrate removal.