bluuebunny/crossref_metadata_2025 huggingface dataset:
Epilepsy-Related Ligand/Receptor Complex LGI1 and ADAM22 Regulate Synaptic Transmission
Authors: Fukata Yuko , Adesnik Hillel , Iwanaga Tsuyoshi , Bredt David S. , Nicoll Roger A. , Fukata Masaki
Published: September 2006

Abnormally synchronized synaptic transmission in the brain causes epilepsy. Most inherited forms of epilepsy result from mutations in ion channels. However, one form of epilepsy, autosomal dominant partial epilepsy with auditory features (ADPEAF), is characterized by mutations in a secreted neuronal protein, LGI1. We show that ADAM22, a transmembrane protein that when mutated itself causes seizure, serves as a receptor for LGI1. LGI1 enhances AMPA receptor-mediated synaptic transmission in hippocampal slices. The mutated form of LGI1 fails to bind to ADAM22. ADAM22 is anchored to the postsynaptic density by cytoskeletal scaffolds containing stargazin. These studies in rat brain indicate possible avenues for understanding human epilepsy.
Waking Experience Affects Sleep Need in
Drosophila
Authors: Ganguly-Fitzgerald Indrani , Donlea Jeff , Shaw Paul J.
Published: September 2006

Sleep is a vital, evolutionarily conserved phenomenon, whose function is unclear. Although mounting evidence supports a role for sleep in the consolidation of memories, until now, a molecular connection between sleep, plasticity, and memory formation has been difficult to demonstrate. We establish
Drosophila
as a model to investigate this relation and demonstrate that the intensity and/or complexity of prior social experience stably modifies sleep need and architecture. Furthermore, this experience-dependent plasticity in sleep need is subserved by the dopaminergic and adenosine 3′,5′-monophosphate signaling pathways and a particular subset of 17 long-term memory genes.
Risk of injury in elite football played on artificial turf versus natural grass: a prospective two-cohort study
Authors: Ekstrand J , Timpka T , Hägglund M
Published: September 2006

Objective:To compare injury risk in elite football played on artificial turf compared with natural grass.

Design:Prospective two-cohort study.

Setting:Male European elite football leagues.

Participants:290 players from 10 elite European clubs that had installed third-generation artificial turf surfaces in 2003–4, and 202 players from the Swedish Premier League acting as a control group.

Main outcome measure:Injury incidence.

Results:The incidence of injury during training and match play did not differ between surfaces for the teams in the artificial turf cohort: 2.42v2.94 injuries/1000 training hours and 19.60v21.48 injuries/1000 match hours for artificial turf and grass respectively. The risk of ankle sprain was increased in matches on artificial turf compared with grass (4.83v2.66 injuries/1000 match hours; rate ratio 1.81, 95% confidence interval 1.00 to 3.28). No difference in injury severity was seen between surfaces. Compared with the control cohort who played home games on natural grass, teams in the artificial turf cohort had a lower injury incidence during match play (15.26v23.08 injuries/1000 match hours; rate ratio 0.66, 95% confidence interval 0.48 to 0.91).

Conclusions:No evidence of a greater risk of injury was found when football was played on artificial turf compared with natural grass. The higher incidence of ankle sprain on artificial turf warrants further attention, although this result should be interpreted with caution as the number of ankle sprains was low.
Enhanced expression of Giα protein and adenylyl cyclase signaling in aortas from 1 kidney 1 clip hypertensive ratsThis paper is one of a selection of papers published in this Special issue, entitled Second Messengers and Phosphoproteins—12th International Conference.
Authors: Ge Chang , Garcia Raul , Anand-Srivastava Madhu B.
Published: September 2006

We have previously shown the augmented levels of Giα-2 and Giα-3 proteins (isoforms of inhibitory guanine nucleotide regulatory protein (G-protein)), and not of Gsα, in the hearts and aortas of spontaneously and experimentally induced hypertensive rats. The increased expression of Giα and blood pressure was restored toward WKY levels by captopril treatment, suggesting a role for angiotensin (Ang) II in the enhanced expression of Giα protein and blood pressure. This study was undertaken to investigate whether 1 kidney 1 clip (1K-1C) hypertensive rats that exhibit enhanced levels of Ang II also express enhanced levels of Giα proteins. Aortas from 1K-1C hypertensive rats were used. The expression of G-proteins was determined at protein levels with immunoblotting techniques, using specific antibodies for different isoforms of G-proteins. The levels of Giα-2 and Giα-3 proteins were significantly higher in aortas from 1K-1C hypertensive rats than in control rats; Gsα levels were unchanged. The inhibitory effect of low concentrations of guanosine 5′-[γ-thio]triphosphate (GTPγS) on forskolin (FSK)-stimulated adenylyl cyclase (AC) activity was significantly enhanced in aortas from 1K-1C hypertensive rats; the inhibitory effect of C-ANP4–23, which specifically interacts with the atrial natriuretic peptide (ANP)-C receptor, and Ang II on AC was attenuated. GTPγS, isoproterenol, glucagon, NaF, and FSK stimulated the AC activity in aortas from control and hypertensive rats to varying degrees; however, the stimulations were significantly lower in hypertensive rats than in control rats. These data suggest that aortas from 1K-1C hypertensive rats exhibit enhanced expression of Giα proteins and associated functions.
Vanadyl(IV) complexes with saccharides. Bioactivity in osteoblast-like cells in cultureThis paper is one of a selection of papers published in this Special issue, enititled Second Messengers and Phosphoproteins—12th International Conference.
Authors: Barrio Daniel A. , Cattáneo Elizabeth R. , Apezteguía María C. , Etcheverry Susana B.
Published: September 2006

Complexes of vanadyl(IV) with 4 monosaccharides and 5 disaccharides were tested in 2 osteoblast-like cell lines (MC3T3E1 and UMR106). Many complexes caused stimulation of UMR106 proliferation (120% basal) in the range of 2.5 to 25 µmol/L. In the nontransformed osteoblasts, some vanadyl–saccharide complexes stimulated the mitogenesis (115% basal) in the same range of concentration. The glucose and sucrose complexes were the most efficient inhibitory agents (65% and 88% of inhibition vs. basal, respectively) for tumoral cells at 100 µmol/L. The galactose and turanose complexes exerted a similar effect in the nontransformed osteoblasts. On the other hand, all the complexes promoted the phosphorylation of the extracellular regulated kinases (ERKs). All together, these results indicate that the stimulation of ERKs is not the only factor that plays a role in the proliferative effects of vanadium derivatives since some compounds were inhibitory proliferating agents. Cell differentiation was evaluated by alkaline phosphatase specific activity and collagen synthesis in UMR106 cells. All the complexes inhibited alkaline phosphatase activity, with galactose complex as the most effective compound (IC50= 43 µmol/L). The complex with the trehalose TreVO was the most effective agent to stimulate collagen synthesis (142% basal) and glucose consumption (132% basal). A cytosolic tyrosine protein kinase and the kinase-3 of glycogen synthase seem to be involved in the stimulation of glucose consumption by vanadium derivatives. In this series, only TreVO gathered the characteristics of a good insulin mimetic and osteogenic drug. In addition, this complex was a good promoting agent of nontransformed osteoblast proliferation, whereas it inhibited tumoral osteoblasts. GluVO, the complex with glucose, was also more toxic for tumoral than for nontransformed cells. These 2 vanadium derivatives are good potential antitumoral drugs. All the results suggest that the biological effects of vanadium compounds are a complex phenomenon influenced by the complexation, the dose, and the nature of the ligands and the cells.
Activation of insulin-like growth factor type-1 receptor is required for H2O2-induced PKB phosphorylation in vascular smooth muscle cellsThis paper is one of a selection of papers published in this Special issue, entitled Second Messengers and Phosphoproteins—12th International Conference.
Authors: Azar Zeina M. , Mehdi Mohamad Z. , Srivastava Ashok K.
Published: September 2006

Evidence accumulated in recent years has revealed a potential role for reactive oxygen species (ROS) in the pathophysiology of cardiovascular diseases. However, the precise mechanisms by which ROS contribute to the development of these diseases are not fully established. Previous work from our laboratory has indicated that exogenous hydrogen peroxide (H2O2) activates several signaling protein kinases, such as extracellular signal-regulated kinase 1 and 2 (ERK1/2) and protein kinase B (PKB) in A10 vascular smooth muscle cells (VSMC). However, the upstream elements responsible for this activation remain unclear. Although a role for epidermal growth factor receptor (EGFR) protein tyrosine kinase (PTK) in H2O2-induced ERK1/2 signaling has been suggested, the contribution of this PTK or other receptor or nonreceptor PTKs to PKB activation is not well defined in VSMC. In this study, we used pharmacological inhibitors to investigate the role of receptor and Src-family-PTKs in H2O2-induced PKB phosphorylation. AG1478, a specific inhibitor of EGFR, failed to attenuate the H2O2-induced increase in PKB Ser473 phosphorylation, whereas AG1024, an inhibitor of insulin-like growth factor type1 receptor (IGF-1R)-PTK, almost completely blocked this response. H2O2treatment also enhanced tyrosine phosphorylation of the IGF-1Rβ subunit, which was significantly inhibited by AG1024 pretreatment of cells. Furthermore, pharmacological inhibition of Src by PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazole(3,4-d) pyrimidine) decreased PKB phosphorylation. Moreover, H2O2-induced PKB phosphorylation was associated with increased tyrosine phosphorylation of c-Src and Pyk2 in an AG1024- and PP2-inhibitable manner. In conclusion, these data provide evidence of the contribution of IGF-1R-PTK in initiating H2O2-evoked PKB phosphorylation in A10 VSMC, with an intermediary role for c-Src and Pyk2 in this process.
EIGENVALUES AND EIGENFUNCTIONS OF WOODS–SAXON POTENTIAL IN PT-SYMMETRIC QUANTUM MECHANICS
Authors: BERKDEMIR AYŞE , BERKDEMIR CÜNEYT , SEVER RAMAZAN
Published: September 2006

Using the Nikiforov–Uvarov method which is based on solving the second-order differential equations, we firstly analyzed the energy spectra and eigenfunctions of the Woods–Saxon potential. In the framework of the PT-symmetric quantum mechanics, we secondly solved the time-independent Schrödinger equation for the PT and non-PT-symmetric version of the potential. It is shown that the discrete energy eigenvalues of the non-PT-symmetric potential consist of the real and imaginary parts, but the PT-symmetric one has a real spectrum. Results are obtained for s-states only.
EVIDENCE OF TRAP DISTRIBUTION IN BORATE GLASS
Authors: SINGH S. NABADWIP , SHARMA B. ARUNKUMAR , SINGH A. NABACHANDRA
Published: September 2006

In order to elucidate the type of trap distribution in borate glass we have analyzed a set of glow peaks around 110°C recorded with different doses of β-ray irradiation. The glow curves are subjected to the rigorous Computerized Glow Curve Deconvolution (CGCD) both in the framework of kinetic formalism and differential equation formalism to judge which type of trap distribution favors in borate glass. It is observed that the distribution of traps is exponential, which is also well supported by standard error analyses i.e. Figure Of Merit (FOM) and Chi-square (χ2) test.
ELECTRICAL AND OPTICAL PROPERTIES OF MULTILAYER SOL GEL ZnO COATINGS
Authors: HAMMAD TALAAT MOUSSA
Published: September 2006

Multilayer transparent conducting zinc oxide films have been prepared on boro-silicate substrates by the commercially sol gel dip coating process. Each layer was fired at 550°C in a conventional furnace for 15 min. The final coatings were then tempered under a flux of forming gas ( N 2/ H 2) at 400°C for 2 h. The coatings were characterized by surface stylus profiling and optical spectroscopy (UV-NIR). Results show that (1) ZnO films with electrical resistivity of 6×10-4 Ω· cm , free carrier mobility of approximately 77 cm 2/ V · s and free carrier density of approximately 6.14×1019 cm -3 are obtained for multilayers 310 nm and (2) the transmittance is approximately 60.4% and the reflectance is nearly 34.7% are obtained at a wavelength of 800 nm when the thickness of the ZnO multilayers is 310 nm. The crystal structure and grain orientation of ZnO films were determined by X-ray diffraction. SEM investigations revealed that the surface morphology of growing ZnO films on boro-silicate substrate is dominated by the smooth surface with a fine microstructure.
CONTRIBUTIONS OF DOMAIN-RELATED PHENOMENA ON DIELECTRIC CONSTANT OF LEAD-BASED FERROELECTRIC CERAMICS UNDER UNIAXIAL COMPRESSIVE PRE-STRESS
Authors: YIMNIRUN RATTIKORN
Published: September 2006

The dielectric constant of lead-based ferroelectric ceramics in three different systems, i.e. BT-PZT, PMN-PT and PMN-PZT, was measured under uniaxial compressive pre-stress to investigate the contributions of different domain-phenomena. The dielectric constant was observed at room temperature under the compressive pre-stress up to 15 MPa, 22 MPa and 5 MPa for BT-PZT, PMN-PT and PMN-PZT, respectively, using a homebuilt uniaxial compressometer. Dielectric constant of the BT-PZT ceramics increased significantly with increasing applied stress. Larger changes in the dielectric constant with the applied stress were observed in the PZT-rich compositions. However, for PMN-PT and PMN-PZT ceramic systems, changes in the dielectric constant with the stress were found to depend significantly on the ceramic compositions. The experimental results could be explained by both intrinsic and extrinsic domain-related mechanisms involving domain wall motions, as well as the de-aging phenomenon from the application of the compressive pre-stress. Roles of different types of domains, i.e. micro-domains and nano-domains, were also discussed.
Platelet-derived growth factor-BB represses smooth muscle cell marker genes via changes in binding of MKL factors and histone deacetylases to their promoters
Authors: Yoshida Tadashi , Gan Qiong , Shang Yueting , Owens Gary K.
Published: September 2006

A hallmark of smooth muscle cell (SMC) phenotypic switching is suppression of SMC marker gene expression. Although myocardin has been shown to be a key regulator of this process, the role of its related factors, MKL1 and MKL2, in SMC phenotypic switching remains unknown. The present studies were aimed at determining if: 1) MKL factors contribute to the expression of SMC marker genes in cultured SMCs; and 2) platelet-derived growth factor-BB (PDGF-BB)-induced repression of SMC marker genes is mediated by suppression of MKL factors. Results of gain- and loss-of-function experiments showed that MKL factors regulated the expression of single and multiple CArG [CC(AT-rich)6GG]-containing SMC marker genes, such as smooth muscle (SM) α-actin and telokin, but not CArG-independent SMC marker genes such as smoothelin-B. Treatment with PDGF-BB reduced the expression of CArG-containing SMC marker genes, as well as myocardin expression in cultured SMCs, while it had no effect on expression of MKL1 and MKL2. However, of interest, PDGF-BB induced the dissociation of MKL factors from the CArG-containing region of SMC marker genes, as determined by chromatin immunoprecipitation assays. This dissociation was caused by the competition between MKL factors and phosphorylated Elk-1 at early time points, but subsequently by the reduction in acetylated histone H4 levels at these promoter regions mediated by histone deacetylases, HDAC2, HDAC4, and HDAC5. Results provide novel evidence that PDGF-BB-induced repression of SMC marker genes is mediated through combinatorial mechanisms, including downregulation of myocardin expression and inhibition of the association of myocardin/MKL factors with CArG-containing SMC marker gene promoters.
Bidirectional Ca2+ coupling of mitochondria with the endoplasmic reticulum and regulation of multimodal Ca2+ entries in rat brown adipocytes
Authors: Kuba Masako , Higure Yoko , Susaki Hisashi , Hayato Ryotaro , Kuba Kenji
Published: September 2006

How the endoplasmic reticulum (ER) and mitochondria communicate with each other and how they regulate plasmalemmal Ca2+ entry were studied in cultured rat brown adipocytes. Cytoplasmic Ca2+ or Mg2+ and mitochondrial membrane potential were measured by fluorometry. The sustained component of rises in cytoplasmic Ca2+ concentration ([Ca2+]i) produced by thapsigargin was abolished by removing extracellular Ca2+, depressed by depleting extracellular Na+, and enhanced by raising extracellular pH. FCCP, dinitrophenol, and rotenone caused bi- or triphasic rises in [Ca2+]i, in which the first phase was accompanied by mitochondrial depolarization. The FCCP-induced first phase was partially inhibited by oligomycin but not by ruthenium red, cyclosporine A, U-73122, a Ca2+-free EGTA solution, and an Na+-free solution. The FCCP-induced second phase paralleling mitochondrial repolarization was partially blocked by removing extracellular Ca2+ and fully blocked by oligomycin but not by thapsigargin or an Na+-deficient solution, was accompanied by a rise in cytoplasmic Mg2+ concentration, and was summated with a high pH-induced rise in [Ca2+]i, whereas the extracellular Ca2+-independent component was blocked by U-73122 and cyclopiazonic acid. The FCCP-induced third phase was blocked by removing Ca2+ but not by thapsigargin, depressed by decreasing Na+, and enhanced by raising pH. Cyclopiazonic acid-evoked rises in [Ca2+]i in a Ca2+-free solution were depressed after FCCP actions. Thus mitochondrial uncoupling causes Ca2+ release, activating Ca2+ release from the ER and store-operated Ca2+ entry, and directly elicits a novel plasmalemmal Ca2+ entry, whereas Ca2+ release from the ER activates Ca2+ accumulation in, or release from, mitochondria, indicating bidirectional mitochondria-ER couplings in rat brown adipocytes.
5-Hydroxytryptophan activates colonic myenteric neurons and propulsive motor function through 5-HT4receptors in conscious mice
Authors: Wang L. , Martínez V. , Kimura H. , Taché Y.
Published: September 2006

Serotonin [5-hydroxytryptamine (5-HT)] acts as a modulator of colonic motility and secretion. We characterized the action of the 5-HT precursor 5-hydroxytryptophan (5-HTP) on colonic myenteric neurons and propulsive motor activity in conscious mice. Fos immunoreactivity (IR), used as a marker of neuronal activation, was monitored in longitudinal muscle/myenteric plexus whole mount preparations of the distal colon 90 min after an intraperitoneal injection of 5-HTP. Double staining of Fos IR with peripheral choline acetyltransferase (pChAT) IR or NADPH-diaphorase activity was performed. The injection of 5-HTP (0.5, 1, 5, or 10 mg/kg ip) increased fecal pellet output and fluid content in a dose-related manner, with a peak response observed within the first 15 min postinjection. 5-HTP (0.5–10 mg/kg) dose dependently increased Fos expression in myenteric neurons, with a maximal response of 9.9 ± 1.0 cells/ganglion [ P < 0.05 vs. vehicle-treated mice (2.3 ± 0.6 cells/ganglion)]. There was a positive correlation between Fos expression and fecal output. Of Fos-positive ganglionic cells, 40 ± 4% were also pChAT positive and 21 ± 5% were NADPH-diaphorase positive in response to 5-HTP, respectively. 5-HTP-induced defecation and Fos expression were completely prevented by pretreatment with the selective 5-HT4antagonist RS-39604. These results show that 5-HTP injected peripherally increases Fos expression in different populations of cholinergic and nitrergic myenteric neurons in the distal colon and stimulates propulsive colonic motor function through 5-HT4receptors in conscious mice. These findings suggest an important role of activation of colonic myenteric neurons in the 5-HT4receptor-mediated colonic propulsive motor response.
Sex difference in urine concentration across differing ages, sodium intake, and level of kidney disease
Authors: Perucca Julie , Bouby Nadine , Valeix Pierre , Bankir Lise
Published: September 2006

Men are known to be at greater risk of urolithiasis and cardiovascular and renal diseases than women. Previous studies suggest that greater urine concentration is associated with acceleration of progression of chronic kidney disease (CKD), increased urinary albumin excretion, and delayed renal sodium excretion. The present review addresses possible sex-related differences in urine volume and osmolality (Uosm) that could participate in this male risk predominance. Because of the scarcity of information, we reanalyzed 24-h urine data collected previously by different investigators for other purposes. In nine studies concerning healthy subjects (6 studies) or patients with CKD or diabetes mellitus, Uosm(or another index of urine concentration based on the urine/plasma creatinine concentration ratio) was 21–39% higher (i.e., about a 150 mosm/kgH2O difference) in men than in women. Urine volume was not statistically different. Thus, the larger osmolar load of men (related to their higher food intake) is excreted in a more concentrated urine with no difference in urine volume. This sex difference was not influenced by the level of sodium excretion and was still present in CKD patients. Sex differences in thirst threshold, AVP level, and other regulatory mediators may all contribute to the higher male Uosm. Because of the previously demonstrated adverse effects of vasopressin and/or high urine concentrating activity, the greater tendency of men to concentrate urine could participate in their greater susceptibility to urolithiasis and hypertension and to the faster progression towards end-stage renal failure.
Evaluation of two-way protein fluxes across the alveolo-capillary membrane by scintigraphy in rats: effect of lung inflation
Authors: de Prost Nicolas , Dreyfuss Didier , Saumon Georges
Published: September 2006

Pulmonary microvascular and alveolar epithelial permeability were evaluated in vivo by scintigraphic imaging during lung distension. A zone of alveolar flooding was made by instilling a solution containing99mTc-albumin in a bronchus. Alveolar epithelial permeability was estimated from the rate at which this tracer left the lungs. Microvascular permeability was simultaneously estimated measuring the accumulation of111In-transferrin in lungs. Four levels of lung distension (corresponding to 15, 20, 25, and 30 cmH2O end-inspiratory airway pressure) were studied during mechanical ventilation. Computed tomography scans showed that the zone of alveolar flooding underwent the same distension as the contralateral lung during inflation with gas. Increasing lung tissue stretch by ventilation at high airway pressure immediately increased microvascular, but also alveolar epithelial, permeability to proteins. The same end-inspiratory pressure threshold (between 20 and 25 cmH2O) was observed for epithelial and endothelial permeability changes, which corresponded to a tidal volume between 13.7 ± 4.69 and 22.2 ± 2.12 ml/kg body wt. Whereas protein flux from plasma to alveolar space (111In-transferrin lung-to-heart ratio slope) was constant over 120 min, the rate at which99mTc-albumin left air spaces decreased with time. This pattern can be explained by changes in alveolar permeability with time or by a compartment model including an intermediate interstitial space.
Effects of intermittent hypoxic training on amino and fatty acid oxidative combustion in human permeabilized muscle fibers
Authors: Roels Belle , Thomas Claire , Bentley David J. , Mercier Jacques , Hayot Maurice , Millet Grégoire
Published: September 2006

The effects of concurrent hypoxic/endurance training on mitochondrial respiration in permeabilized fibers in trained athletes were investigated. Eighteen endurance athletes were divided into two training groups: normoxic (Nor, n = 8) and hypoxic (H, n = 10). Three weeks (W1–W3) of endurance training (5 sessions of 1 h to 1 h and 30 min per week) were completed. All training sessions were performed under normoxic [160 Torr inspired Po2 (Pi[Formula: see text])] or hypoxic conditions (≈100 Torr Pi[Formula: see text], ≈3,000 m) for Nor and H group, respectively, at the same relative intensity. Before and after the training period, an incremental test to exhaustion in normoxia was performed, muscle biopsy samples were taken from the vastus lateralis, and mitochondrial respiration in permeabilized fibers was measured. Peak power output (PPO) increased by 7.2% and 6.6% ( P < 0.05) for Nor and H, respectively, whereas maximal O2 uptake (V̇o2 max) remained unchanged: 58.1 ± 0.8 vs. 61.0 ± 1.2 ml·kg−1·min−1 and 58.5 ± 0.7 vs. 58.3 ± 0.6 ml·kg−1·min−1 for Nor and H, respectively, between pretraining (W0) and posttraining (W4). Maximal ADP-stimulated mitochondrial respiration significantly increased for glutamate + malate (6.27 ± 0.37 vs. 8.51 ± 0.33 μmol O2·min−1·g dry weight−1) and significantly decreased for palmitate + malate (3.88 ± 0.23 vs. 2.77 ± 0.08 μmol O2·min−1·g dry weight−1) in the H group. In contrast, no significant differences were found for the Nor group. The findings demonstrate that 1) a 3-wk training period increased the PPO at sea level without any changes in V̇o2 max, and 2) a 3-wk hypoxic exercise training seems to alter the intrinsic properties of mitochondrial function, i.e., substrate preference.
The Emerging Structure of Vacuolar ATPases
Authors: Drory Omri , Nelson Nathan
Published: September 2006

Bioenergetics and physiology of primary pumps have been revitalized by new insights into the mechanism of energizing biomembranes. Structural information is becoming available, and the three-dimensional structure of F-ATPase is being resolved. The growing understanding of the fundamental mechanism of energy coupling may revolutionize our view of biological processes. The F- and V-ATPases (vacuolar-type ATPase) exhibit a common mechanical design in which nucleotide-binding on the catalytic sector, through a cycle of conformation changes, drives the transmembrane passage of protons by turning a membrane-embedded rotor. This motor can run in forward or reverse directions, hydrolyzing ATP as it pumps protons uphill or creating ATP as protons flow downhill. In contrast to F-ATPases, whose primary function in eukaryotic cells is to form ATP at the expense of the proton-motive force (pmf), V-ATPases function exclusively as an ATP-dependent proton pump. The pmf generated by V-ATPases in organelles and membranes of eukaryotic cells is utilized as a driving force for numerous secondary transport processes. V- and F-ATPases have similar structure and mechanism of action, and several of their subunits evolved from common ancestors. Electron microscopy studies of V-ATPase revealed its general structure at low resolution. Recently, several structures of V-ATPase subunits, solved by X-ray crystallography with atomic resolution, were published. This, together with electron microscopy low-resolution maps of the whole complex, and biochemistry cross-linking experiments, allows construction of a structural model for a part of the complex that may be used as a working hypothesis for future research.
The mTOR Pathway in the Control of Protein Synthesis
Authors: Wang Xuemin , Proud Christopher G.
Published: September 2006

Signaling through mammalian target of rapamycin (mTOR) is activated by amino acids, insulin, and growth factors, and impaired by nutrient or energy deficiency. mTOR plays key roles in cell physiology. mTOR regulates numerous components involved in protein synthesis, including initiation and elongation factors, and the biogenesis of ribosomes themselves.
Complete Resolution of Acute Renal Failure after Left Renal Artery Angioplasty and Stent Placement for Total Renal Artery Occlusion
Authors: Rehan Arshad , Almanaseer Yassar , Desai Devang M. , Ali Arshad , Yamasaki Hiroshi
Published: September 2006

A 25-year-old female, 17 weeks pregnant presented to our hospital with complaints of progressively increasing dyspnea. She was hypertensive with creatine of 1.0; she was transferred to ICU with multiple medications to control her blood pressure, without success. The patient continued to decompensate, which required intubation. The patient developed acute renal failure, part of her work-up suggested bilateral renal artery stenosis. She was taken to the catheterization lab and was found to have bilateral total renal artery occlusion. The left renal artery was successfully opened. The patient recovered and her blood pressure was controlled after the procedure. In the past, surgery was the preferred treatment in cases of acute renal artery occlusion. This approach has been replaced increasingly by renal artery angioplasty, which is less invasive and is at least as effective as surgical reconstruction. Our case demonstrates a percutaneous approach can be tried for totally occluded renal artery with a successful outcome.
Renal Tubular Dysgenesis: Report of Two Cases in a Non-Consanguineous Couple and Review of the Literature
Authors: Ramalho C. , Matias A. , Brandão O. , Montenegro N.
Published: September 2006

Renal tubular dysgenesis is a rare congenital abnormality of renal development characterized by short and poorly developed proximal convoluted tubules. It is associated to late-appearing oligohydramnios, Potter’s sequence, pulmonary hypoplasia and calvarial bone hypoplasia with enlarged fontanels. The onset of oligohydramnios is delayed and variable, normally later than 22 weeks of gestation, conditioning variation in the expression of the other deformities. We report 2 cases of renal tubular dysgenesis occurring in a non-consanguineous couple.
Does the Source of Laser Energy Influence the Coagulation of Chorionic Plate Vessels? Comparison of Nd:YAG and Diode Laser on an ex vivo Placental Model
Authors: Nizard Jacky , Barbet Jacques Patrick , Ville Yves
Published: September 2006

Objectives: To compare the histological effects of diode and Neodymium-Yttrium Aluminium Garnet (Nd:YAG) laser coagulation of chorionic plate vessels. Methods: In selected chorionic plate vessels in an ex vivo term placenta perfused with warm saline solution, diode (wavelength 940 nm) and Nd:YAG (wave length 1,064 nm) laser were used with an output of 30, 40, and 50 W, and 55 and 70 W respectively using preset energy and duration of impact. All vessels were examined histologically blindly to the procedures’ characteristics. Results: A total of 23 vessels were coagulated. Similar histological lesions were observed using diode and Nd:YAG lasers. The lesions were compatible with an acceptable clinical effect at all power outputs tested. The results were not related to the diameter or type of vessels. Lesions of the endothelium and reduction of the vessel lumen were best achieved with a diode laser at 40 W. Conclusion: Nd:YAG and Diode laser induce significant and comparable changes in chorionic plate vessels compatible with an efficient coagulation process under the experimental condition used.
Amniotic Band Syndrome with Limb Amputation after Exposure to Mifepristone in Early Pregnancy
Authors: Sentilhes Loïc , Patrier Sophie , Chouchene Sadok , Diguet Alain , Berthier Aurélien , Marpeau Loïc , Verspyck Eric
Published: September 2006

To date, the number of cases reported after exposure to mifepristone alone in early pregnancy is limited. In 24 cases, only 1 observation of fetal malformation associated with mifepristone has previously been reported. We report a case of amniotic band syndrome with limb amputation after exposure to mifepristone in early pregnancy. This association raises the question of a possible causal relationship.
Parvovirus B19 Infection in Pregnancy Studied by Maternal Viral Load and Immune Responses
Authors: de Haan Timo R. , Beersma Matthias F.C. , Claas Eric C.J. , Oepkes Dick , Kroes Aloys C.M. , Walther Frans J.
Published: September 2006

Objectives: Facilitate risk assessment of vital complications in fetuses of pregnancies affected by acute parvovirus B19 (B19V) infection. Design: Study of the natural course of maternal B19V infection in four cases, from early pregnancy on. Setting: University Medical Center in the Netherlands. Population: Pregnant mothers attending obstetric services. Methods: Serial measurements of the maternal and fetal or neonatal viral load and antibody responses. Main Outcome Measures: Maternal and fetal/neonatal serum B19V viral DNA load and specific IgM and IgG antibodies in maternal serum. Results: Peak viral load levels occurred within 1 week after maternal infection and peak IgM levels were observed 1 week after the peak viral load levels. Approximation of IgG and IgM ratios usually took place 4 weeks after infection. Vertical transmission occurred 1–3 weeks after maternal infection, suggesting that fetal infection occurs during the maternal peak viral load. Conclusions: Maternal B19V DNA load levels and IgM responses are useful to estimate the risk of parvovirus B19-associated fetal complications. The maternal peak viral load directly precedes the onset of fetal infection and may be used to indicate the stage of intrauterine B19V infection.
Prostaglandin E2 Induction of Labor for Isolated Oligohydramnios in Women with Unfavorable Cervix at Term
Authors: Danon D. , Ben-Haroush A. , Yogev Y. , Bar J. , Hod M. , Pardo J.
Published: September 2006

Objective: To evaluate the maternal and neonatal outcomes of pregnancies complicated with isolated oligohydramnios at term, managed by induction of labor. Methods: We conducted a retrospective case-control study. 138 women with uncomplicated oligohydramnios at term [amniotic fluid index (AFI) ≤5 cm] and a low Bishop score (≤6) underwent induction of labor with prostaglandin E2. These women were compared to 67 women who underwent induction of labor at 42 weeks’ gestation and 276 women at low-risk pregnancy and spontaneous onset of labor, matched for parity and race. Results: Cesarean section (CS) rate was similar in the study and the post-date group (17.4 and 17.9%, respectively), but significantly higher than the spontaneous labor group (5.8%, OR 3.42, 95% CI 1.75–6.68). No differences were found with other outcomes. Conclusion: Pregnancies with isolated oligohydramnios at term apparently are not at higher risk of perinatal complications, but induction of labor is associated with increased rate of CS.
SNP-Based Analysis of Genetic Substructure in the German Population
Authors: Steffens Michael , Lamina Claudia , Illig Thomas , Bettecken Thomas , Vogler Rainer , Entz Patricia , Suk Eun-Kyung , Toliat Mohammad Reza , Klopp Norman , Caliebe Amke , König Inke R. , Köhler Karola , Lüdemann Jan , Diaz Lacava Amalia , Fimmers Rolf , Lichtner Peter , Ziegler Andreas , Wolf Andreas , Krawczak Michael , Nürnberg Peter , Hampe Jochen , Schreiber Stefan , Meitinger Thomas , Wichmann H.-Erich , Roeder Kathryn , Wienker Thomas F. , Baur Max P.
Published: September 2006

Objective: To evaluate the relevance and necessity to account for the effects of population substructure on association studies under a case-control design in central Europe, we analysed three samples drawn from different geographic areas of Germany. Two of the three samples, POPGEN (n = 720) and SHIP (n = 709), are from north and north-east Germany, respectively, and one sample, KORA (n = 730), is from southern Germany. Methods: Population genetic differentiation was measured by classical F-statistics for different marker sets, either consisting of genome-wide selected coding SNPs located in functional genes, or consisting of selectively neutral SNPs from ‘genomic deserts’. Quantitative estimates of the degree of stratification were performed comparing the genomic control approach [Devlin B, Roeder K: Biometrics 1999;55:997–1004], structured association [Pritchard JK, Stephens M, Donnelly P: Genetics 2000;155:945–959] and sophisticated methods like random forests [Breiman L: Machine Learning 2001;45:5–32]. Results: F-statistics showed that there exists a low genetic differentiation between the samples along a north-south gradient within Germany (FST(KORA/POPGEN): 1.7 · 10–4; FST(KORA/SHIP): 5.4 · 10–4; FST(POPGEN/SHIP): –1.3 · 10–5). Conclusion: Although the FST -values are very small, indicating a minor degree of population structure, and are too low to be detectable from methods without using prior information of subpopulation membership, such as STRUCTURE [Pritchard JK, Stephens M, Donnelly P: Genetics 2000;155:945–959], they may be a possible source for confounding due to population stratification.
Human Population Genetic Structure and Diversity Inferred from Polymorphic L1(LINE-1) and Alu Insertions
Authors: Witherspoon D.J. , Marchani E.E. , Watkins W.S. , Ostler C.T. , Wooding S.P. , Anders B.A. , Fowlkes J.D. , Boissinot S. , Furano A.V. , Ray D.A. , Rogers A.R. , Batzer M.A. , Jorde L.B.
Published: September 2006

Background/Aims: The L1 retrotransposable element family is the most successful self-replicating genomic parasite of the human genome. L1 elements drive replication of Alu elements, and both have had far-reaching impacts on the human genome. We use L1 and Alu insertion polymorphisms to analyze human population structure. Methods: We genotyped 75 recent, polymorphic L1 insertions in 317 individuals from 21 populations in sub-Saharan Africa, East Asia, Europe and the Indian subcontinent. This is the first sample of L1 loci large enough to support detailed population genetic inference. We analyzed these data in parallel with a set of 100 polymorphic Alu insertion loci previously genotyped in the same individuals. Results and Conclusion: The data sets yield congruent results that support the recent African origin model of human ancestry. A genetic clustering algorithm detects clusters of individuals corresponding to continental regions. The number of loci sampled is critical: with fewer than 50 typical loci, structure cannot be reliably discerned in these populations. The inclusion of geographically intermediate populations (from India) reduces the distinctness of clustering. Our results indicate that human genetic variation is neither perfectly correlated with geographic distance (purely clinal) nor independent of distance (purely clustered), but a combination of both: stepped clinal.
Regulation of ROMK (Kir 1.1) Channel Expression in Kidney Thick Ascending Limb by Hypertonicity: Role of TonEBP and MAPK Pathways
Authors: Gallazzini Morgan , Karim Zoubida , Bichara Maurice
Published: September 2006

The present study assessed the mechanisms by which hypertonicity caused by NaCl enhances the renal outer medullary potassium channel (ROMK) mRNA abundance in rat kidney medullary thick ascending limb (MTAL) and in cultured mouse TAL cells. Using the run-off technique, we observed that the ROMK gene transcription rate in nuclei isolated from MTAL fragments was enhanced ∼40% by a high NaCl medium. In MTAL fragments, hypertonicity (450 mosm) caused by NaCl, not by mannitol or urea, enhanced both ROMK mRNA abundance and tonicity-responsive enhancer binding protein (TonEBP) total abundance and nuclear localization. In an immortalized mouse TAL cell culture in which ROMK is apically expressed, hypertonicity caused by both NaCl and mannitol, not urea, enhanced both ROMK mRNA abundance and TonEBP total abundance and nuclear localization. Confocal microscopy confirmed an increased nuclear translocation of TonEBP in response to NaCl-induced hypertonicity. Finally, inhibition of the p38 MAPK pathway by SB203580 and of the ERK pathway by PD98059 abolished the NaCl-induced stimulation of TonEBP and ROMK. These results establish that mRNA expression of ROMK is augmented in the MTAL by NaCl-induced hypertonicity through stimulation of ROMK gene transcription, and that TonEBP and the p38 MAPK and ERK pathways are involved in this effect.
Angiotensin II Regulates Extraneuronal Dopamine Uptake in the Kidney
Authors: Choi Marcelo R. , Correa Alicia H. , del Valle Turco Vanesa , Garcia Fernando Aprile , Fernández Belisario E.
Published: September 2006

Background/Aims: Angiotensin II (ANG II) and dopamine (DA) are both important regulators of sodium and water transport across renal proximal tubules. Previous studies demonstrate that atrial natriuretic factor (ANF) can regulate renal DA uptake and thereby Na+,K+-ATPase activity in the external renal cortex. As ANG II counteracts most of the ANF biological effects, the aim of the present study was to evaluate ANG II effects on renal DA metabolism and identify the receptor involved. Methods: To determine ANG II effects on renal DA metabolism, we evaluated 3H-DA uptake in vitro in kidney tissue samples from Sprague-Dawley rats. Results: The results indicate that ANG II decreased DA uptake at 30 min, in a concentration-response fashion, in the external and juxtamedullar cortex. DA uptake was characterized as an extraneuronal uptake and decreased at 0°C and in sodium-free medium. The biological receptor type involved was AT1, since losartan reversed ANG II effects on DA uptake while AT2 receptors were not involved since PD 123319 did not affect ANG II effects. The absence of sodium did not alter the ANG II response. Conclusion: ANG II inhibits DA uptake by kidney tubular cells. These effects implicate AT1 receptors without participation of AT2 receptors. This mechanism could be related to the DA effects on sodium reabsorption and linked to ANG II antinatriuretic effects in the kidney.
Association Analysis of Peroxisome Proliferator-Activated Receptor Gamma Polymorphisms and Late Onset Alzheimer’s Disease in the Finnish Population
Authors: Koivisto Anne M. , Helisalmi Seppo , Pihlajamäki Jussi , Hiltunen Mikko , Koivisto Keijo , Moilanen Leena , Kuusisto Johanna , Helkala Eeva-Liisa , Hänninen Tuomo , Kervinen Kari , Kesäniemi Y. Antero , Laakso Markku , Soininen Hilkka
Published: September 2006

Alzheimer’s disease (AD), especially late-onset AD (LOAD), is a complex disease. To date, the only established genetic risk factor for LOAD is apolipoprotein E (APOE) Ε4, which explains partially the risk of the disease and modifies the age of onset. Peroxisome proliferator-activated receptor γ (PPARγ) regulates the transcription of BACE1 as well as inflammatory responses in the brain and atherosclerotic risk factors known to be involved also in AD. Based on these findings, the gene encoding PPARγ can be viewed as an interesting candidate in AD. We examined the effect of the two previously reported variants of PPARγ polymorphisms, the Pro12Ala and exon 6 C478T, on the risk of LOAD and age of onset in a population-based follow-up sample of aged subjects (125 LOAD patients and 462 non-demented controls). The genetic risk of AD was not significantly associated with the studied polymorphisms, but the PPARγ Ala12-478T genotype carriers were significantly younger at the onset of dementia than the non-carriers (p = 0.026). These results suggest that the PPARγ gene may modify the age of onset in LOAD.
Additive Effect of Dextromethorphan on the Inhibitory Effect of Anti-NT4 on Morphine Tolerance
Authors: Hatami Homeira , Oryan Shahrbanoo , Semnanian Saeed , Kazemi Bahram , Ahmadiani Abolhassan
Published: September 2006

It has been proposed that opioid tolerance is a model of neuronal plasticity similar to learning and memory. Recent evidence suggests that neurotrophins may be involved in synaptic development and plasticity. Observations indicate that neurotrophin 4 (NT4) is required for the synaptic plasticity mediating both tolerance and memory. Also there are lines of evidence to indicate that NMDA receptors are involved in the neural plasticity underlying the development of opiate tolerance. Neurotrophins affect central transmission postsynaptically by enhancing NMDA receptor responsiveness. So we used the clinically available NMDA receptor antagonist, dextromethorphan, and the neurotrophin 4 antibody, anti-NT4, concomitantly and alone to investigate their effects on morphine tolerance. Tolerance was induced by injecting morphine (7 and 10 mg/kg i.p.) once per day for 4 days. Anti-NT4 (1 µg/rat i.c.v.) was administered 15 min before morphine. Results showed that chronic concomitant treatment of anti-NT4 with morphine in both doses inhibited the development of morphine tolerance. Also acute treatment of anti-NT4 significantly reversed the tolerance that was induced by morphine 7 mg/kg but failed to reverse the tolerance of morphine 10 mg/kg. Dextromethorphan in both doses (10 or 30 mg/kg) has an additive effect on the inhibitory effect of anti-NT4 on the reversal of morphine tolerance (7 mg/kg). These findings provide additional support for the hypothesis that NMDA receptor and NT4 may be involved in neural plasticity underlying opiate tolerance.
Contralateral Suppression of Transient Evoked Otoacoustic Emissions in Children with Auditory Processing Disorder
Authors: Sanches S.G.G. , Carvallo R.M.
Published: September 2006

This study concerns contralateral white noise suppression of transient evoked otoacoustic emissions (TEOAEs) in children with auditory processing disorder (APD). Fifty-one children between 7 and 11 years were assigned to 1 of 3 experimental groups: those without auditory complaints (n = 15), those with APD who scored high on a standardized test (n = 20) and those with APD who scored lower on the same test (n = 16). For all groups TEOAE suppression was determined in both linear and nonlinear acquisition mode. The results provide evidence that abnormal TEOAE suppression was significantly more common in the APD groups than in the control group. Contralateral suppression of TEOAE is an additional tool for assessing the efferent pathway in children with APD.
Antonín Vančura and Arterial Hypertension
Authors: Horký Karel
Published: September 2006

A historical overview of the important contributions of Prof. Antonin Vančura from Charles University Medical Faculty, Prague, to the broader understanding of the pathogenesis, clinical course and classification of arterial hypertension is given in his pivotal publication and first Czech monography ‘High Blood Pressure’. His unique clinical series of 1,096 hypertensive patients with their long-term follow-up after 5, 10 and 15 years made it possible to work out the classification of hypertension not only on the basis of blood pressure readings, but also according to target organ damage – a principle which is close to the 2003 classification of the European Society of Hypertension/European Society of Cardiology (ESH/ESC). In agreement with today’s conception, Vančura emphasized already in 1942 the importance of metabolic changes and albuminuria for prognosis of the disease. In spite of the technical, instrumental and laboratory limitations, it is possible to gain from Vančura’s publication a modern interpretation of his results given by a long-term follow-up of this large group of patients. In many ways, Vančura outstripped his time and his concepts approached today’s standings and so founded one of the important schools of hypertension in Czechoslovakia and Europe.