bluuebunny/crossref_metadata_2025 huggingface dataset:
SHARP POINTWISE BOUNDS FOR PERTURBED VISCOUS SHOCK WAVES
Authors: HOWARD PETER , RAOOFI MOHAMMADREZA , ZUMBRUN KEVIN
Published: May 2006

Refining previous work of Zumbrun, Mascia–Zumbrun, Raoofi, Howard–Zumbrun and Howard–Raoofi, we derive sharp pointwise bounds on behavior of perturbed viscous shock profiles for large-amplitude Lax or overcompressive type shocks and physical viscosity. These extend well-known results of Liu obtained by somewhat different techniques for small-amplitude Lax type shocks and artificial viscosity, completing a program initiated by Zumbrun and Howard. As pointed out by Liu, the key to obtaining sharp bounds is to take account of cancellation associated with the property that the solution decays faster along characteristic than in other directions. Thus, we must here estimate characteristic derivatives for the entire nonlinear perturbation, rather than judicially chosen parts as in the work of Raoofi and Howard–Raoofi, a requirement that greatly complicates the analysis.
HOW INFLATION IS USED TO RESOLVE THE FLATNESS PROBLEM
Authors: SMOLLER JOEL , TEMPLE BLAKE
Published: May 2006

We give a mathematically rigorous exposition of the flatness problem, and show how Guth's original model of inflation is used to resolve it.
Pizza and pasta help students learn metabolism
Authors: Passos Renato M. , Sé Alexandre B. , Wolff Vanessa L. , Nobrega Yanna K. M. , Hermes-Lima Marcelo
Published: May 2006

In this article, we report on an experiment designed to improve the learning of metabolic biochemistry by nutrition and medical undergraduate students. Twelve students participated in a monitored lunch and had their blood extracted for analysis 1) before lunch, 2) 30 min after lunch, and 3) 3 h after lunch. The subjects were divided in two groups. One group had a hyperglicidic meal [pasta plus orange juice: 80% carbohydrate, 10% protein, and 10% lipid (estimated values)] and the other group had a hyperlipidic meal (calabresi pizza plus diet soda: 36% carbohydrate, 18% protein, and 46% lipid). Individual quantities of food were based on body mass index, age, and sex. The blood parameters analyzed were glucose, triglycerides (TG), and urea. Glucose remained constant in the three measurements in both groups. The TG concentration in the pasta group was constant before and after lunch but increased significantly during the evening. In the pizza group, TG increased after lunch and remained constant in the evening. Levels of urea increased only in the evening, specially in the pizza group. These results were used for the final biochemistry exam. With the maximum score set as 10, the average score was 6.0 ± 2.4 ( n = 102). We considered this activity a unique way of evaluating important issues on metabolism, because students had several hours to work on the final exam (with free access to a bibliography). It was also a good didactic experience (problem-based learning like) for the subject students, because they had to work in all phases of the experiment (idealization, realization, and analysis) and participated actively in the elaboration and correction of the exam.
Bitter stimuli induce Ca2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca2+ channels
Authors: Chen Monica C. , Wu S. Vincent , Reeve Joseph R. , Rozengurt Enrique
Published: May 2006

We previously demonstrated the expression of bitter taste receptors of the type 2 family (T2R) and the α-subunits of the G protein gustducin (Gαgust) in the rodent gastrointestinal (GI) tract and in GI endocrine cells. In this study, we characterized mechanisms of Ca2+ fluxes induced by two distinct T2R ligands: denatonium benzoate (DB) and phenylthiocarbamide (PTC), in mouse enteroendocrine cell line STC-1. Both DB and PTC induced a marked increase in intracellular [Ca2+] ([Ca2+]i) in a dose- and time-dependent manner. Chelating extracellular Ca2+ with EGTA blocked the increase in [Ca2+]i induced by either DB or PTC but, in contrast, did not prevent the effect induced by bombesin. Thapsigargin blocked the transient increase in [Ca2+]i induced by bombesin, but did not attenuate the [Ca2+]i increase elicited by DB or PTC. These results indicate that Ca2+ influx mediates the increase in [Ca2+]i induced by DB and PTC in STC-1 cells. Preincubation with the L-type voltage-sensitive Ca2+ channel (L-type VSCC) blockers nitrendipine or diltiazem for 30 min inhibited the increase in [Ca2+]i elicited by DB or PTC. Furthermore, exposure to the L-type VSCCs opener BAY K 8644 potentiated the increase in [Ca2+]i induced by DB and PTC. Stimulation with DB also induced a marked increase in the release of cholecystokinin from STC-1 cells, an effect also abrogated by prior exposure to EGTA or L-type VSCC blockers. Collectively, our results demonstrate that bitter tastants increase [Ca2+]i and cholecystokinin release through Ca2+ influx mediated by the opening of L-type VSCCs in enteroendocrine STC-1 cells.
Calcium waves in intact guinea pig gallbladder smooth muscle cells
Authors: Balemba Onesmo B. , Heppner Thomas J. , Bonev Adrian D. , Nelson Mark T. , Mawe Gary M.
Published: May 2006

Intracellular Ca2+waves and spontaneous transient depolarizations were investigated in gallbladder smooth muscle (GBSM) whole mount preparations with intact mucosal layer [full thickness (FT)] by laser confocal imaging of intracellular Ca2+and voltage recordings with microelectrodes, respectively. Spontaneous Ca2+waves arose most often near the center, but sometimes from the extremities, of GBSM cells. They propagated regeneratively by Ca2+-induced Ca2+release involving inositol 1,4,5-trisphosphate [Ins( 1 , 4 , 5 )P3] receptors and were not affected by TTX and atropine (ATS). Spontaneous Ca2+waves and spontaneous transient depolarizations were more prevalent in FT than in isolated muscularis layer preparations and occurred with similar pattern in GBSM bundles. Ca2+waves were abolished by the Ins( 1 , 4 , 5 )P3receptor inhibitors 2-aminoethoxydiphenyl borate and xestospongin C and by caffeine and cyclopiazonic acid. These events were reduced by voltage-dependent calcium channels (VDCCs) inhibitors diltiazem and nifedipine, by PLC inhibitor U-73122, and by thapsigargin and ryanodine. ACh, CCK, and carbachol augmented Ca2+waves and induced Ca2+flashes. The actions of these agonists were inhibited by U-73122. These results indicate that in GBSM, discharge and propagation of Ca2+waves depend on sarco(endo)plasmic reticulum (SR) Ca2+release via Ins( 1 , 4 , 5 )P3receptors, PLC activity, Ca2+influx via VDCCs, and SR Ca2+concentration. Neurohormonal enhancement of GBSM excitability involves PLC-dependent augmentation and synchronization of SR Ca2+release via Ins( 1 , 4 , 5 )P3receptors. Ca2+waves likely reflect the activity of a fundamental unit of spontaneous activity and play an important role in the excitability of GBSM.
Distinct mechanisms of acid-induced HCO3−secretion in normal and slightly permeable stomachs
Authors: Aihara Eitaro , Sasaki Yoko , Ise Fumitaka , Kita Kazutomo , Nomura Yoko , Takeuchi Koji
Published: May 2006

We investigated the regulatory mechanism of acid-induced HCO3−secretion in the slightly permeable rat stomach after an exposure to hyperosmolar NaCl. Under urethane anesthesia, a rat stomach was mounted on a chamber and perfused with saline, and the secretion of HCO3−was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. Acidification of the normal stomach with 100 mM HCl increased HCO3−secretion, and this response was totally inhibited by pretreatment with indomethacin but not NG-nitro-l-arginine methyl ester (l-NAME) or chemical ablation of capsaicin-sensitive afferent neurons. Exposure of the stomach to 0.5 M NaCl deranged the unstirred mucus gel layer without damaging the surface epithelial cells. The stomach responded to 0.5 M NaCl by secreting slightly more HCO3−, in an indomethacin-inhibitable manner, and responded to even 10 mM HCl with a marked rise in HCO3−secretion, although 10 mM HCl did not have an effect in the normal stomach. The acid-induced HCO3−response in the NaCl-treated stomach was significantly but partially attenuated by indomethacin, l-NAME, or sensory deafferentation and was totally abolished when these treatments were combined. These results suggest that gastric HCO3−secretion in response to acid is regulated by two independent mechanisms, one mediated by prostaglandins (PGs) and the other by sensory neurons and nitric oxide (NO). The acid-induced HCO3−secretion in the normal stomach is totally mediated by endogenous PGs, but, when the stomach is made slightly permeable to acid, the response is markedly facilitated by sensory neurons and NO.
Evidence for epithelial-mesenchymal transitions in adult liver cells
Authors: Sicklick Jason K. , Choi Steve S. , Bustamante Marcia , McCall Shannon J. , Pérez Elizabeth Hernández , Huang Jiawen , Li Yin-Xiong , Rojkind Marcos , Diehl Anna Mae
Published: May 2006

Both myofibroblastic hepatic stellate cells (HSC) and hepatic epithelial progenitors accumulate in damaged livers. In some injured organs, the ability to distinguish between fibroblastic and epithelial cells is sometimes difficult because cells undergo epithelial-mesenchymal transitions (EMT). During EMT, cells coexpress epithelial and mesenchymal cell markers. To determine whether EMT occurs in adult liver cells, we analyzed the expression profile of primary HSC, two HSC lines, and hepatic epithelial progenitors. As expected, all HSC expressed HSC markers. Surprisingly, these markers were also expressed by epithelial progenitors. In addition, one HSC line expressed typical epithelial progenitor mRNAs, and these epithelial markers were inducible in the second HSC line. In normal and damaged livers, small ductular-type cells stained positive for an HSC marker. In conclusion, HSC and hepatic epithelial progenitors both coexpress epithelial and mesenchymal markers, providing evidence that EMT occurs in adult liver cells.
Bile acids stimulate PKCα autophosphorylation and activation: role in the attenuation of prostaglandin E1-induced cAMP production in human dermal fibroblasts
Authors: Le Man , Krilov Lada , Meng Jianping , Chapin-Kennedy Kelli , Ceryak Susan , Bouscarel Bernard
Published: May 2006

The aim was to identify the specific PKC isoform(s) and their mechanism of activation responsible for the modulation of cAMP production by bile acids in human dermal fibroblasts. Stimulation of fibroblasts with 25–100 μM of chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) led to YFP-PKCα and YFP-PKCδ translocation in 30–60 min followed by a transient 24- to 48-h downregulation of the total PKCα, PKCδ, and PKCε protein expression by 30–50%, without affecting that of PKCζ. Increased plasma membrane translocation of PKCα was associated with an increased PKCα phosphorylation, whereas increased PKCδ translocation to the perinuclear domain was associated with an increased accumulation of phospho-PKCδ Thr505 and Tyr311 in the nucleus. The PKCα specificity on the attenuation of cAMP production by CDCA was demonstrated with PKC downregulation or inhibition, as well as PKC isoform dominant-negative mutants. Under these same conditions, neither phosphatidylinositol 3-kinase, p38 MAP kinase, p42/44 MAP kinase, nor PKA inhibitors had any significant effect on the CDCA-induced cAMP production attenuation. CDCA concentrations as low as 10 μM stimulated PKCα autophosphorylation in vitro. This bile acid effect required phosphatidylserine and was completely abolished by the presence of Gö6976. CDCA at concentrations less than 50 μM enhanced the PKCα activation induced by PMA, whereas greater CDCA concentrations reduced the PMA-induced PKCα activation. CDCA alone did not affect PKCα activity in vitro. In conclusion, although CDCA and UDCA activate different PKC isoforms, PKCα plays a major role in the bile acid-induced inhibition of cAMP synthesis in fibroblasts. This study emphasizes potential consequences of increased systemic bile acid concentrations and cellular bile acid accumulation in extrahepatic tissues during cholestatic liver diseases.
Spatial Frequency Content in Optical Mapping of Cardiac Cell Monolayers
Authors: Bien Harold , Entcheva Emilia
Published: May 2006

Fluorescence imaging using voltage-sensitive dyes is an important tool for studying electrical propagation in the heart. Yet, the low amplitude of the voltage-sensitive component in the fluorescence signal and high acquisition rates dictated by the rapid propagation of the excitation wave front make it difficult to achieve recordings with high signal-to-noise ratios. Although spatially and temporally filtering the acquired signals has become de facto one of the key elements of optical mapping, there is no consensus regarding their use. Here we characterize the spatiotemporal spectra of optically recorded action potentials and determine the distortion produced by conical filters of different sizes. On the basis of these findings, we formulate the criteria for rational selection of filter characteristics. We studied the evolution of the spatial spectra of the propagating wave front after epicardial point stimulation of the isolated, perfused right ventricular free wall of the pig heart stained with di-4-ANEPPS. We found that short-wavelength (<3 mm) spectral components represent primarily noise and surface features of the preparation (coronary vessels, fat, and connective tissue). The time domain of the optical action potential spectrum also lacks high-frequency components (>100 Hz). Both findings are consistent with the reported effect of intrinsic blurring caused by light scattering inside the myocardial wall. The absence of high-frequency spectral components allows the use of aggressive low-pass spatial and temporal filters without affecting the optical action potential morphology. We show examples where the signal-to-noise ratio increased up to 150 with <3% distortion. A generalization of our approach to the rational filter selection in various applications is discussed.
Progression of coronary and mesenteric vascular dysfunction in Zucker obese and Zucker diabetic fatty rats
Authors: Oltman Christine L. , Richou Laura L. , Davidson Eric P. , Coppey Lawrence J. , Lund Donald D. , Yorek Mark A.
Published: May 2006

We investigated the progression of vascular dysfunction associated with the metabolic syndrome with and without hyperglycemia in lean, Zucker obese, and Zucker diabetic fatty (ZDF) rats. Responses of aorta and small coronary and mesenteric arteries were measured to endothelium-dependent and -independent vasodilators. Indices of oxidative stress were increased in serum from ZDF rats throughout the study, whereas values were increased in Zucker obese rats later in the study [thiobarbituric acid reactive substances: 0.45 ± 0.02, 0.59 ± 0.03 ( P < 0.05), and 0.58 ± 0.03 ( P < 0.05) μg/ml in serum from 28- to 40-wk-old lean, Zucker obese, and ZDF rats, respectively]. Acetylcholine (ACh)-induced relaxation was not altered in vessels from lean animals from 8–40 wk. ACh-induced relaxation was nearly abolished in coronary arteries from 28- to 36-wk-old Zucker obese rats and by 16–36 wk in ZDF rats and was attenuated in aorta and mesenteric vessels from ZDF rats [%relaxation to 10 μM ACh: 72.2 ± 7.1, 17.9 ± 5.9 ( P < 0.05), and 23.0 ± 4.5 ( P < 0.05) in coronary vessels; and 67.9 ± 9.2, 50.1 ± 5.5, and 42.3 ± 4.7 ( P < 0.05) in mesenteric vessels from 28- to 40-wk-old lean, Zucker obese, and ZDF rats, respectively]. The attenuated ACh-induced relaxation was improved when vessels were incubated with tiron, suggesting superoxide as a mechanism of endothelial dysfunction. Sodium nitroprusside-induced relaxation was not altered in aorta or coronary arteries and was potentiated in mesenteric arteries from Zucker obese rats. Our data suggest that diabetes enhances the progression of vascular dysfunction. Increases in indices of oxidative stress precede the development of dysfunction and may serve as a marker of endothelial damage.
Muscarinic regulation of neonatal rat bladder spontaneous contractions
Authors: Ng Yuen-Keng , de Groat William C. , Wu Hsi-Yang
Published: May 2006

In vitro preparations of whole urinary bladders of neonatal rats exhibit prominent myogenic spontaneous contractions, the amplitude and frequency of which can be increased by muscarinic agonists. The muscarinic receptor subtype responsible for this facilitation was examined in the present experiments. Basal spontaneous contractions in bladders from 1- to 2-wk-old Sprague-Dawley rats were not affected by M2 or M3 receptor antagonists. However, administration of 0.5 μM physostigmine, an anticholinesterase agent that increases the levels of endogenous acetylcholine, or 50–100 nM carbachol, a cholinergic agonist at low concentrations, which did not cause tonic contractions, significantly augmented the frequency and amplitude of spontaneous contractions. Blockade of M2 receptors with 0.1 μM AF-DX 116 or 1 μM methoctramine or blockade of M3 receptors with 50 nM 4-diphenylacetoxy- N-methylpiperidine methiodide or 0.1 μM 4-diphenylacetoxy- N-(2-chloroethyl)piperidine hydrochloride (4-DAMP mustard) reversed the physostigmine and carbachol responses. M2 and M3 receptor blockade did not alter the facilitation of spontaneous contractions induced by 10 nM BAY K 8644, an L-type Ca2+ channel opener, or 0.1 μM iberiotoxin, a large-conductance Ca2+-activated K+ channel blocker. NS-1619 (30 μM), a large-conductance Ca2+-activated K+ channel opener, decreased carbachol-augmented spontaneous contractions. These results suggest that spontaneous contractions in the neonatal rat bladder are enhanced by activation of M2 and M3 receptors by endogenous acetylcholine released in the presence of an anticholinesterase agent or a cholinergic receptor agonist.
Contractile properties of EDL and soleus muscles of myostatin-deficient mice
Authors: Mendias Christopher L. , Marcin James E. , Calerdon Daniel R. , Faulkner John A.
Published: May 2006

Myostatin is a negative regulator of muscle mass. The impact of myostatin deficiency on the contractile properties of healthy muscles has not been determined. We hypothesized that myostatin deficiency would increase the maximum tetanic force (Po), but decrease the specific Po(sPo) of muscles and increase the susceptibility to contraction-induced injury. The in vitro contractile properties of extensor digitorum longus (EDL) and soleus muscles from wild-type ( MSTN+/+), heterozygous-null ( MSTN+/−), and homozygous-null ( MSTN−/−) adult male mice were determined. For EDL muscles, the Poof both MSTN+/−and MSTN−/−mice were greater than the Poof MSTN+/+mice. For soleus muscles, the Poof MSTN−/−mice was greater than that of MSTN+/+mice. The sPoof EDL muscles of MSTN−/−mice was less than that of MSTN+/+mice. For soleus muscles, however, no difference in sPowas observed. Following two lengthening contractions, EDL muscles from MSTN−/−mice had a greater force deficit than that of MSTN+/+or MSTN+/−mice, whereas no differences were observed for the force deficits of soleus muscles. Myostatin-deficient EDL muscles had less hydroxyproline, and myostatin directly increased type I collagen mRNA expression and protein content. The difference in the response of EDL and soleus muscles to myostatin may arise from differences in the levels of a myostatin receptor, activin type IIB. Compared with the soleus, the amount of activin type IIB receptor was approximately twofold greater in EDL muscles. The results support a significant role for myostatin not only in the mass of muscles but also in the contractility and the composition of the extracellular matrix of muscles.
Effect of aging on the recovery following contraction-induced injury in muscles of female mice
Authors: Rader Erik P. , Faulkner John A.
Published: May 2006

By the age of 80 yr, the skeletal muscles of men and women decrease in mass and maximum force by ∼30%. Severe contraction-induced injury may contribute to these age-related declines. One to two months after a 225 lengthening contraction protocol (LCP), muscles of young/adult male mice recovered completely, whereas those of old male mice sustained deficits of ∼15% in mass and ∼25% in maximum force. Although gender-related differences in the early events of contraction-induced injury have been reported, the recovery phase of muscles in old female animals has not been investigated. The hypothesis tested was that 2 mo after a severe LCP to the plantar flexor muscle group, the magnitude of recovery of mass and force for old female mice is less than that for adult female mice. The LCP was administered to muscles of adult and old, female C57BL/6 mice. At 3 days, 1 mo, and 2 mo following the LCP, maximum isometric force was measured, and muscles were removed and weighed. Two months following the LCP, the muscles of adult female mice recovered mass and force. In contrast, for old female mice, even after 2 mo, muscle masses were decreased by 11% and maximum forces by 38%. We conclude that, as reported previously for old male mice, a severe contraction-induced injury to muscles of old female mice results in prolonged deficits in mass and force.
Chronic hypoxia augments uterine artery distensibility and alters the circumferential wall stress-strain relationship during pregnancy
Authors: Mateev Stephanie N. , Mouser Rhonda , Young David A. , Mecham Robert P. , Moore Lorna G.
Published: May 2006

Pregnancy-associated increases in uterine artery (UA) blood flow are due, in part, to vasoactive and growth-related changes that enlarge UA diameter. Although active and passive mechanical factors can contribute to this enlargement, their role is less well understood. We hypothesized that pregnancy increased UA distensibility and/or decreased myogenic tone. Given the fetal growth restriction and lower UA flow seen under chronic hypoxia, we further hypothesized that chronic hypoxia opposed these normal active and passive mechanical changes. UA were isolated from 12 nonpregnant and 12 pregnant (0.7 gestation) guinea pigs housed under normoxia or chronic hypoxia (3,960 m) and studied by pressure myography. Pregnancy increased UA diameter similarly under normoxia and hypoxia. Although chronic hypoxia raised resting tone in UA from nonpregnant guinea pigs to ∼20% and tone was greater in preconstricted pregnant chronically hypoxic vs. normoxic UA (both P < 0.01), there was an absence of myogenic response (i.e., an increase in tone with rising pressure) in all groups. Pregnancy increased UA distensibility 1.5-fold but did not change stiffness or the stress-strain relationship. Compared with vessels from normoxic pregnant animals, hypoxic pregnancy raised UA distensibility fourfold, decreased stiffness (rate constant b = 3.80 ± 1.06 vs. 8.92 ± 1.25, respectively, P < 0.01), lowered elastin by 50%, and shifted the stress-strain relationship upward such that four times as much strain was present at a given stress. We concluded that increased distensibility and low myogenic tone contribute to enlarging UA diameter and raising UA blood flow during pregnancy. Chronic hypoxia exaggerates the rise in distensibility and alters the stress-strain relationship in ways that may provoke vascular injury.
Signal Transmission Between Gap-Junctionally Coupled Passive Cables Is Most Effective at an Optimal Diameter
Authors: Nadim Farzan , Golowasch Jorge
Published: May 2006

We analyze simple morphological configurations that represent gap-junctional coupling between neuronal processes or between muscle fibers. Specifically, we use cable theory and simulations to examine the consequences of current flow from one cable to other gap-junctionally coupled passive cables. When the proximal end of the first cable is voltage clamped, the amplitude of the electrical signal in distal portions of the second cable depends on the cable diameter. However, this amplitude does not simply increase if cable diameter is increased, as expected from the larger length constant; instead, an optimal diameter exists. The optimal diameter arises because the dependency of voltage attenuation along the second cable on cable diameter follows two opposing rules. As cable diameter increases, the attenuation decreases because of a larger length constant yet increases because of a reduction in current density arising from the limiting effect of the gap junction on current flow into the second cable. The optimal diameter depends on the gap junction resistance and cable parameters. In branched cables, dependency on diameter is local and thus may serve to functionally compartmentalize branches that are coupled to other cells. Such compartmentalization may be important when periodic signals or action potentials cause the current flow across gap junctions.
Presynaptic GABABReceptors Regulate Retinohypothalamic Tract Synaptic Transmission by Inhibiting Voltage-Gated Ca2+Channels
Authors: Moldavan Mykhaylo G. , Irwin Robert P. , Allen Charles N.
Published: May 2006

Presynaptic GABABreceptor activation inhibits glutamate release from retinohypothalamic tract (RHT) terminals in the suprachiasmatic nucleus (SCN). Voltage-clamp whole cell recordings from rat SCN neurons and optical recordings of Ca2+-sensitive fluorescent probes within RHT terminals were used to examine GABAB-receptor modulation of RHT transmission. Baclofen inhibited evoked excitatory postsynaptic currents (EPSCs) in a concentration-dependent manner equally during the day and night. Blockers of N-, P/Q-, T-, and R-type voltage-dependent Ca2+channels, but not L-type, reduced the EPSC amplitude by 66, 36, 32, and 18% of control, respectively. Joint application of multiple Ca2+channel blockers inhibited the EPSCs less than that predicted, consistent with a model in which multiple Ca2+channels overlap in the regulation of transmitter release. Presynaptic inhibition of EPSCs by baclofen was occluded by ω-conotoxin GVIA (≤72%), mibefradil (≤52%), and ω-agatoxin TK (≤15%), but not by SNX-482 or nimodipine. Baclofen reduced both evoked presynaptic Ca2+influx and resting Ca2+concentration in RHT terminals. Tertiapin did not alter the evoked EPSC and baclofen-induced inhibition, indicating that baclofen does not inhibit glutamate release by activation of Kir3 channels. Neither Ba2+nor high extracellular K+modified the baclofen-induced inhibition. 4-Aminopyridine (4-AP) significantly increased the EPSC amplitude and the charge transfer, and dramatically reduced the baclofen effect. These data indicate that baclofen inhibits glutamate release from RHT terminals by blocking N-, T-, and P/Q-type Ca2+channels, and possibly by activation of 4-AP–sensitive K+channels, but not by inhibition of R- and L-type Ca2+channels or by Kir3 channel activation.
Sound Localization by Barn Owls in a Simulated Echoic Environment
Authors: Spitzer Matthew W. , Takahashi Terry T.
Published: May 2006

We examined the accuracy and precision with which the barn owl ( Tyto alba) turns its head toward sound sources under conditions that evoke the precedence effect (PE) in humans. Stimuli consisted of 25-ms noise bursts emitted from two sources, separated horizontally by 40°, and temporally by 3–50 ms. At delays from 3 to 10 ms, head turns were always directed at the leading source, and were nearly as accurate and precise as turns toward single sources, indicating that the leading source dominates perception. This lead dominance is particularly remarkable, first, because on some trials, the lagging source was significantly higher in amplitude than the lead, arising from the directionality of the owl's ears, and second, because the temporal overlap of the two sounds can degrade the binaural cues with which the owl localizes sounds. With increasing delays, the influence of the lagging source became apparent as the head saccades became increasingly biased toward the lagging source. Furthermore, on some of the trials at delays ≥20 ms, the owl turned its head, first, in the direction of one source, and then the other, suggesting that it was able to resolve two separately localizable sources. At all delays <50 ms, response latencies were longer for paired sources than for single sources. With the possible exception of response latency, these findings demonstrate that the owl exhibits precedence phenomena in sound localization similar to those in humans and cats, and provide a basis for comparison with neurophysiological data.
Adaptation in the Auditory Space Map of the Barn Owl
Authors: Gutfreund Yoram , Knudsen Eric I.
Published: May 2006

Auditory neurons in the owl’s external nucleus of the inferior colliculus (ICX) integrate information across frequency channels to create a map of auditory space. This study describes a powerful, sound-driven adaptation of unit responsiveness in the ICX and explores the implications of this adaptation for sensory processing. Adaptation in the ICX was analyzed by presenting lightly anesthetized owls with sequential pairs of dichotic noise bursts. Adaptation occurred in response even to weak, threshold-level sounds and remained strong for more than 100 ms after stimulus offset. Stimulation by one range of sound frequencies caused adaptation that generalized across the entire broad range of frequencies to which these units responded. Identical stimuli were used to test adaptation in the lateral shell of the central nucleus of the inferior colliculus (ICCls), which provides input directly to the ICX. Compared with ICX adaptation, adaptation in the ICCls was substantially weaker, shorter lasting, and far more frequency specific, suggesting that part of the adaptation observed in the ICX was attributable to processes resident to the ICX. The sharp tuning of ICX neurons to space, along with their broad tuning to frequency, allows ICX adaptation to preserve a representation of stimulus location, regardless of the frequency content of the sound. The ICX is known to be a site of visually guided auditory map plasticity. ICX adaptation could play a role in this cross-modal plasticity by providing a short-term memory of the representation of auditory localization cues that could be compared with later-arriving, visual–spatial information from bimodal stimuli.
Long-Term Potentiation Is Mediated by Multiple Kinase Cascades Involving CaMKII or Either PKA or p42/44 MAPK in the Adult Rat Dentate Gyrus In Vitro
Authors: Wu Jianqun , Rowan Michael J. , Anwyl Roger
Published: May 2006

The induction of NMDA-receptor–dependent long-term potentiation (LTP) in adult CA1 is contingent on activation of Ca/calmodulin-dependent protein kinase II (CaMKII). However, little is known about kinase mediation of LTP in the dentate gyrus. In the present study, the involvement of the kinases CaMKII, PKA, and MAPK in the induction of LTP was studied in the dentate gyrus of adult rats. Individual application of selective inhibitors of CaMKII, MEK, or PKA did not inhibit induction of LTP. In contrast, coapplication of a CaMKII inhibitor with either a PKA or MEK inhibitor resulted in a strong block of LTP. Induction of LTP was blocked by the coapplication of the inhibitors CaMKII and PKA or MEK, both when they were applied 1 h before the induction stimulus and also when they were applied after the induction stimulus. Thus LTP is mediated by either of two parallel cascades, one involving CaMKII and the other PKA or MAPK. Moreover, these cascades are active for a certain period after the induction stimulus.
Insulin Vesicle Release: Walk, Kiss, Pause … Then Run
Authors: Rutter Guy A. , Hill Elaine V.
Published: May 2006

The mechanisms by which insulin-containing dense core secretory vesicles approach and finally fuse with the plasma membrane are of considerable current interest: defects in these processes may be one of the contributing factors to Type 2 diabetes. In this review, we discuss the molecular mechanisms involved in vesicle trafficking within the pancreatic β-cell and the mechanisms whereby these may be regulated. We then go on to describe recent evidence that suggests that vesicle fusion at the plasma membrane is a partly reversible process (“kiss and run” or “cavity recapture”). We propose that vesicles may participate in a exo-endocytotic cycle in which a proportion of those that have already undergone an interaction with the plasma membrane may exchange exocytotic machinery with maturing vesicles.
Survival in Hostile Environments: Strategies of Renal Medullary Cells
Authors: Neuhofer Wolfgang , Beck Franz-X.
Published: May 2006

Cells in the renal medulla exist in a hostile milieu characterized by wide variations in extracellular solute concentrations, low oxygen tensions, and abundant reactive oxygen species. This article reviews the strategies adopted by these cells to allow them to survive and fulfill their functions under these extreme conditions.
Wnt/Frizzled Signaling in the Vasculature: New Angiogenic Factors in Sight
Authors: Masckauchán T. Néstor H. , Kitajewski Jan
Published: May 2006

Wnt growth factors function via Frizzled receptors to affect cellular proliferation, differentiation, apoptosis, and migration. Wnt/Frizzled signaling is now linked to human hereditary disorders with retinal vascular defects, implicating Wnts as angiogenic factors. Here, we discuss Wnts and a novel Frizzled ligand, Norrin, in physiological and pathological angiogenesis.
Dynamic Clamp Analyses of Cardiac, Endocrine, and Neural Function
Authors: Goaillard Jean-Marc , Marder Eve
Published: May 2006

The dynamic clamp introduces artificial conductances into cells to simulate electrical coupling, votage-dependent, leak, and synaptic conductances. This review describes how the dynamic clamp has been used to address various questions in the cardiac, endocrine, and nervous systems.
Astrocytes Coordinate Synaptic Networks: Balanced Excitation and Inhibition
Authors: Fellin Tommaso , Pascual Olivier , Haydon Philip G.
Published: May 2006

Although neurons are essential for brain function, an emerging alternative view holds that astrocytes, the dominant glial cell type, coordinate synaptic networks. Through the release of glutamate, astrocytes locally excite neurons, and via adenosine, which accumulates due to the hydrolysis of released ATP, astrocytes suppress distant synapses.
Do Grip and Pinch Strength Predict Neurologic Complications in Children with Spina Bifida and Hydrocephalus?
Authors: Liptak Gregory S. , Fried Ruth , Baltus-Hebert Elizabeth , Eyer Tierney Susan , Fucile Sandra , Doremus Tamara L.
Published: May 2006

Background: Neurological complications occur commonly in children with meningomyelocele and can cause significant morbidity and mortality. An earlier study suggested that acute changes in grip and pinch strength could be used to identify individuals at increased risk for developing a neurological complication. Objective: To evaluate the use of grip and pinch measurements to screen for neurological problems in children with spina bifida and hydrocephalus. Design: A prospective evaluation of screening tests. Patients: 92 children, born since 1976, who had meningomyelocele and hydrocephalus and were treated at the University of Rochester Medical Center. Methods: Grip and pinch strength were measured between July, 1991, and June, 2003. Results: Mean grip and pinch strengths were similar to those found in previous studies of children with meningomyelocele; 58 neurological events occurred in 39 (40%) individuals. These included 31 episodes of ventricular shunt failure and 22 symptomatic tethered cord occurrences. Specificity, sensitivity and likelihood ratios were calculated in multiple ways using different criteria for loss of grip or pinch strength and for interval to neurological event. Sensitivities were low (<0.35) and the highest positive likelihood ratio found, using fall in either lateral pinch with 6 months to neurological event, was 2.3. Conclusions: Despite previous recommendations, grip and pinch measurements were not helpful when used as a routine screening test for neurological dysfunction for children with meningomyelocele and hydrocephalus.
Paradoxical Response to Chemotherapy in Neurotuberculosis
Authors: Kumar Raj , Prakash Mahesh , Jha Sanjeev
Published: May 2006

Objective: Our objective was to investigate the paradoxical response and the factors responsible for such an uncommon (but known) response to chemotherapy in neurotuberculosis. Material and Methods: Ten children with intracranial tuberculomas/neurotuberculosis were retrospectively studied, who were on regular antituberculous chemotherapy. Any deterioration of the neurological condition, increase in the size of the lesion or appearance of new lesions was studied clinically and radiologically during the follow-up period. Results: An atypical response to chemotherapy was observed from 3 weeks to 1 year of chemotherapy. Four of the 10 children, who were receiving chemotherapy for either posttubercular meningitis (TBM), hydrocephalus (2) or TBM (2), developed multiple granulomas in 3 and hydrocephalus in 1 case. The remaining 6 children who were diagnosed to have granulomas at their presentation deteriorated at the follow-up despite regular chemotherapy. CT scans were repeated in 7 of 10 cases at the time of neurological deterioration, out of which 5 children showed appearance of new granulomas or abscess(es) and 2 showed an increase in the size of their preexisting granulomas. One patient with faintly enhancing granulomas in the posterior fossa responded to an additional use of steroids. The remaining 9 patients required surgical intervention on account of their neurological deterioration. Conclusions: (1) Paradoxical responses to intracranial tuberculoma/neurotuberculosis can occur at any time even up to 1 year during chemotherapy despite a regular standard antitubercular treatment. (2) New granuloma(s) or abscess(es) may appear in children receiving chemotherapy for TBM during the follow-up. (3) Hydrocephalus may also appear despite a regular chemotherapy in treated TBM cases. (4) Immature faintly enhancing tuberculomas have a more likely chance of resolution with antituberculous chemotherapy and glucocorticoids, while a well-formed and probably large-sized (>3 cm) granuloma may have a risk of paradoxical enlargement.
Aquaporin(s) Expression in Choroid Plexus Tumours
Authors: Longatti Pierluigi , Basaldella Luca , Orvieto Enrico , Dei Tos Angelo , Martinuzzi Andrea
Published: May 2006

Objective: It was the aim of this study to investigate the pattern of aquaporin 1 (AQP1) expression in normal and neoplastic choroid plexus, with specific reference to the association with communicating hydrocephalus or liquoral cysts. Second, to infer a new view on the cerebrospinal fluid plexus production and on the etiology of the cysts and communicating hydrocephalus occasionally associated with choroid plexus papillomas. Materials and Methods: Nineteen paraffin-embedded specimens, 10 of normal choroid plexus and 9 of choroid plexus tumours, were immunostained with a monoclonal antibody raised against the intracellular C-terminal AQP1 epitope. Results were analysed in terms of intensity and intracellular distribution of immunostaining and in terms of number of stained cells; they were considered in light of the clinical association with hydrocephalus or liquoral cysts. Results: AQP1 was heavily expressed in the apical side of the choroid epithelium in normal plexus specimens. Choroid plexus papillomas showed a very heterogeneous pattern of AQP1 expression. Immunostaining was absent in the case of choroid plexus carcinoma. Very strong to strong and diffuse AQP1 expression in large to very large papillomas was associated with liquoral cysts or communicating hydrocephalus. Conclusions: AQP1 expression characterizes normal choroid plexus and plexus papillomas. Intensity and diffusion of AQP1 expression together with the size of the tumour mass are somewhat predictive of communicating hydrocephalus or liquoral cyst, lesions possibly caused by a disturbance of cerebrospinal fluid homeostasis.
Hypothalamic Glioma Presenting with Seizures
Authors: Gupta D.K. , Satyarthee G.D. , Sharma M.C. , Mahapatra A.K.
Published: May 2006

A rare case of hypothalamic glioma in a 7-year-old boy presenting with seizures and diabetes insipidus is reported. Near total decompression of the hypothalamic glioma was done successfully using subfrontal approach. The patient had a stormy postoperative course due to status epilepticus but went on to make a complete recovery. Postoperative radiotherapy/chemotherapy was not given in view of tumor histology (low grade glioma), patient’s age and tumor location. Patient remains symptom and seizure free on antiepileptics at 3-year follow-up. The case is presented in the light of its rarity and the literature is reviewed.
Giant Hypothalamic Hamartoma Operated through Subfrontal Approach with Orbitary Rim Osteotomy
Authors: Miranda Pablo , Esparza Javier , Cabrera Antonio , Hinojosa Jose
Published: May 2006

Introduction: Hypothalamic hamartomas are associated with precocious puberty, gelastic seizures and severe refractory epilepsy. Treatment options include surgical resection, radiofrequency and radiosurgery. Case Report: A 7-month-old girl presented with gelastic seizures and developmental delay related to a giant hypothalamic hamartoma. The patient was operated through a subfrontal approach. Intraoperatively the lesion appeared intimately adherent to the right internal carotid artery. Seizure control was improved after tumoral decompression. Conclusions: Treatment of giant hypothalamic hamartomas should always include surgical resection, given the mass effect over surrounding vital structures. Subfrontal approach with orbitary rim osteotomy provides a wide exposure with minimal frontal lobe retraction. Close adherence of hypothalamic hamartoma to vascular structures may be present, requiring careful surgical manipulation.
A Case of Rudimentary Lateral Parietal Cephalocele: Extracranial Meningothelial and Glial Tissue without Intracranial Communication or Bony Defect
Authors: Hoh D. , Berry C. , Gonzalez I. , McComb J.G.
Published: May 2006

The authors report a case of a 7-month-old infant with a right lateral parietal scalp lesion intermittently leaking fluid similar to cerebrospinal fluid that histologically demonstrated meningothelial and glial cells. At surgical removal, however, no fibrous stalk or bony defect could be identified connecting the lesion with the intracranial compartment. While the embryologic mechanism of this lesion is unclear, the prognosis for normal neurological development appears excellent.
Evidence for Consistent Intragenic and Intergenic Interactions between SNP Effects in the APOA1/C3/A4/A5 Gene Cluster
Authors: Hamon Sara C. , Kardia Sharon L.R. , Boerwinkle Eric , Liu Kiang , Klos Kathy L.E. , Clark Andrew G. , Sing Charles F.
Published: May 2006

Objective: Evaluate the consistency of the contribution of interactions between single nucleotide polymorphism (SNP) genotype effects to variation in measures of lipid metabolism across ethnic strata within gender. Methods and Results: We considered 80 SNPs within the apolipoprotein (APO) A1/C3/A4/A5 gene cluster using an over-parameterized general linear model to identify SNPs whose genotype effects combine non-additively to influence plasma levels of high density lipoprotein cholesterol (HDL-C), total cholesterol (TC) and triglycerides (TG) in a consistent manner across ethnic strata. We analyzed population-based samples of unrelated 18 to 30 year old African-Americans (n = 1,858) and European-Americans (n = 1,973) ascertained without regard to health at four field centers (Birmingham, Ala.; Chicago, Ill.; Minneapolis, Minn. and Oakland, Calif., USA) by the Coronary Artery Risk Development in Young Adults (CARDIA) study. To identify which SNP genotype effects combine non-additively we used a two-tier analysis strategy. We first required that pairs of SNPs show statistically significant non-additivity in both ethnic strata within a gender, where experiment-wise significance was evaluated using a permutation test to determine the probability of observing the number of tests significant in both ethnic strata by chance alone. Second, we required no significant evidence of heterogeneity of the relationship between the phenotype and the two SNP genotypes across ethnic strata and across field centers within each ethnic group. From this strategy we identified ten pairs of SNPs, involving thirteen SNPs, that displayed statistically significant non-additivity of SNP genotype effects on TC. Only one of these thirteen SNPs had statistically significant genotype effects that were consistent across samples. Conclusion: Our analyses suggest that ignoring the contribution of interactions between SNP genotype effects when modeling multi-SNP genotype-phenotype relationships may result in an underestimate of the contribution of genetic variation to variation in quantitative cardiovascular disease (CVD) risk factor traits.
Comparison of the Test of Everyday Functional Abilities with a Direct Measure of Daily Function
Authors: Weiner Myron F. , Gehrmann Helena R. , Hynan Linda S. , Saine Kathleen C. , Cullum C. Munro
Published: May 2006

Objectives: To compare scores for dementia patients on a newly developed direct test of instrumental activities of daily living (IADLs) to scores on a widely accepted functional measure. Methods: In 27 community-dwelling dementia patients, scores for the Test of Everyday Functional Ability (TEFA) were compared with scores on a widely used direct test of daily function (Independent Living Scale; ILS). Results: Mini-Mental State Examination scores ranged from 5 to 28 (mean ± SD = 20.7 ± 6.37). There was a highly significant correlation between total TEFA and total ILS scores (r(25) = 0.892, p < 0.001) as well as many of the comparable subscales. Conclusion: The TEFA is a valid measure of IADL competence for dementia patients.
Opioid Analgesia for Hysterosalpingography: Controlled Double-Blind Prospective Trial with Remifentanil and Placebo
Authors: Cengiz Mustafa , Kafali Hasan , Artuc Hulya , Baysal Zeynep
Published: May 2006

Background/Aims: A hysterosalpingogram is an integral part of the evaluation of infertility, however, it is often painful. Methods: We conducted a randomized double-blinded, placebo-controlled trial of intravenous infusion of remifentanil in women undergoing hysterosalpingography (HSG). We randomly allocated 62 patients scheduled for HSG to receive either a continuous infusion of 0.25 µg·kg–1 of remifentanil or placebo. The degree of pain was documented via 10-cm visual analog scales (VAS). Patients’ discomfort, side effects and recovery times were also recorded. Results: The VAS scores during HSG were 1.25 ± 1.31 in the remifentanil group and 4.78 ± 1.7 in the placebo group (p < 0.001). There were more patients in the remifentanil group that rated their condition as excellent (p < 0.001). The groups did not differ with regard to the incidence of side effects. The recovery times were found statistically longer in the remifentanil group (14 ± 5 vs. 10 ± 3 min). All the patients were discharged 30 min after the procedures without any side effects. Conclusion: Remifentanil infusion during HSG is superior to placebo for relief of pain with minimal opioid side effects.