bluuebunny/crossref_metadata_2025 huggingface dataset:
A GAME-THEORETIC TREATMENT OF A TIME-DISCRETE EMISSION REDUCTION MODEL
Authors: KRABS WERNER , PICKL STEFAN
Published: May 2004

We present a game-theoretic treatment of the so-called TEM model which leads to new results in the area of time-discrete dynamical games. The presented TEM-model describes the economical interaction between several actors (players) who intend to minimize their emissions (Ei) caused by technologies (Ti) by means of expenditures of money (Mi) or financial means, respectively. The index stands for the ith player, i=1,…,n.

The players are linked by technical cooperations and the market, which expresses itself in the nonlinear time-discrete dynamics of the Technology-Emissions-Means-model, in short: TEM-model. In the sense of environmental protection, the aim is to reach a state which is mentioned in the Kyoto Protocol by choosing the control parameters such that the emissions of each player become minimized. The focal point is the realization of the necessary optimal control parameters via a played cost game, which is determined by the way of cooperation of the actors.

In application to the work of G. Leitmann [1974], but not regarding solution sets as feasible sets, the τ-value of S. H. Tijs and T. S. H. Driessen [1986] is taken as a control parameter. This leads to a new class of problems in the area of 1-convex games. We want to solve the problem by a non-cooperative and cooperative treatment. We prove that the core which is gained by cooperation of the players is nonempty and can be used as feasible set for our control problem.

With this solution a reasonable model for a Joint-Implementation process is developed, where its necessary fund is represented by the non-empty core of the analyzed game. Steering with parameters of this feasible set, the TEM-model can be regarded as a useful tool to implement and verify a technical Joint-Implementation Program.

For the necessary data given to the Clearing House () we are able to compare the numerical results with real world phenomena.
SHARING THE BENEFITS OF COOPERATION IN THE NORWEGIAN SPRING-SPAWNING HERRING FISHERY
Authors: LINDROOS MARKO
Published: May 2004

The purpose of this paper is to study the sharing of cooperative benefits between the potential fishing nations of Norwegian spring-spawning (or Atlanto-Scandian) herring (NSSH). I study a three-player coalitional game where Shapley value is used as a solution concept. The results show that full cooperation is a stable solution of the game, that is, no country finds it optimal to leave the grand coalition. However, it is further shown how full cooperation may become unstable under biological uncertainty. Therefore, I propose a simple mechanism to alleviate the problem. The instability created by biological uncertainty can be significantly reduced when simple modified cooperative strategies are applied. By introducing a safe minimum biological level for the fish stock (SMBL) below which no harvesting takes place and also changing gear selectivities, instability reduces a great deal. However, a safe minimum economic level (SMEL) when there may be perfect stability is shown to be higher than the SMBL.
WHEN TO RATIFY AN ENVIRONMENTAL AGREEMENT: THE CASE OF HIGH SEAS FISHERIES
Authors: KAITALA VEIJO , LINDROOS MARKO
Published: May 2004

We investigate in this paper the optimal timing of cooperative agreements dealing with the harvesting, utilisation or management of marine fish resources. We formulate the optimal timing problem as a two-player dynamic differential game model where both players, e.g. harvesting countries, consider the timing of the agreement as a strategic decision parameter. In other words, the initialisation of the environmental agreement will be subjected to negotiations. The game begins by a period during which the players negotiate on the cooperative agreement. During this period the players optimize their fishing unilaterally, that is, they play a non-cooperative game taking into account that they will enter a cooperative fishery some time later. It is up to the players to decide when they wish to initiate cooperation. We show that there are several possibilities where cooperation is never an option for at least one of the countries. In other cases immediate cooperation may be optimal for both countries. Between these extreme cases is the possibility of some delay in entering cooperation. The determinants of willingness to cooperate in the game include unit costs of harvesting, discount rate, maximum fishing efforts, initial stock size, biological growth rate, carrying capacity and division of profits.
THE G-FUNCTION METHOD FOR ANALYZING DARWINIAN DYNAMICS
Authors: VINCENT THOMAS L.
Published: May 2004

Darwinian dynamics refers to the dynamical processes underlying natural selection that drives evolution. We are interested in the evolution of strategies used by biological entities. There are two dynamical processes involved, population dynamics (relationship between population density and the agents affecting density) and strategy dynamics (relationship between strategy values and the agents affecting these values). Darwinian dynamics is a total dynamic obtained through the coupling of these two processes, the modeling of which, involves dynamical systems, optimization, stability, and game theory. Using a method called the G-function approach, we explore how an evolutionary process can take place in a set of differential equations, and we examine some interesting links between evolutionary stability and optimization as embodied in the ESS maximum principle. One of the interesting paradoxes is how a "hill-climbing" algorithm can end up at a stable local minimum and why this might have important implications in understanding speciation (the creation of new species from a homogeneous population). Finally, we will examine how these concepts are currently being applied to model the development of tumors in humans.
VIABLE CAPTURE BASIN FOR STUDYING DIFFERENTIAL AND HYBRID GAMES: APPLICATION TO FINANCE
Authors: SAINT-PIERRE PATRICK
Published: May 2004

Viability theory can be applied for determining viable capture basin for control problem in presence of uncertainty. We first recall the concepts of viability theory which allow to develop numerical methods for computing viable capture basin for control problems and guaranteed control problems. Recent developments of option pricing in the framework of dynamical games with constraints lead to the formulation of guaranteed valuation in terms of guaranteed viable-capture basin of a dynamical game. As an application we show how the viability/capturability algorithm evaluates and manages portfolios. Regarding viability/capturability issues, stochastic control is a particular use of tychastic control. We replace the standard translation of uncertainty by stochastic control problem by tychastic ones and the concept of stochastic viability by the one of guaranteed viability kernel. Considering the Cox–Rubinstein model, we extend algorithms for hedging portfolios in the presence of transaction costs and dividends using recent developments on hybrid calculus.
NEW APPROACH TO THE COLLISION AVOIDANCE PROBLEM FOR A SHIP
Authors: MIELE A. , WANG T.
Published: May 2004

A new algorithm is developed to solve the collision avoidance problem for a host ship subject to kinematic, dynamic, and moment equations and steered via rudder under the assumptions that the rudder angle and rudder angle time rate are subject to upper and lower bounds. The objective of the collision avoidance maneuver is to maximize with respect to the state and control history the timewise minimum distance between a host ship and an intruder ship. Two limiting cases are considered: (i) the intruder ship is uncooperative and keeps its course unchanged during the encounter; (ii) the intruder ship is cooperative. In both cases, a differential game formulation is avoided and the collision avoidance problem is formulated as a maximin problem of optimal control.

Four problems are investigated and their solutions compared: Problems P1 and P2 deal with uncooperative collision avoidance, while Problems P3 and P4 deal with cooperative collision avoidance.

Numerical results show that the optimal control histories always involve multiple subarcs along which either the rudder angle is kept at one of the extreme positions or the rudder angle time rate is held at one of the extreme values.
MULTISTAGE COOPERATIVE GAMES AND PROBLEM OF TIME CONSISTENCY
Authors: ZAKHAROV VICTOR , DEMENTIEVA MARIA
Published: May 2004

In this paper we consider the problem of time-consistency of the subcore in a multistage TU-cooperative game. We propose necessary and sufficient conditions for the time-consistency of an imputation from the subcore. Based on these conditions, we suggest an algorithm providing time-consistency of a selector of the subcore. Besides, we prove consistency of the subcore with respect to the MDM-reduction. Finally we introduce the notions of reduced game and dynamic consistency for multistage cooperative games. One of the main results of this paper is a theorem stating some properties of dynamic consistency of the subcore selectors. We focus particularly on the conditions of the dynamic consistency of the subcore with respect to the MDM-reduced game.
SOME PROPERTIES OF THE BELLMAN–ISAACS EQUATION FOR THE GAMES ON SURFACES OF REVOLUTION
Authors: MELIKYAN ARIK
Published: May 2004

Certain geometrical properties of a dynamic game may generate a situation when in some subspace D of the game space the game value depends only on the coordinates of one of the players. Consequently, that player has a definite optimal behavior, while the other one may exploit an arbitrary control till reaching the boundary of D. In other words, in D one has an optimal control problem rather than a dynamic game. We show that such phenomenon takes place in pursuit-evasion games on a family of 2D surfaces of revolution, including the cones and the hyperboloids of two sheets, due to special convexity properties of the reachability sets of the players. The complete solution of the games on cones one can find in Melikyan [1998], Melikyan, et al. [1998], the games on hyperboloids are investigated in Hovakimyan and Melikyan [2000]. This paper presents new results for the latter games. In the considerations an important role happen to play the focal points, conjugate to the pursuer's positions in the variational problem on geodesic lines.
Prenatal programming of adult thyroid function by alcohol and thyroid hormones
Authors: Slone Wilcoxon Jennifer , Redei Eva E.
Published: May 2004

Increasing evidence associates environmental challenges early in life with permanent alterations of physiological functions in adulthood. These changes in fetal environment can trigger physiological adaptations by the fetus, called fetal programming, which may be beneficial before birth but permanently influence the physiology of the organism. In this study, we investigated the potential connection between alcohol-induced decreased maternal thyroid function and the hypothalamic-pituitary-thyroid (HPT) function of adult rat offspring. Plasma 3,5,3′-triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) levels were decreased in alcohol-consuming (E) dams on gestational day 21 compared with ad libitum- (C) and pair-fed (PF) controls. No significant differences were found in HPT function in young offspring (3 wk of age) between diet groups. However, adult fetal alcohol-exposed (FAE) offspring had significantly decreased levels of T3 along with elevated TSH compared with control offspring. T4 administration to the mother did not normalize the hypothyroid state of the adult FAE offspring. Interestingly, administration of T4 to control pregnant dams decreased plasma T3 of the adult female offspring only, whereas T4 together with maternal alcohol consumption or pair-feeding led to decreased TSH and T4 in the adult female offspring. Our results suggest that ethanol consumption and T4 administration alter maternal HPT function, leading to prenatally programmed permanent alterations in the thyroid function of the adult offspring.
Inflammatory gene expression by human colonic smooth muscle cells
Authors: Salinthone Sonemany , Singer Cherie A. , Gerthoffer William T.
Published: May 2004

Intestinal mucosal cells and invading leukocytes produce inappropriate levels of cytokines and chemokines in human colitis. However, smooth muscle cells of the airway and vasculature also synthesize cytokines and chemokines. To determine whether human colonic myocytes can synthesize proinflammatory mediators, strips of circular smooth muscle and smooth muscle cells were isolated from human colon. Myocytes and muscle strips were stimulated with 10 ng/ml of IL-1β, TNF-α, and IFN-γ, respectively. Expression of mRNA for IL-1β, IL-6, IL-8, and cyclooxygenase-2 (COX-2) was induced within 2 h and continued to increase for 8–12 h. Regulated on activation, normal T cell-expressed and -secreted (RANTES) mRNA expression was slower, appearing at 8 h and increasing linearly through 20 h. Expression of all five mRNAs was inhibited by 0.1 μM MG-132, a proteosome inhibitor that blocks NF-κB activation. Expression of IL-1β, IL-6, IL-8, and COX-2 mRNA was reduced by 30 μM PP1, an Src family tyrosine kinase inhibitor, and by 25 μM SB-203580, a p38 MAPK inhibitor. MAPK/extracellular regulated kinase-1 inhibitor PD-98059 (25 μM) was much less effective. In conclusion, human colonic smooth muscle cells can synthesize and secrete interleukins (IL-1β and IL-6) and chemokines (IL-8 and RANTES) and upregulate expression of COX-2. Regulation of cytokine, chemokine, and COX-2 mRNA depends on multiple signaling pathways, including Src-family kinases, extracellular regulated kinase, p38 MAPKs, and NF-κB. SB-203580 was a consistent, efficacious inhibitor of inflammatory gene expression, suggesting an important role of p38 MAPK in synthetic functions of human colonic smooth muscle.
Salutary effects of androstenediol on cardiac function and splanchnic perfusion after trauma-hemorrhage
Authors: Shimizu Tomoharu , Choudhry Mashkoor A. , Szalay Laszlo , Rue Loring W. , Bland Kirby I. , Chaudry Irshad H.
Published: May 2004

Recent studies have shown that dehydroepiandrosterone (DHEA) administration after trauma-hemorrhage (T-H) improves cardiovascular function and decreases cytokine production in male animals. Although androstenediol, one of the metabolites of DHEA, is reported to have estrogen-like activity, it remains unknown whether androstenediol per se has any salutary effects on cytokines and cardiovascular function after T-H. To examine this effect, male Sprague-Dawley rats underwent laparotomy and were bled to and maintained at a mean arterial blood pressure of 35–40 mmHg for ∼90 min. The animals were resuscitated with four times the volume of maximal bleedout volume in the form of Ringer lactate. Androstenediol (1 mg/kg body wt iv) or vehicle was administered at the end of resuscitation. Twenty-four hours after resuscitation, cardiac function and organ blood flow were measured by using 85Sr-microspheres. Circulating levels of nitrate/nitrite and IL-6 were also determined. Cardiovascular function and organ blood flow were significantly depressed after T-H. However, these parameters were restored by androstenediol treatment. The elevated plasma IL-6 levels after T-H were also lowered by androstenediol treatment. In contrast, plasma levels of nitrate/nitrite were the highest in the androstenediol-treated T-H animals. Because androstenediol administration after T-H decreases cytokine production and improves cardiovascular function, this agent appears to be a novel and useful adjunct for restoring the depressed cardiovascular function and for cytokine production in males after adverse circulatory conditions.
Apolipoprotein A-IV stimulates duodenal vagal afferent activity to inhibit gastric motility via a CCK1 pathway
Authors: Glatzle J. , Darcel N. , Rechs A. J. , Kalogeris T. J. , Tso P. , Raybould H. E.
Published: May 2004

Apolipoprotein A-IV (apo A-IV), a peptide expressed by enterocytes in the mammalian small intestine and released in response to long-chain triglyceride absorption, may be involved in the regulation of gastric acid secretion and gastric motility. The specific aim of the present study was to determine the pathway involved in mediating inhibition of gastric motility produced by apo A-IV. Gastric motility was measured manometrically in response to injections of either recombinant purified apo A-IV (200 μg) or apo A-I, the structurally similar intestinal apolipoprotein not regulated by triglyceride absorption, close to the upper gastrointestinal tract in urethane-anesthetized rats. Injection of apo A-IV significantly inhibited gastric motility compared with apo A-I or vehicle injections. The response to exogenous apo A-IV injections was significantly reduced by 77 and 55%, respectively, in rats treated with the CCK1 receptor blocker devazepide or after functional vagal deafferentation by perineural capsaicin treatment. In electrophysiological experiments, isolated proximal duodenal vagal afferent fibers were recorded in vitro in response to close-arterial injection of vehicle, apo A-IV (200 μg), or CCK (10 pmol). Apo A-IV stimulated the discharge of duodenal vagal afferent fibers, significantly increasing the discharge in 4/7 CCK-responsive units, and the response was abolished by CCK1 receptor blockade with devazepide. These data suggest that apo A-IV released from the intestinal mucosa during lipid absorption stimulates the release of endogenous CCK that activates CCK1 receptors on vagal afferent nerve terminals initiating feedback inhibition of gastric motility.
Role of the calcium-sensing receptor in parathyroid gland physiology
Authors: Chen Randolph A. , Goodman William G.
Published: May 2004

The calcium-sensing receptor (CaSR) represents the molecular mechanism by which parathyroid cells detect changes in blood ionized calcium concentration and modulate parathyroid hormone (PTH) secretion to maintain serum calcium levels within a narrow physiological range. Much has been learned in recent years about the diversity of signal transduction through the CaSR and the various factors that affect receptor expression. Beyond its classic role as a determinant of calcium-regulated PTH secretion, signaling through the CaSR also influences both gene transcription and cell proliferation in parathyroid cells. The CaSR thus serves a broad physiological role by integrating several distinct aspects of parathyroid gland function. The current review summarizes recent developments that enhance our understanding of the CaSR and its fundamental importance in parathyroid gland physiology.
Regulation of calcium signaling by polycystin-2
Authors: Cantiello Horacio F.
Published: May 2004

Autosomal dominant PKD (ADPKD) is a common lethal genetic disorder characterized by progressive development of fluid-filled cysts in the kidney and other target organs. ADPKD is caused by mutations in the PKD1 and PKD2 genes, encoding the transmembrane proteins polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Although the function and putative interacting ligands of PC1 are largely unknown, recent evidence indicates that PC2 behaves as a TRP-type Ca2+-permeable nonselective cation channel. The PC2 channel is implicated in the transient increase in cytosolic Ca2+in renal epithelial cells and may be linked to the activation of subsequent signaling pathways. Recent studies also indicate that PC1 functionally interacts with PC2 such that the PC1-PC2 channel complex is an obligatory novel signaling pathway implicated in the transduction of environmental signals into cellular events. The present review purposely avoids issues of regulation of PC2 expression and trafficking and focuses instead on the evidence for the TRP-type cation channel function of PC2. How its role as a cation channel may unmask mechanisms that trigger Ca2+transport and regulation is the focus of attention. PC2 channel function may be essential in renal cell function and kidney development. Nonrenal-targeted expression of PC2 and related proteins, including the cardiovascular system, also suggests previously unforeseeable roles in signal transduction.
Early release of neonatal ureteral obstruction preserves renal function
Authors: Shi Yimin , Pedersen Michael , Li Chunling , Wen Jian Guo , Thomsen Klaus , Stødkilde-Jørgensen Hans , Jørgensen Troels Munch , Knepper Mark A. , Nielsen Søren , Djurhuus Jens Christian , Frøkiær Jørgen
Published: May 2004

The incidence of congenital hydronephrosis is ∼1% and is often associated with renal insufficiency. It is unknown whether early release is essential to prevent deterioration of renal function. Rats were subjected to partial unilateral ureteral obstruction (PUUO) on postnatal day 2. The obstruction was left in place or released after 1 or 4 wk. Renal blood flow (RBF) and kidney size were measured sequentially over 24 wk using MRI. In rats in which the obstruction was left in place, RBF of the obstructed kidney was progressively reduced to 0.92 ± 0.17 vs. 1.79 ± 0.12 ml·min−1·100 g body wt−1( P < 0.05) after 24 wk. Similarly, glomerular filtration rate of the obstructed kidney was severely reduced at 24 wk: 172 ± 36 vs. 306 ± 42 μl·min−1·100 g body wt−1( P < 0.05). These changes were preceded by development of severe hydronephrosis and obstructive nephropathy with a reduction in total protein content: 45 ± 3 vs. 58 ± 4 mg/kidney. Moreover, nonreleased PUUO caused a marked natriuresis (0.32 ± 0.07 vs. 0.11 ± 0.02 μmol·min−1·100 g body wt−1, P < 0.05) and impaired solute free water reabsorption (0.47 ± 0.16 vs. 2.71 ± 0.67 μl·min−1·100 g body wt−1, P < 0.05), consistent with a significant downregulation of Na-K-ATPase to 62 ± 7%, aquaporin-1 to 53 ± 3%, and aquaporin-3 to 53 ± 7% of sham levels. Release after 1 wk completely prevented development of hydronephrosis, reduction in RBF and glomerular filtration rate, and downregulation of renal transport proteins, whereas release after 4 wk had no effect. These results suggest that early release of neonatal obstruction provides dramatically better protection of renal function than release of obstruction after the maturation process is completed.
Acatalasemia sensitizes renal tubular epithelial cells to apoptosis and exacerbates renal fibrosis after unilateral ureteral obstruction
Authors: Sunami Reiko , Sugiyama Hitoshi , Wang Da-Hong , Kobayashi Mizuho , Maeshima Yohei , Yamasaki Yasushi , Masuoka Noriyoshi , Ogawa Norio , Kira Shohei , Makino Hirofumi
Published: May 2004

Tissue homeostasis is determined by the balance between oxidants and antioxidants. Catalase is an important antioxidant enzyme regulating the level of intracellular hydrogen peroxide and hydroxyl radicals. The effect of catalase deficiency on renal tubulointerstitial injury induced by unilateral ureteral obstruction (UUO) has been studied in homozygous acatalasemic mutant mice (C3H/AnLCsbCsb) compared with wild-type mice (C3H/AnLCsaCsa). Complete UUO caused interstitial cell infiltration, tubular dilation and atrophy, and interstitial fibrosis with accumulation of type IV collagen in obstructed kidneys (OBK) of both mouse groups. However, the degree of injury showed a significant increase in OBK of acatalasemic mice compared with that of wild-type mice until day 7. The deposition of lipid peroxidation products including 4-hydroxy-2-hexenal, malondialdehyde, and 4-hydroxy-2-nonenal was severer in dilated tubules of acatalasemic OBK. Apoptosis in tubular epithelial cells significantly increased in acatalasemic OBK at day 4. Expression of caspase-9, a marker of mitochondrial pathway-derived apoptosis, increased in dilated tubules of acatalasemic mice. The level of catalase activity remained low in acatalasemic OBK until day 7 without compensatory upregulation of glutathione peroxidase activity. The data indicate that acatalasemia exacerbated oxidation of renal tissue and sensitized tubular epithelial cells to apoptosis in OBK of UUO. This study demonstrates that catalase deficiency enhanced tubulointerstitial injury and fibrosis in a murine model of UUO and thus supports the protective role of catalase in this model.
Macula densa basolateral ATP release is regulated by luminal [NaCl] and dietary salt intake
Authors: Komlosi Peter , Peti-Peterdi Janos , Fuson Amanda L. , Fintha Attila , Rosivall Laszlo , Bell Phillip Darwin
Published: May 2004

One component of the macula densa (MD) tubuloglomerular feedback (TGF) signaling pathway may involve basolateral release of ATP through a maxi-anion channel. Release of ATP has previously been studied during a maximal luminal NaCl concentration ([NaCl]L) stimulus (20–150 mmol/l). Whether MD ATP release occurs during changes in [NaCl]Lwithin the physiological range (20–60 mmol/l) has not been examined. Also, because TGF is known to be enhanced by low dietary salt intake, we examined the pattern of MD ATP release from salt-restricted rabbits. Fluorescence microscopy, with fura 2-loaded cultured mouse mesangial cells as biosensors, was used to assess ATP release from the isolated, perfused thick ascending limb containing the MD segment. The mesangial biosensor cells, which contain purinergic receptors and elevate intracellular Ca2+concentration ([Ca2+]i) on ATP binding, were placed adjacent to the MD basolateral membrane. Elevations in [NaCl]Lbetween 0 and 80 mmol/l, in 20-mmol/l increments, caused stepwise increases in [Ca2+]i, with the highest increase at [NaCl]Lof ∼60 mmol/l. Luminal furosemide at 10−4mol/l blocked ATP release, which suggests that the efflux of ATP required MD Na-2Cl-K cotransport. A low-salt diet for 1 wk increased the magnitude of [NaCl]L-dependent elevations in biosensor [Ca2+]iby twofold, whereas high-salt intake had no effect. In summary, ATP release occurs over the same range of [NaCl]L(20–60 mmol/l) previously reported for TGF responses, and, similar to TGF, ATP release was enhanced by dietary salt restriction. Thus these two findings are consistent with the role of MD ATP release as a signaling component of the TGF pathway.
High glucose concentration stimulates intracellular renin activity and angiotensin II generation in rat mesangial cells
Authors: Vidotti D. B. , Casarini D. E. , Cristovam P. C. , Leite C. A. , Schor N. , Boim M. A.
Published: May 2004

Increased intrarenal renin-angiotensin system activity contributes to diabetic nephropathy. ANG II generation in mesangial cells (MC) is increased by high-glucose (HG) exposure. This study assessed the mechanisms involved in the glucose-induced ANG II generation in rat MC. Under basal conditions, MC mainly secreted prorenin. HG decreased prorenin secretion and induced a striking 30-fold increase in intracellular renin activity. After 72 h of HG exposure, only the mRNA levels for angiotensinogen and angiotensin-converting enzyme (ACE) were significantly elevated. However, after shorter periods of 24 h of HG stimulation the mRNA levels of the enzymes prorenin and cathepsin B, besides that for ACE, were significantly increased. The results suggest that the HG-induced increase in ANG II generation in MC results from an increase in intracellular renin activity mediated by at least three factors: a time-dependent stimulation of (pro)renin gene transcription, a reduction in prorenin enzyme secretion, and an increased rate of conversion of prorenin to active renin, probably mediated by cathepsin B. The increase in angiotensinogen mRNA in parallel to increased renin activity indicates that HG also increased the availability of the renin substrate. The consistent upregulation of ACE mRNA suggests that, besides renin, ACE is directly involved in the increased mesangial ANG II generation induced by HG.
AE2 isoforms in rat kidney: immunohistochemical localization and regulation in response to chronic NH4Cl loading
Authors: Frische Sebastian , Zolotarev Alexander S. , Kim Young-Hee , Praetorius Jeppe , Alper Seth , Nielsen Søren , Wall Susan M.
Published: May 2004

Three splice variants of anion exchanger (AE)2 (AE2a, b, and c) have been described in the rat, but their relative distribution in rat kidney is not known. The purpose of this study was to describe the segmental and cellular distribution of the AE2 isoforms in the rat kidney and to evaluate whether the expression levels of these AE2 isoforms are regulated independently in response to chronic NH4Cl loading. Two polyclonal antibodies were generated, respectively, recognizing a NH2-terminal peptide unique to AE2a and an amino acid sequence common to AE2a and AE2b. Antibody specificities were tested using cells transfected separately with the AE2a, AE2b, and AE2c isoforms. Immunohistochemistry on sections of paraffin-embedded rat kidneys showed a distribution of AE2a/AE2b labeling in the kidney similar to the distribution of AE2 in the rat kidney reported previously. AE2 is highly expressed in the medullary thick ascending limb, cortical thick ascending limb (cTAL), and macula densa. The pattern of AE2a-specific labeling differed from the pattern of AE2a/AE2b labeling in that relatively more of the total immunolabel was observed in the terminal inner medullary collecting duct. NH4Cl loading (0.033 mmol NH4Cl/g body wt for 7 days) did not change the labeling of AE2 isoforms in the medulla, whereas the labeling in the cortex was intensified and included more distal parts of the cTAL. Immunoblotting confirmed upregulation of AE2a/b expression in the cortex. These results indicate that AE2a and AE2b are differentially expressed and regulated in the rat kidney. The regulation following NH4Cl loading of AE2b in the cTAL suggests a role for AE2 in transepithelial bicarbonate reabsorption in this segment.
Probing the impact of axial diffusion on nitric oxide exchange dynamics with heliox
Authors: Shin Hye-Won , Condorelli Peter , Rose-Gottron Christine M. , Cooper Dan M. , George Steven C.
Published: May 2004

Exhaled nitric oxide (NO) is a potential noninvasive index of lung inflammation and is thought to arise from the alveolar and airway regions of the lungs. A two-compartment model has been used to describe NO exchange; however, the model neglects axial diffusion of NO in the gas phase, and recent theoretical studies suggest that this may introduce significant error. We used heliox (80% helium, 20% oxygen) as the insufflating gas to probe the impact of axial diffusion (molecular diffusivity of NO is increased 2.3-fold relative to air) in healthy adults (21–38 yr old, n = 9). Heliox decreased the plateau concentration of exhaled NO by 45% (exhalation flow rate of 50 ml/s). In addition, the total mass of NO exhaled in phase I and II after a 20-s breath hold was reduced by 36%. A single-path trumpet model that considers axial diffusion predicts a 50% increase in the maximum airway flux of NO and a near-zero alveolar concentration (CaNO) and source. Furthermore, when NO elimination is plotted vs. constant exhalation flow rate (range 50–500 ml/s), the slope has been previously interpreted as a nonzero CaNO (range 1–5 ppb); however, the trumpet model predicts a positive slope of 0.4–2.1 ppb despite a zero CaNO because of a diminishing impact of axial diffusion as flow rate increases. We conclude that axial diffusion leads to a significant backdiffusion of NO from the airways to the alveolar region that significantly impacts the partitioning of airway and alveolar contributions to exhaled NO.
fMRI-Adaptation Reveals Dissociable Neural Representations of Identity and Expression in Face Perception
Authors: Winston J. S. , Henson R.N.A. , Fine-Goulden M. R. , Dolan R. J.
Published: May 2004

The distributed model of face processing proposes an anatomical dissociation between brain regions that encode invariant aspects of faces, such as identity, and those that encode changeable aspects of faces, such as expression. We tested for a neuroanatomical dissociation for identity and expression in face perception using a functional MRI (fMRI) adaptation paradigm. Repeating identity across face pairs led to reduced fMRI signal in fusiform cortex and posterior superior temporal sulcus (STS), whereas repeating emotional expression across pairs led to reduced signal in a more anterior region of STS. These results provide neuroanatomical evidence for the distributed model of face processing and highlight a dissociation within right STS between a caudal segment coding identity and a more rostral region coding emotional expression.
Do Children With Focal Cerebellar Lesions Show Deficits in Shifting Attention?
Authors: Schoch B. , Gorissen B. , Richter S. , Ozimek A. , Kaiser O. , Dimitrova A. , Regel J.P. , Wieland R. , Hövel M. , Gizewski E. , Timmann D.
Published: May 2004

More recent findings suggest a possible role of the cerebellum in nonmotor functions. Disability of individuals with cerebellar damage in rapidly shifting attention is one frequently used example to support cerebellar involvement in mental skills. The original proposal was based on findings in five children with chronic surgical lesions of the cerebellum and a young adult with a degenerative disorder. The aim of the present study was to repeat Akshoomoff and Courchesne's initial findings in a larger group of children with focal cerebellar lesions. Ten children with cerebellar lesions and 10 age- and sex-matched controls were tested. Neocerebellar areas were affected in all children with cerebellar damage except one based on detailed analysis of MRI scans. Subjects had to perform a focus and a shift attention task. Two visual and two auditory stimuli were presented in a pseudorandom order. An ellipse and a high-pitched tone were presented less frequently than a circle and a low-pitched tone. Rare stimuli were presented at five different time intervals. In the focus tasks, subjects had to react to the same rare stimulus of one of the two modalities. In the shift task, subjects had to switch between the two rare stimuli. Motor deficits based on reaction times were small in cerebellar children compared with controls. The ability of target detection did not significantly differ in the children with cerebellar lesions compared with the control children in both the focus and the shift attention task. In particular, children with cerebellar damage showed no significant impairment in rapid (<2 s) shifts of attention. The present findings indicate that the cerebellum may be less critical in attention related processes than suggested previously.
Shared and Private Variability in the Auditory Cortex
Authors: Deweese Michael R. , Zador Anthony M.
Published: May 2004

The high variability of cortical sensory responses is often assumed to impose a major constraint on efficient computation. In the auditory cortex, however, response variability can be very low. We have used in vivo whole cell patch-clamp methods to study the trial-to-trial variability of the subthreshold fluctuations in membrane potential underlying tone-evoked responses in the auditory cortex of anesthetized rats. Using methods adapted from classical quantal analysis, we partitioned this subthreshold variability into a private component (which includes synaptic, thermal, and other sources local to the recorded cell) and a shared component arising from network interactions. Here we report that this private component is remarkably small, usually about 1–3 mV, as quantified by the variance divided by the mean of the ensemble of tone-evoked response heights. The shared component can be much larger, and shows more heterogeneity across the population, ranging from about 0 to 10 mV. The remarkable fact that, at least 5 synapses from the auditory periphery, this variability remains so small raises the possibility that the intervening neural circuitry is organized so as to prevent private noise from accumulating as neural signals propagate to the cortex.
Properties of Quantal Transmission at CA1 Synapses
Authors: Raghavachari Sridhar , Lisman John E.
Published: May 2004

We have used Monte Carlo simulations to understand the generation of quantal responses at the single active zones of CA1 synapses. We constructed a model of AMPA channel activation that accounts for the responses to controlled glutamate application and a model of glutamate diffusion in the synaptic cleft. With no further adjustments to these models, we simulated the response to the release of glutamate from a single vesicle. The predicted response closely matches the rise time of observed responses, which recent measurements show is much faster (<100 μs) than previously thought. The simulations show that initial channel opening is driven by a brief (<100 μs) glutamate spike near the site of vesicle fusion, producing a hotspot of channel activation (diameter: ∼250 nm) smaller than many synapses. Quantal size therefore depends more strongly on the density of channels than their number, a finding that has important implications for measuring synaptic strength. Recent measurements allow estimation of AMPA receptor density at CA1 synapses. Using this value, our simulations correctly predicts a quantal amplitude of ∼10 pA. We have also analyzed the properties of excitatory postsynaptic currents (EPSCs) generated by the multivesicular release that can occur during evoked responses. We find that summation is nearly linear and that the existence of multiple narrow peaks in amplitude histograms can be accounted for. It has been unclear how to reconcile the existence of these narrow peaks, which indicate that the variation of quantal amplitude is small (CV < 0.2) with the highly variable amplitude of miniature EPSCs (mEPSCs; CV ∼ 0.6). According to one theory, mEPSC variability arises from variation in vesicle glutamate content. However, both our modeling results and recent experimental results indicate that this view cannot account for the observed rise time/amplitude correlation of mEPSCs. In contrast, this correlation and the high mEPSC variability can be accounted for if some mEPSCs are generated by two or more vesicles released with small temporal jitter. We conclude that a broad range of results can be accounted for by simple principles: quantal amplitude (∼10 pA) is stereotyped, some mEPSCs are multivesicular at moderate and large synapses, and evoked responses are generated by quasi-linear summation of multiple quanta.
Expression profiling analysis of the metabolic and inflammatory changes following burn injury in rats
Authors: Vemula M. , Berthiaume F. , Jayaraman A. , Yarmush M. L.
Published: May 2004

Burn injury initiates an inflammatory response as part of the healing process that is associated with extensive metabolic adjustments. While most studies have focused on understanding these changes from a biochemical perspective, not much work has been done to characterize these processes at the gene expression level. As a first step, we have comprehensively analyzed changes in gene expression in rat livers during the first 24 h after burn injury using Affymetrix GeneChips, which showed 339 genes to be differentially expressed at a statistical significance of P < 0.05 and changed at least twofold. Functional classification based on gene ontology terms indicated that two categories, metabolism (28%) and inflammation (14%), accounted for nearly 42%. Detailed analysis of the metabolism group of genes indicated that fatty acid (FA) and triglyceride (TG) biosynthesis in the liver were unchanged, whereas TG utilization, FA import, and β-oxidation increased after burn injury. The increased FA pools after burn injury appear to serve as substrates for ATP production. Following burn injury, the cholesterol biosynthetic pathway was suppressed while cholesterol was increasingly imported and converted into bile acids. The inflammatory genes that were altered included several classic acute phase response markers, as well as genes involved in the complement, kinin, clotting, and fibrinolytic protein systems. These temporally coordinated changes in gene expression were also corroborated by biochemical measurements for FA, TG, cholesterol, and ATP. Together, these data indicate that FA are increasingly imported and oxidized in the liver to meet the enhanced energy demands arising from an inflammatory response during the first 24 h after burn injury.
‘The Multiple-Sit-to-Stand’ Field Test for Older Adults: What Does It Measure?
Authors: Netz Yael , Ayalon Moshe , Dunsky Ayelet , Alexander Neil
Published: May 2004

Background: The need to predict decline in functional status in a large number of older adults has brought researchers and clinicians to develop easy-to-administer field tests. One of them is the ‘multiple-sit-to-stand’ (MSTS), which claims to measure leg strength. Objective: To assess the extent to which the MSTS is a leg strength, leg endurance or general endurance test. Methods: 49 independently functioning women (72.2 ± 6.4 years) were assessed on the MSTS, on a submaximal stress test, and on strength and endurance of knee extensors measured by isokinetics. The knee extensors were selected, more than in other muscle groups responsible for movement of the lower extremity, as the largest range of motion, and the largest torques required while performing activities of daily living (ADL) is found in this group. Results: The correlation of the MSTS with the stress test was moderate and significant but very low and nonsignificant with the isokinetic measurements. Conclusions: The MTST is not able to predict strength of knee extensors, the leading group of leg muscles in ADL. If at all, it predicts general endurance rather than any measure – muscle strength or muscle endurance – of lower extremities. Longitudinal studies assessing the potential of the MSTS to predict deterioration in ADL in older adults are recommended, as well as studies assessing other factors related to both MSTS and ADL, such as muscle-nerve coordination affecting multiple joint activities.
Age-Dependent Expression of Advanced Glycation End Product Receptor Genes in the Human Heart
Authors: Casselmann C. , Reimann A. , Friedrich I. , Schubert A. , Silber R.-E. , Simm A.
Published: May 2004

Background: Advanced glycation end products (AGEs) are formed by the reaction of sugars and NH2 groups of lysine and arginine residues and have been shown to accumulate in tissues, including the heart, with normal ageing. The interaction of AGEs with their receptors is known to cause changes in cell function, leading, for example, to the production of pro-inflammatory cytokines and free radicals. Objective: This study investigated the gene expression of the five known AGE receptors: AGE-R1, AGE-R2, AGE-R3, the scavenger receptor II, and the receptor for AGEs (RAGE) in human heart tissue. Methods: Tissue samples were taken from the right cardiac auricles from three patient groups: children (2.4 ± 1.1 years), adults (45.3 ± 0.8 years) and elderly subjects (76.4 ± 0.4 years). Analysis of gene expression of the five AGE receptors was performed using the reverse transcription-polymerase chain reaction (RT-PCR) and 18S mRNA levels as loading controls. Results: Our results show an age-dependent upregulation of the genes for AGE-R3 and the scavenger receptor II, but a downregulation for RAGE and no significant differences for AGE-R1 and AGE-R2. Conclusion: This study supports a pathophysiological function for AGE receptors such as AGE-R3 and RAGE in the ageing heart.
Physical Function and Health Status among Seniors with and without a Fear of Falling
Authors: Brouwer Brenda , Musselman Kristin , Culham Elsie
Published: May 2004

Background: Fear of falling (FF) is pervasive among older people and is an independent risk factor for decreased mobility and loss of quality of life. Although it is a serious health concern, little is known about the severity of the physical and health-related deficits in high-functioning fearful seniors. Objective: This study examined the physical correlates of FF in community-dwelling seniors in relation to their non-fearful counterparts and also explored the relevance of recent fall history. Subjects: Twenty-five volunteers who stated that they had curtailed their activities due to a FF and who reported themselves to be healthy participated. Non-fearful, age- and gender-matched subjects were also recruited and served as a comparison group. Methods: This cross-sectional study had participants come to the laboratory on one occasion for about 1.5 h. Limits of balance stability, walking speed, and lower limb muscle strength were measured in random order. In addition, the SF-36, the Activities-specific Balance Confidence (ABC) scale and the Human Activity Profile questionnaires were completed to provide measures of heath status, FF and activity levels, respectively. Results: Subjects with a FF had lower ABC scores (69.8 ± 10.2) than controls (90.2 ± 7.9; p < 0.001), and although they reported activity curtailment, the groups presented similar activity profiles (p > 0.05). Balance ability was not compromised in seniors with a FF, although their walking speed was slower than that of control subjects (p < 0.004). Lower limb weakness was significant in the FF group, which also reported low physical health. Perceived physical health, activity and hip flexor torque in combination accounted for almost 62% of the variance in ABC scores. Secondary analysis of the data from the FF group revealed a tendency for those who had fallen in the past year to restrict their limits of stability compared to those who had not fallen; though generally the effect sizes were small to moderate. Conclusions: The marked deficits in strength and health status found among seniors living independently in the community, who are in good health, but report being fearful of falling underscores the seriousness of FF as a potential health risk factor in the well elderly.
Memory Impairment Means Less Pain for Mice
Authors: Pickering Gisèle , Chapuy Eric , Eschalier Alain , Dubray Claude
Published: May 2004

Background: Clinical observations have reported that individuals with memory deterioration, like in Alzheimer’s disease, display a lesser pain sensibility than patients with no cognitive impairment. Objective: To clarify the link between pain and loss of memory, we studied how memory-impaired mice behave when submitted to hotplate nociceptive tests. Methods: For 5 days (D1–D5), male CD1 mice were injected daily intraperitonealy with saline or scopolamine (s, an anticholinergic drug, 0.2 mg/kg) or ketamine (k, an N-methyl-D-aspartate receptor antagonist (NMDAr), 2.5 mg/kg), at doses leading to memory impairment with no analgesic effect. From D6 to D9, all received saline only. They were placed on the hotplate and removed at the first sign of discomfort, response time being recorded. Results: From D1 to D5, reaction time decreased significantly in controls only and did not change in mice with scopolamine or ketamine. From D6 to D9, response times decreased (p < 0.05 (s) and p < 0.0001 (k)) to reach the steady state of control animals. At D5, response time was significantly prolonged for scopolamine (p < 0.01) and ketamine (p < 0.05), compared to controls. Conclusion: These results show that pain sensibility needs the integrity of the central cholinergic and of the NMDA systems, and that mice with memory impairment display a lesser pain sensibility than normal mice. Further research on the complex interactions of receptors and neurotransmitters involved in pain and cognition could assist in gaining a better understanding of pain and analgesia in patients with memory impairment and in demented individuals.