bluuebunny/crossref_metadata_2025 huggingface dataset:
Binding-Site Identification and Genotypic Profiling of Hepatitis C Virus Polymerase Inhibitors
Authors: Pauwels Frederik , Mostmans Wendy , Quirynen Ludo M. M. , van der Helm Liesbet , Boutton Carlo W. , Rueff Anne-Stéphanie , Cleiren Erna , Raboisson Pierre , Surleraux Dominique , Nyanguile Origène , Simmen Kenneth A.
Published: April 2007

The search for hepatitis C virus polymerase inhibitors has resulted in the identification of several nonnucleoside binding pockets. The shape and nature of these binding sites differ across and even within diverse hepatitis C virus genotypes. These differences confront antiviral drug discovery with the challenge of finding compounds that are capable of inhibition in variable binding pockets. To address this, we have established a hepatitis C virus mutant and genotypic recombinant polymerase panel as a means of guiding medicinal chemistry through the elucidation of the site of action of novel inhibitors and profiling against genotypes. Using a genotype 1b backbone, we demonstrate that the recombinant P495L, M423T, M414T, and S282T mutant enzymes can be used to identify the binding site of an acyl pyrrolidine analog. We assess the inhibitory activity of this analog and other nonnucleoside inhibitors with our panel of enzyme isolates generated from clinical sera representing genotypes 1a, 1b, 2a, 2b, 3a, 4a, 5a, and 6a.
Enhanced Antiviral Activity against Foot-and-Mouth Disease Virus by a Combination of Type I and II Porcine Interferons
Authors: Moraes Mauro Pires , de los Santos Teresa , Koster Marla , Turecek Traci , Wang He , Andreyev Vladimir G. , Grubman Marvin J.
Published: April 2007

Previously, we showed that type I interferon (alpha/beta interferon [IFN-α/β]) can inhibit foot-and-mouth disease virus (FMDV) replication in cell culture, and swine inoculated with 109PFU of human adenovirus type 5 expressing porcine IFN-α (Ad5-pIFN-α) were protected when challenged 1 day later. In this study, we found that type II pIFN (pIFN-γ) also has antiviral activity against FMDV in cell culture and that, in combination with pIFN-α, it has a synergistic antiviral effect. We also observed that while each IFN alone induced a number of IFN-stimulated genes (ISGs), the combination resulted in a synergistic induction of some ISGs. To extend these studies to susceptible animals, we inoculated groups of swine with a control Ad5, 108PFU of Ad5-pIFN-α, low- or high-dose Ad5-pIFN-γ, or a combination of Ad5-pIFN-α and low- or high-dose Ad5-pIFN-γ and challenged all groups with FMDV 1 day later. The control group and the groups inoculated with either Ad5-pIFN-α or a low dose of Ad5-pIFN-γ developed clinical disease and viremia. However, the group that received the combination of both Ad5-IFNs with the low dose of Ad5-pIFN-γ was completely protected from challenge and had no viremia. Similarly the groups inoculated with the combination of Ad5s with the higher dose of Ad5-pIFN-γ or with only high-dose Ad5-pIFN-γ were protected. The protected animals did not develop antibodies against viral nonstructural (NS) proteins, while all infected animals were NS protein seropositive. No antiviral activity or significant levels of IFNs were detected in the protected groups, but there was an induction of some ISGs. The results indicate that the combination of type I and II IFNs act synergistically to inhibit FMDV replication in vitro and in vivo.
Highly Conserved Configuration of Catalytic Amino Acid Residues among Calicivirus-Encoded Proteases
Authors: Oka Tomoichiro , Yamamoto Mami , Yokoyama Masaru , Ogawa Satoko , Hansman Grant S. , Katayama Kazuhiko , Miyashita Kana , Takagi Hirotaka , Tohya Yukinobu , Sato Hironori , Takeda Naokazu
Published: April 2007

A common feature of caliciviruses is the proteolytic processing of the viral polyprotein catalyzed by the viral 3C-like protease encoded in open reading frame 1 (ORF1). Here we report the identification and structural characterization of the protease domains and amino acid residues in sapovirus (SaV) and feline calicivirus (FCV). The in vitro expression and processing of a panel of truncated ORF1 polyproteins and corresponding mutant forms showed that the functional protease domain is 146 amino acids (aa) in SaV and 154 aa in FCV. Site-directed mutagenesis of the protease domains identified four amino acid residues essential to protease activities: H
31
, E
52
, C
116
, and H
131
in SaV and H
39
, E
60
, C
122
, and H
137
in FCV. A computer-assisted structural analysis showed that despite high levels of diversity in the primary structures of the protease domains in the family
Caliciviridae
, the configurations of the H, E, C, and H residues are highly conserved, with these residues positioned closely along the inner surface of the potential binding cleft for the substrate. These results strongly suggest that the H, E, C, and H residues are involved in the formation of a conserved catalytic surface of the SaV and FCV 3C-like proteases.
A HYBRID FEATURE SELECTION METHOD FOR TEXT CATEGORIZATION
Authors: MONTAÑÉS E. , QUEVEDO J. R. , COMBARRO E. F. , DÍAZ I. , RANILLA J.
Published: April 2007

Feature Selection is an important task within Text Categorization, where irrelevant or noisy features are usually present, causing a lost in the performance of the classifiers. Feature Selection in Text Categorization has usually been performed using a filtering approach based on selecting the features with highest score according to certain measures. Measures of this kind come from the Information Retrieval, Information Theory and Machine Learning fields. However, wrapper approaches are known to perform better in Feature Selection than filtering approaches, although they are time-consuming and sometimes infeasible, especially in text domains. However a wrapper that explores a reduced number of feature subsets and that uses a fast method as evaluation function could overcome these difficulties. The wrapper presented in this paper satisfies these properties. Since exploring a reduced number of subsets could result in less promising subsets, a hybrid approach, that combines the wrapper method and some scoring measures, allows to explore more promising feature subsets. A comparison among some scoring measures, the wrapper method and the hybrid approach is performed. The results reveal that the hybrid approach outperforms both the wrapper approach and the scoring measures, particularly for corpora whose features are less scattered over the categories.
FUZZY LINMAP METHOD FOR MULTIATTRIBUTE GROUP DECISION MAKING WITH LINGUISTIC VARIABLES AND INCOMPLETE INFORMATION
Authors: LI DENG-FENG , SUN TAO
Published: April 2007

The aim of this paper is to develop a fuzzy linear programming technique for multidimensional analysis of preference (FLINMAP) in multiattribute group decision making problems with linguistic variables and incomplete preference information. In this paper, linguistic variables are used to assess an alternative on qualitative attributes using fuzzy ratings corresponding to some triangular fuzzy numbers. Each alternative is assessed on the basis of its distance to a fuzzy positive ideal solution (FPIS) which is unknown a priori. The FPIS and the weights of attributes are calculated by constructing a new linear programming model based on the group consistency and inconsistency indices defined on the basis of preferences between alternatives given by the decision makers. The distance of each alternative to the FPIS can be calculated to determine the ranking order of all alternatives. The implementation process of this methodology is demonstrated with an example.
A FUZZY LINGUISTIC IRS MODEL BASED ON A 2-TUPLE FUZZY LINGUISTIC APPROACH
Authors: HERRERA-VIEDMA E. , LÓPEZ-HERRERA A. G. , LUQUE M. , PORCEL C.
Published: April 2007

Information Retrieval Systems (IRSs) based on an ordinal fuzzy linguistic approach present some problems of loss of information and lack of precision when working with discrete linguistic expression domains or when applying approximation operations in the symbolic aggregation methods. In this paper, we present a new IRS model based on the 2-tuple fuzzy linguistic approach, which allows us to overcome the problems of ordinal fuzzy linguistic IRSs and improve their performance.
INTERVAL METHODS IN KNOWLEDGE REPRESENTATION
Authors: Kreinovich Vladik
Published: April 2007

This section is maintained by Vladik Kreinovich. Please send your abstracts (or copies of papers that you want to see reviewed here) to vladik@utep.edu, or by regular mail to: V. Kreinovich, Department of Computer Science, University of Texas, El Paso, TX 79968, USA.
Small- and intermediate-conductance Ca2+-activated K+channels directly control agonist-evoked nitric oxide synthesis in human vascular endothelial cells
Authors: Sheng Jian-Zhong , Braun Andrew P.
Published: April 2007

The contribution of small-conductance (SKCa) and intermediate-conductance Ca2+-activated K+(IKCa) channels to the generation of nitric oxide (NO) by Ca2+-mobilizing stimuli was investigated in human umbilical vein endothelial cells (HUVECs) by combining single-cell microfluorimetry with perforated patch-clamp recordings to monitor agonist-evoked NO synthesis, cytosolic Ca2+transients, and membrane hyperpolarization in real time. ATP or histamine evoked reproducible elevations in NO synthesis and cytosolic Ca2+, as judged by 4-amino-5-methylamino-2′,7′-difluorofluorescein (DAF-FM) and fluo-3 fluorescence, respectively, that were tightly associated with membrane hyperpolarizations. Whereas evoked NO synthesis was unaffected by either tetraethylammonium (10 mmol/l) or BaCl2(50 μmol/l) + ouabain (100 μmol/l), depleting intracellular Ca2+stores by thapsigargin or removing external Ca2+inhibited NO production, as did exposure to high (80 mmol/l) external KCl. Importantly, apamin and charybdotoxin (ChTx)/ triarylmethane (TRAM)-34, selective blockers SKCaand IKCachannels, respectively, abolished both stimulated NO synthesis and membrane hyperpolarization and decreased evoked Ca2+transients. Apamin and TRAM-34 also inhibited an agonist-induced outwardly rectifying current characteristic of SKCaand IKCachannels. Under voltage-clamp control, we further observed that the magnitude of agonist-induced NO production varied directly with the degree of membrane hyperpolarization. Mechanistically, our data indicate that SKCaand IKCachannel-mediated hyperpolarization represents a critical early event in agonist-evoked NO production by regulating the influx of Ca2+responsible for endothelial NO synthase activation. Moreover, it appears that the primary role of agonist-induced release of intracellular Ca2+stores is to trigger the opening of both KCachannels along with Ca2+entry channels at the plasma membrane. Finally, the observed inhibition of stimulated NO synthesis by apamin and ChTx/TRAM-34 demonstrates that SKCaand IKCachannels are essential for NO-mediated vasorelaxation.
O2•− production at 37°C plays a critical role in depressing tetanic force of isolated rat and mouse skeletal muscle
Authors: Edwards Joshua N. , Macdonald William A. , van der Poel Chris , Stephenson D. George
Published: April 2007

To find out whether the decrease in muscle performance of isolated mammalian skeletal muscle associated with the increase in temperature toward physiological levels is related to the increase in muscle superoxide (O2•−) production, O2•− released extracellularly by intact isolated rat and mouse extensor digitorum longus (EDL) muscles was measured at 22, 32, and 37°C in Krebs-Ringer solution, and tetanic force was measured in both preparations at 22 and 37°C under the same conditions. The rate of O2•− production increased marginally when the temperature was increased from 22 to 32°C, but increased fivefold when the temperature was increased from 22 to 37°C in both rat and mouse preparations. This increase was accompanied by a marked decrease in tetanic force after 30 min incubation at 37°C in both rat and mouse EDL muscles. Tetanic force remained largely depressed after return to 22°C for up to 120 min. The specific maximum Ca2+-activated force measured in mechanically skinned fibers after the temperature treatment was markedly depressed in mouse fibers but was not significantly depressed in rat muscle fibers. The resting membrane and intracellular action potentials were, however, significantly affected by the temperature treatment in the rat fibers. The effects of the temperature treatment on tetanic force, maximum Ca2+-activated force, and membrane potential were largely prevented by 1 mM Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a membrane-permeable superoxide dismutase mimetic, indicating that the increased O2•− production at physiological temperatures is largely responsible for the observed depression in tetanic force at 37°C by affecting the contractile apparatus and plasma membrane.
Transport and regulatory characteristics of the yeast bicarbonate transporter homolog Bor1p
Authors: Jennings Michael L. , Howren Todd R. , Cui Jian , Winters Maria , Hannigan Robyn
Published: April 2007

The functional properties of the Saccharomyces cerevisiae bicarbonate transporter homolog Bor1p (YNL275wp) were characterized by measuring boron (H3BO3), Na+, and Cl− fluxes. Neither Na+ nor Cl− appears to be a transported substrate for Bor1p. Uphill efflux of boron mediated by Bor1p was demonstrated directly by loading cells with boron and resuspending in a low-boron medium. Cells with intact BOR1, but not the deletant strain, transport boron outward until the intracellular concentration is sevenfold lower than that in the medium. Boron efflux through Bor1p is a saturable function of intracellular boron (apparent Km ∼1–2 mM). The extracellular pH dependences of boron distribution and efflux indicate that uphill efflux is driven by the inward H+ gradient. Addition of 30 mM HCO3− does not affect boron extrusion by Bor1p, indicating that HCO3− does not participate in Bor1p function. Functional Bor1p is present in cells grown in medium with no added boron, and overnight growth in 10 mM H3BO3 causes only a small increase in the levels of functional Bor1p and in BOR1 mRNA. The fact that Bor1p is expressed when there is no need for boron extrusion and is not strongly induced in the presence of growth-inhibitory boron concentrations is surprising if the main physiological function of yeast Bor1p is boron efflux. A possible role in vacuolar dynamics for Bor1p was recently reported by Decker and Wickner ( 10 ). Under the conditions used presently, there appears to be mildly abnormal vacuolar morphology in the deletant strain.
A mathematical model of plasma membrane electrophysiology and calcium dynamics in vascular endothelial cells
Authors: Silva Haroldo S. , Kapela Adam , Tsoukias Nikolaos M.
Published: April 2007

Vascular endothelial cells (ECs) modulate smooth muscle cell (SMC) contractility, assisting in vascular tone regulation. Cytosolic Ca2+concentration ([Ca2+]i) and membrane potential ( Vm) play important roles in this process by controlling EC-dependent vasoactive signals and intercellular communication. The present mathematical model integrates plasmalemma electrophysiology and Ca2+dynamics to investigate EC responses to different stimuli and the controversial relationship between [Ca2+]iand Vm. The model contains descriptions for the intracellular balance of major ionic species and the release of Ca2+from intracellular stores. It also expands previous formulations by including more detailed transmembrane current descriptions. The model reproduces Vmresponses to volume-regulated anion channel (VRAC) blockers and extracellular K+concentration ([K+]o) challenges, predicting 1) that Vmchanges upon VRAC blockade are [K+]odependent and 2) a biphasic response of Vmto increasing [K+]o. Simulations of agonist-induced Ca2+mobilization replicate experiments under control and Vmhyperpolarization blockade conditions. They show that peak [Ca2+]iis governed by store Ca2+release while Ca2+influx (and consequently Vm) impacts more the resting and plateau [Ca2+]i. The Vmsensitivity of rest and plateau [Ca2+]iis dictated by a [Ca2+]i“buffering” system capable of masking the Vm-dependent transmembrane Ca2+influx. The model predicts plasma membrane Ca2+-ATPase and Ca2+permeability as main players in this process. The heterogeneous Vmimpact on [Ca2+]imay elucidate conflicting reports on how Vminfluences EC Ca2+. The present study forms the basis for the development of multicellular EC-SMC models that can assist in understanding vascular autoregulation in health and disease.
Disruption of function and localization of tight junctional structures and Mrp2 in sustained estradiol-17β-d-glucuronide-induced cholestasis
Authors: Mottino Aldo D. , Hoffman Tim , Crocenzi Fernando A. , Sánchez Pozzi Enrique J. , Roma Marcelo G. , Vore Mary
Published: April 2007

Estradiol-17β-d-glucuronide (E217G) induces immediate and profound but transient cholestasis in rats when administered as a single bolus dose. Here, we examined the consequence of sustained E217G cholestasis and assessed the function and localization of the tight junctional proteins zonula occludens-1 (ZO-1) and occludin and of the canalicular transporter multidrug resistance-associated protein-2 (Mrp2). An initial dose of E217G (15 μmol/kg iv) followed by five subsequent doses of 7.5 μmol/kg from 60 to 240 min induced a sustained 40–70% decrease in bile flow. Following their biliary retrograde administration, cholera toxin B subunit-FITC or horseradish peroxidase were detected at the sinusoidal domain, indicating opening of the paracellular route; this occurred as early as 15 min after the first dose as well as 15 min after the last dose of E217G, but not following the administration of vehicle in controls. Localization of ZO-1 and occludin was only slightly affected under acute cholestatic conditions but was severely disrupted under sustained cholestasis, with their appearance suggesting a fragmented structure. Endocytic internalization of Mrp2 to the pericanalicular region was apparent 20 min after a single E217G administration; however, Mrp2 was found more deeply internalized and partially redistributed to the basolateral membrane under sustained cholestasis. In conclusion, acute E217G-induced cholestasis increased permeability of the tight junction, while sustained cholestasis provoked a significant redistribution of ZO-1, occludin, and Mrp2 in addition to increased permeability of the tight junction. Altered tight junction integrity likely contributes to impaired bile secretion and may be causally related to changes in Mrp2 localization.
Intermittent hypoxia reduces upper airway stability in lean but not obese Zucker rats
Authors: Ray Andrew D. , Magalang Ulysses J. , Michlin Charles P. , Ogasa Toshiyuki , Krasney John A. , Gosselin Luc E. , Farkas Gaspar A.
Published: April 2007

Obstructive sleep apnea involves intermittent periods of airway occlusions that lead to repetitive oxygen desaturations. Exposure to chronic intermittent hypoxia (IH) in rats increases diurnal blood pressure and alters skeletal muscle physiology. The impact of IH on upper airway muscle function is unknown. We hypothesize that IH exposure increases upper airway collapsibility in rats due to alterations of the muscles surrounding the upper airway. Lean and obese rats were exposed to cyclic alterations in O2 levels (20.6%-5%) every 90 s, 8 h/day for 6 days/wk for 12 wk. Following the exposure period, arterial pressure was recorded via the tail artery in conscious unrestrained rats. Mean arterial pressure was increased in lean IH but not in obese IH-exposed Zucker rats ( P < 0.05). The pharyngeal pressure associated with airway collapse (Pcrit) was measured under anesthesia during baseline conditions and then during supramaximal stimulation of the hypoglossal nerve (cnXII). Baseline Pcrit was more positive (more collapsible) in lean but not obese rats following 12 wk of IH ( P < 0.05), while supramaximal stimulation of cnXII increased airway stability (decreased Pcrit) in both lean and obese Zucker rats following IH to levels that were similar to their respective room air controls. The in vitro peak tension and the expression of the individual myosin heavy chain isoforms from the upper airway muscles were unaltered following IH. We conclude that IH leads to increases in baseline collapsibility in lean Zucker rats exposed to IH by nonmyogenic mechanisms.
Adrenalectomy alters regulation of blood pressure and endothelial nitric oxide synthase in sheep: modulation by estradiol
Authors: Li Feng , Wood Charles E. , Keller-Wood Maureen
Published: April 2007

Hypoadrenocorticism produces more severe hypotension during the peripartal period in pregnant ewes and women. We hypothesized that estradiol increases the severity of hypotension after withdrawal of corticosteroids and that this results from combined effects of adrenalectomy and estradiol to increase endothelial nitric oxide synthase (eNOS). In study I, blood pressure and eNOS mRNA and protein in aorta, uterine, renal, and mesenteric arteries were measured in intact ewes or adrenalectomized ewes 18–20 h after cessation of infusion of cortisol and aldosterone; half of each group ewes were treated with estradiol. In study II, adrenalectomized ewes were similarly studied 22–28 h after withdrawal of corticosteroids. Estradiol treatment in both studies significantly increased eNOS mRNA and protein in uterine artery, whereas corticosteroid withdrawal decreased expression of eNOS mRNA and protein in uterine artery. In both studies, adrenalectomy and steroid withdrawal decreased mean arterial pressure. In study II, four of six adrenalectomized ewes not treated with estradiol showed dramatic phasic variations in blood pressure and heart rate with a period of ∼20 s, developing within 22–28 h after corticosteroid withdrawal. Although there was no effect of estradiol on blood pressure in study I, in study II, ewes treated with estradiol did not develop this pattern. Estradiol also slowed both the decline in plasma sodium and the rise in plasma potassium after corticosteroid withdrawal. These results disprove the hypothesis that estradiol increases the severity of hypotension during hypoadrenocorticism. However, the study reveals an important effect of corticosteroid withdrawal on blood pressure, consistent with corticosteroid modulation of baroreflex responsiveness.
Oxidative stress as a common pathway to chronic tubulointerstitial injury in kidney allografts
Authors: Djamali Arjang
Published: April 2007

A major challenge for kidney transplantation is to dissect out the identifiable causes of chronic allograft tubulointerstitial fibrosis and to develop cause-specific treatment strategies. There has been a recent interest in the role of oxidative stress (OS) as a mediator of injury in chronic allograft tubular atrophy (TA) and interstitial fibrosis (IF). A review of the literature and data from my laboratory studying chronic allograft TA/IF in rat, rhesus monkey, and human kidneys suggests that OS is increased in graft-infiltrating macrophages, activated myofibroblasts, interstitium, and areas of tubular injury. Chronic allograft OS may be induced by inflammation, abnormal tissue oxygenation, immunosuppressant drugs, and comorbid clinical conditions including diabetes, hypertension, proteinuria, anemia, and dyslipidemia. Moreover, OS-induced chronic TA/IF is associated with signaling pathways including inflammation, apoptosis, hypoxia, and epithelial-to-mesenchymal transition. Most of these injury pathways participate in a self-perpetuating cycle with OS. In conclusion, evidence suggests that OS is a common mechanism of injury in chronic allograft TA/IF. However, most available data demonstrate a correlation and no causal relationship. Furthermore, the extent to which TA/IF is dependent on OS is unknown. These questions may be answered by prospective randomized placebo-control trials examining the role of select antioxidants in the prevention of chronic allograft TA/IF.
Involvement of the CDK2-E2F1 pathway in cisplatin cytotoxicity in vitro and in vivo
Authors: Yu Fang , Megyesi Judit , Safirstein Robert L. , Price Peter M.
Published: April 2007

E2F1 is a key regulator that links cell cycle progression and cell death. E2F1 activity is controlled by Cdk2-cyclin complexes via several mechanisms, such as phosphorylation of retinoblastoma protein (pRb) to release E2F1, direct phosphorylation, and stable physical interaction. We have demonstrated that cisplatin cytotoxicity depends on Cdk2 activity, and Cdk2 inhibition protects kidney cells from cisplatin-induced cell death in vitro and in vivo. Now we show that E2F1 is an important downstream effector of Cdk2 that accumulates in mouse kidneys and in cultured mouse proximal tubular cells (TKPTS) after cisplatin exposure by a Cdk2-dependent mechanism. Direct inhibition of E2F1 by transduction with adenoviruses expressing an E2F1-binding protein (TopBP1) protected TKPTS cells from cisplatin-induced apoptosis, whereas overexpression of E2F1 caused cell death. Moreover, E2F1 knockout mice were markedly protected against cisplatin nephrotoxicity by both functional and histological criteria. Collectively, cisplatin-induced cell death is dependent on Cdk2 activity, which is at least partly through the Cdk2-E2F1 pathway both in vitro and in vivo.
Lack of a role of membrane-protein interactions in flow-dependent activation of ENaC
Authors: Carattino Marcelo D. , Liu Wen , Hill Warren G. , Satlin Lisa M. , Kleyman Thomas R.
Published: April 2007

Rates of Na+absorption in the distal nephron increase proportionally with the rates of tubular flow. We tested the hypothesis that the deformation or tension generated in the plasma membrane in response to flow activates the epithelial sodium channel (ENaC). We modified the physical properties of the membrane by changing the temperature and the content of cholesterol. Rates of net Na+absorption measured in cortical collecting ducts (CCDs) perfused at room temperature at slow (∼1) and fast (∼5 nl·min−1·mm−1) flow rates were less than those measured at 37°C at the same flow rates, although increases in tubular fluid flow rates led to comparable relative increases in net Na+absorption at both temperatures. Xenopus laevis oocytes expressing ENaC responded to an increase in shear stress at 22–25°C with a discrete delay followed by a monoexponential increase in whole-cell Na+currents. We observed that temperature affected 1) basal currents, 2) delay times, 3) kinetics of activation, and 4) fold-increase in macroscopic currents in response to flow. The magnitude of the response to flow displayed biphasic behavior as a function of temperature, with a minimal value at 25°C. Steady-state fluorescence anisotropic measurements of purified plasma membranes did not show any obvious phase transition behavior over a temperature range from 8.3°C to 36.5°C. Modification of the content of membrane cholesterol did not affect the response to flow. Our results suggest that the flow-dependent activation of ENaC is not influenced by modifications in the intrinsic properties of the plasma membrane.
AMP deaminase deficiency is associated with lower sprint cycling performance in healthy subjects
Authors: Fischer Heléne , Esbjörnsson Mona , Sabina Richard L. , Strömberg Anna , Peyrard-Janvid Myriam , Norman Barbara
Published: April 2007

AMP deaminase (AMPD) deficiency is an inherited disorder of skeletal muscle found in ∼2% of the Caucasian population. Although most AMPD-deficient individuals are asymptomatic, a small subset has exercise-related cramping and pain without any other identifiable neuromuscular complications. This heterogeneity has raised doubts about the physiological significance of AMPD in skeletal muscle, despite evidence for disrupted adenine nucleotide catabolism during exercise in deficient individuals. Previous studies have evaluated the effect of AMPD deficiency on exercise performance with mixed results. This study was designed to circumvent the perceived limitations in previous reports by measuring exercise performance during a 30-s Wingate test in 139 healthy, physically active subjects of both sexes, with different AMPD1 genotypes, including 12 AMPD-deficient subjects. Three of the deficient subjects were compound heterozygotes characterized by the common c.34C>T mutation in one allele and a newly discovered AMPD1 mutation, c.404delT, in the other. While there was no significant difference in peak power across AMPD1 genotypes, statistical analysis revealed a faster power decrease in the AMPD-deficient group and a difference in mean power across the genotypes ( P = 0.0035). This divergence was most striking at 15 s of the 30-s cycling. Assessed by the fatigue index, the decrease in power output at 15 s of exercise was significantly greater in the deficient group compared with the other genotypes ( P = 0.0006). The approximate 10% lower mean power in healthy AMPD-deficient subjects during a 30-s Wingate cycling test reveals a functional role for the AMPD1 enzyme in sprint exercise.
Preexercise sodium loading aids fluid balance and endurance for women exercising in the heat
Authors: Sims Stacy T. , Rehrer Nancy J. , Bell Melanie L. , Cotter James D.
Published: April 2007

This study was conducted during the high-hormone phase of both natural and oral contraceptive pill (OCP)-mediated menstrual cycles to determine whether preexercise ingestion of a concentrated sodium beverage would increase plasma volume (PV), reduce physiological strain, and aid endurance of moderately trained women cycling in warm conditions. Thirteen trained cyclists [peak O2 uptake 52 ml·kg−1·min−1 (SD 2), age 26 yr (SD 6), weight 60.8 kg (SD 5)] who were oral contraceptive users ( n = 6) or not ( n = 7) completed this double-blind, crossover experiment. Cyclists ingested a concentrated-sodium (High Na+: 164 mmol Na+/l) or low-sodium (Low Na+: 10 mmol Na+/l) beverage (10 ml/kg) before cycling to exhaustion at 70% Peak O2 uptake in warm conditions (32°C, 50% relative humidity, air velocity 4.5 m/s). Beverage (∼628 ml) was ingested in seven portions across 60 min beginning 105 min before exercise, with no additional fluid given until the end of the trial. Trials were separated by one to two menstrual cycles. High Na+ increased PV (calculated from hematocrit and hemoglobin concentration) before exercise, whereas Low Na+ did not [−4.4 (SD 1.1) vs. −1.9% (SD 1.3); 95% confidence interval: for the difference 5.20, 6.92; P < 0.0001], and it involved greater time to exhaustion [98.8 (SD 25.6) vs. 78.7 (SD 24.6) min; 95% confidence interval: 13.3, 26.8; P < 0.0001]. Core temperature rose more quickly with Low Na+ [1.6°C/h (SD 0.2)] than High Na+ [1.2°C/h (SD 0.2); P = 0.04]. Plasma [AVP], [Na+] concentration, and osmolality, and urine volume, [Na+], and osmolality decreased with sodium loading ( P < 0.05) independent of pill usage. Thus preexercise ingestion of a concentrated sodium beverage increased PV, reduced thermoregulatory strain, and increased exercise capacity for women in the high-hormone phase of natural and oral contraceptive pill-mediated menstrual cycles, in warm conditions.
GABAergic Pump Cells of Solitary Tract Nucleus Innervate Retrotrapezoid Nucleus Chemoreceptors
Authors: Takakura Ana C. , Moreira Thiago S. , West Gavin H. , Gwilt Justin M. , Colombari Eduardo , Stornetta Ruth L. , Guyenet Patrice G.
Published: April 2007

The retrotrapezoid nucleus (RTN) contains central respiratory chemoreceptors that are inhibited by activation of slowly adapting pulmonary stretch receptors (SARs). Here we examine whether RTN inhibition by lung inflation could be mediated by a direct projection from SAR second-order neurons (pump cells). Pump cells ( n = 56 neurons, 13 rats) were recorded in the nucleus of solitary tract (NTS) of halothane-anesthetized rats with intact vagus nerves. Pump cells had discharges that coincided with lung inflation as monitored by the tracheal pressure. Their activity increased when end-expiratory pressure was raised and stopped instantly when ventilation was interrupted in expiration. Many pump cells could be antidromically activated from RTN (12/36). Nine of those were labeled with biotinamide. Of these nine cells, eight contained glutamic acid decarboxylase 67 (GAD67) mRNA and seven were found to reside in the lower half of the interstitial subnucleus of NTS (iNTS). Using the retrograde tracer cholera toxin-B, we confirmed that neurons located in or close to iNTS innervate RTN (two rats). Many such neurons contained GAD67 mRNA and a few contained glycine transporter2 (GLYT2) mRNA. Anterograde tract tracing with biotinylated dextranamide (four rats) applied to iNTS also confirmed that this region innervates RTN by a predominantly GABAergic projection. This work confirms that many rat NTS pump cells are located in and around the interstitial subnucleus at area postrema level. We demonstrate that a GABAergic subset of these pump cells innervates the RTN region. We conclude that these inhibitory neurons probably contact RTN chemoreceptors and mediate their inhibition by lung inflation.
Ion Channel Compartments in Photoreceptors: Evidence From Salamander Rods With Intact and Ablated Terminals
Authors: MacLeish Peter R. , Nurse Colin A.
Published: April 2007

Vertebrate photoreceptors are highly polarized sensory cells in which several different ionic currents have been characterized. In the present study we used whole cell voltage-clamp and optical imaging techniques, the former combined with microsurgical manipulations, and simultaneous recording of membrane current and intracellular calcium signals to investigate the spatial distribution of ion channels within isolated salamander rods. In recordings from intact rods with visible terminals, evidence for five previously identified ionic currents was obtained. These include two Ca2+-dependent, i.e., a Ca2+-dependent chloride current [ ICl(Ca)] and a large-conductance Ca2+- and voltage-dependent K+or BK current [ IK(Ca)], and three voltage-dependent currents, i.e., a delayed-rectifier type current [ IK(V)], a hyperpolarization-activated cation current ( Ih), and a dihydropyridine-sensitive L-type calcium current ( ICa). Of these, ICl(Ca)was highly correlated with the presence of a terminal; rods with visible terminals expressed ICl(Ca)without exception ( n = 125), whereas approximately 71% of rods (40/56) without visible terminals lacked ICl(Ca). More significantly, ICl(Ca)was absent from all rods ( n = 33) that had their terminals ablated, and recordings from the same cell before and after terminal ablation led, in all cases ( n =10), to the loss of ICl(Ca). In contrast, IK(Ca), IK(V), and Ihremained largely intact after terminal ablation, suggesting that they arose principally from ion channels located in the soma and/or inner segment. The outward IK(Ca)in terminal-ablated rods was reversibly suppressed on “puffing” a Ca2+-free extracellular solution over the soma and was appreciably enhanced by the L-type Ca2+channel agonist, Bay K 8644 (0.1–2 μM). These data indicate that rod photoreceptors possess discrete targeting mechanisms that preferentially sort ion channels mediating ICl(Ca)to the terminal.
Subthalamic Stimulation and Neuronal Activity in the Substantia Nigra in Parkinson's Disease
Authors: Maltête D. , Jodoin N. , Karachi C. , Houeto J. L. , Navarro S. , Cornu P. , Agid Y. , Welter M. L.
Published: April 2007

High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for severe forms of Parkinson's disease (PD). To study the effects of high-frequency STN stimulation on one of the main output pathways of the basal ganglia, single-unit recordings of the neuronal activity of the substantia nigra pars reticulata (SNr) were performed before, during, and after the application of STN electrical stimulation in eight PD patients. During STN stimulation at 14 Hz, no change in either the mean firing rate or the discharge pattern of SNr neurons was observed. STN stimulation at 140 Hz decreased the mean firing rate by 64% and the mean duration of bursting mode activity of SNr neurons by 70%. The SNr residual neuronal activity during 140-Hz STN stimulation was driven by the STN stimulation. How the decrease in rate and modification of firing pattern of SNr-evoked neural activity, during high-frequency STN stimulation, contribute to the improvement of parkinsonian motor disability remains to be elucidated.
Preparation of Anticipatory Postural Adjustments Prior to Stepping
Authors: MacKinnon Colum D. , Bissig Dennis , Chiusano Julie , Miller Emily , Rudnick Laura , Jager Candice , Zhang Yunhui , Mille Marie-Laure , Rogers Mark W.
Published: April 2007

Step initiation involves anticipatory postural adjustments (APAs) that propel the body mass forward and laterally before the first step. This study used a startle-like acoustic stimulus (SAS) and transcranial magnetic stimulation (TMS) to examine the preparation of APAs before forward stepping. After an instructed delay period, subjects initiated forward steps in reaction to a visual “go” cue. TMS or SAS was delivered before (−1,400 or −100 ms), on (0 ms), or after (+100 ms for TMS, +200 ms for SAS) the imperative “go” cue. Ground reaction forces and electromyographic activity were recorded. In control trials, the mean reaction time was 217 ± 38 ms. In contrast, the SAS evoked APAs that had an average onset of 110 ± 54 ms, whereas the incidence, magnitude, and duration of the APA increased as the stimulus timing approached the “go” cue. A facilitation of motor-evoked potentials in the initial agonist muscle was observed only when TMS was applied at +100 ms. These findings indicate that there was an initial phase of movement preparation during which the APA-stepping sequence was progressively assembled, and that this early preparation did not involve the corticomotor pathways activated by TMS. The subsequent increase in corticomotor excitability between the imperative stimulus and onset of the APA suggests that corticospinal pathways contribute to the voluntary initiation of the prepared APA-stepping sequence. These findings are consistent with a feedforward mode of neural control whereby the motor sequence, including the associated postural adjustments, is prepared before voluntary movement.
Plasticity in the Rat Posterior Auditory Field Following Nucleus Basalis Stimulation
Authors: Puckett Amanda C. , Pandya Pritesh K. , Moucha Raluca , Dai WeiWei , Kilgard Michael P.
Published: April 2007

Classical conditioning paradigms have been shown to cause frequency-specific plasticity in both primary and secondary cortical areas. Previous research demonstrated that repeated pairing of nucleus basalis (NB) stimulation with a tone results in plasticity in primary auditory cortex (A1), mimicking the changes observed after classical conditioning. However, few studies have documented the effects of similar paradigms in secondary cortical areas. The purpose of this study was to quantify plasticity in the posterior auditory field (PAF) of the rat after NB stimulation paired with a high-frequency tone. NB–tone pairing increased the frequency selectivity of PAF sites activated by the paired tone. This frequency-specific receptive field size narrowing led to a reorganization of PAF such that responses to low- and mid-frequency tones were reduced by 40%. Plasticity in A1 was consistent with previous studies—pairing a high-frequency tone with NB stimulation expanded the high-frequency region of the frequency map. Receptive field sizes did not change, but characteristic frequencies in A1 were shifted after NB–tone pairing. These results demonstrate that experience-dependent plasticity can take different forms in both A1 and secondary auditory cortex.
Descent methods for convex optimization problems in Banach spaces
Authors: Ali M. S. S.
Published: April 2007

We consider optimization problems in Banach spaces, whose cost functions are convex and smooth, but do not possess strengthened convexity properties. We propose a general class of iterative methods, which are based on combining descent and regularization approaches and provide strong convergence of iteration sequences to a solution of the initial problem.
Some chain conditions on weak incidence algebras
Authors: Singh Surjeet , Al-Thukair Fawzi
Published: April 2007

Let X be any partially ordered set, R any commutative ring, and T = I∗(X, R) the weak incidence algebra of X over R. Let Z be a finite nonempty subset of X, L(Z) = {x ∈ X : x ≤ z   for some   z ∈ Z}, and M = Tez. Various chain conditions on M are investigated. The results so proved are used to construct some classes of right perfect rings that are not left perfect.
Gleason‐kahane‐Żelazko theorem for spectrally bounded algebra
Authors: Kulkarni S. H. , Sukumar D.
Published: April 2007

We prove by elementary methods the following generalization of a theorem due to Gleason, Kahane, and Żelazko. Let A be a real algebra with unit 1 such that the spectrum of every element in A is bounded and let φ : A → ℂ be a linear map such that φ(1) = 1 and (φ(a)) 2 + (φ(b)) 2 ≠ 0 for all a, b in A satisfying ab = ba and a2 + b2 is invertible. Then φ(ab) = φ(a)φ(b) for all a, b in A. Similar results are proved for real and complex algebras using Ransford′s concept of generalized spectrum. With these ideas, a sufficient condition for a linear transformation to be multiplicative is established in terms of generalized spectrum.
Smarandache BCC‐algebras
Authors: Jun Young Bae
Published: April 2007

The notions of Smarandache BCC‐algebras and Smarandache BCC‐ideals are introduced. Conditions for a (special) subset to be a Smarandache BCC‐ideal are given.
K‐Bessel functions associated to a 3‐rank Jordan algebra
Authors: Dib Hacen
Published: April 2007

Using the Bessel‐Muirhead system, we can express the K‐Bessel function defined on a Jordan algebra as a linear combination of the J‐solutions. We determine explicitly the coefficients when the rank of this Jordan algebra is three after a reduction to the rank two. The main tools are some algebraic identities developed for this occasion.
Invariance of the Cauchy mean‐value expression with an application to the problem of representation of Cauchy means
Authors: Berrone Lucio R.
Published: April 2007

The notion of invariance under transformations (changes of coordinates) of the Cauchy mean‐value expression is introduced and then used in furnishing a suitable two‐variable version of a result by L. Losonczi on equality of many‐variable Cauchy means. An assessment of the methods used by Losonczi and Matkowski is made and an alternative way is proposed to solve the problem of representation of two‐variable Cauchy means.
On completeness of quasi‐pseudometric spaces
Authors: Moshokoa Seithuti P.
Published: April 2007

We discuss completeness in terms of a notion of absolute closure. This will be done in the context of separated quasi‐pseudometric spaces and bitopological spaces. The notion is equivalent to the classical notion of completeness when restricted to the class of metric spaces.
Idempotent‐separating extensions of regular semigroups
Authors: Tamilarasi A.
Published: April 2007

For a regular biordered set E, the notion of E‐diagram and the associated regular semigroup was introduced in our previous paper (1995). Given a regular biordered set E, an E‐diagram in a category C is a collection of objects, indexed by the elements of E and morphisms of C satisfying certain compatibility conditions. With such an E‐diagram A we associate a regular semigroup RegE(A) having E as its biordered set of idempotents. This regular semigroup is analogous to automorphism group of a group. This paper provides an application of RegE(A) to the idempotent‐separating extensions of regular semigroups. We introduced the concept of crossed pair and used it to describe all extensions of a regular semigroup S by a group E‐diagram A. In this paper, the necessary and sufficient condition for the existence of an extension of S by A is provided. Also we study cohomology and obstruction theories and find a relationship with extension theory for regular semigroups.
Searching for Kaprekar′s constants: algorithms and results
Authors: Walden Byron L.
Published: April 2007

We examine some new results on Kaprekar′s constants, specifically establishing the unique 7‐digit (in base 4) and 9‐digit (in base 5) Kaprekar′s constants and showing that there are no 15‐, 21‐, 27‐, or 33‐digit Kaprekar′s constants.
On quasi‐ideals and bi‐ideals in ternary semirings
Authors: Kar S.
Published: April 2007

We introduce the notions of quasi‐ideal and bi‐ideal in ternary semirings and study some properties of these two ideals. We also characterize regular ternary semiring in terms of these two subsystems of ternary semirings.
Finite element least‐squares methods for a compressible stokes system
Authors: Kim Keehwan , Kim Sangdong , Shin Sangsik
Published: April 2007

The least‐squares functional related to a vorticity variable or a velocity flux variable is considered for two‐dimensional compressible Stokes equations. We show ellipticity and continuity in an appropriate product norm for each functional.
On a higher‐order evolution equation with a Stepanov‐bounded solution
Authors: Rao Aribindi Satyanarayan
Published: April 2007

We study strong solutions u : ℝ → X, a Banach space X, of the nth‐order evolution equation u(n) − Au(n−1) = f, an infinitesimal generator of a strongly continuous group A : D(A)⊆X → X, and a given forcing term f : ℝ → X. It is shown that if X is reflexive, u and u(n−1) are Stepanov‐bounded, and f is Stepanov almost periodic, then u and all derivatives u′, …, u(n−1) are strongly almost periodic. In the case of a general Banach space X, a corresponding result is obtained, proving weak almost periodicity of u, u′, …, u(n−1).
On smooth fuzzy subspaces
Authors: Abbas S. E.
Published: April 2007

We introduce a new concept of smooth topological subspaces, which
coincides with the usual definition in the case where
μ = χY, Y ⊂ X. Also, we introduce some concepts such
as q‐nbd systems, continuity, separation
axioms, compactness, and connectedness in this sense. Also,
various characterization for some fuzzy topological concepts in
this sense are given.
On the genus of free loop fibrations over F0‐spaces
Authors: Yamaguchi Toshihiro
Published: April 2007

We give a lower bound of the genus of the fibration
of free loops on an elliptic space whose rational cohomology
is concentrated in even degrees.
Asymptotic solution of nonlinear moment equations for constant‐rate aerosol reactors
Authors: Shaw B. D.
Published: April 2007

Nonlinear evolution equations based upon moments of the aerosol size distribution function are solved asymptotically for constant‐rate aerosol reactors (i.e., where condensible monomer
is added at a constant rate) operating in the free‐molecular limit. The governing equations are nondimensionalized and a large parameter that controls nucleation behavior is identified. Asymptotic analyses are developed in terms of this parameter. Comparison of the asymptotic results with direct numerical integration of the governing equations is favorable. The asymptotic results provide a simplified analytical approach to estimating average particle sizes, particle number densities, and peak supersaturation values for constant‐rate aerosol reactors.