bluuebunny/crossref_metadata_2025 huggingface dataset:
Topology of Schwann cells and sympathetic innervation along preglomerular vessels: a confocal microscopic study in protein S100B/EGFP transgenic mice
Authors: Darlot Fannie , Artuso Annie , Lautredou-Audouy Nicole , Casellas Daniel
Published: October 2008

Schwann cells (Sc), associated axons, and nearby vascular endothelium constitute a functional trilogy of major importance during the development and regrowth of peripheral vascular nerves. The goal of the present study is to provide a technique of triple fluorescence confocal imaging of these cell types along renal preglomerular vessels. We took advantage of a protein S100B/EGFP transgenic mouse to visualize Sc. The endothelium was labeled with an intravenous injection of fluorescently tagged lectin, and after tissue processing, adrenergic nerves were revealed with an antibody against the marker protein synaptophysin. As a validation step, we found that EGFP-positive perivascular cells with prominent cell bodies and extensive, multidirectional cell processes were protein S100B positive. They were identified as Sc and indirectly assumed to be unmyelinated Sc. By contrast, we found strong EGFP expression in proximal epithelial cells and in the epithelium lining thin limbs of Henle. This epithelial fluorescence was not associated with immunoreactive protein S100B and thus corresponded to ectopic EGFP expressions in this mouse strain. Sc were organized in bundles or as a meshwork surrounding the preglomerular vasculature from arcuate arteries to afferent arterioles. No Sc were detected in the medulla. Although most Sc were closely apposed to adrenergic varicosities, many varicosities were not associated with detectable Sc processes. The present technique, and the capacity of confocal microscopy to yield three-dimensional imaging, allow the study of the microtopology of Sc and related sympathetic axons in the renal perivascular interstitium.
The reactive nitrogen species peroxynitrite is a potent inhibitor of renal Na-K-ATPase activity
Authors: Reifenberger Matthew S. , Arnett Krista L. , Gatto Craig , Milanick Mark A.
Published: October 2008

Peroxynitrite is a reactive nitrogen species produced when nitric oxide and superoxide react. In vivo studies suggest that reactive oxygen species and, perhaps, peroxynitrite can influence Na-K-ATPase function. However, the direct effects of peroxynitrite on Na-K-ATPase function remain unknown. We show that a single bolus addition of peroxynitrite inhibited purified renal Na-K-ATPase activity, with IC50of 107 ± 9 μM. To mimic cellular/physiological production of peroxynitrite, a syringe pump was used to slowly release (∼0.85 μM/s) peroxynitrite. The inhibition of Na-K-ATPase activity induced by this treatment was similar to that induced by a single bolus addition of equal cumulative concentration. Peroxynitrite produced 3-nitrotyrosine residues on the α, β, and FXYD subunits of the Na pump. Interestingly, the flavonoid epicatechin, which prevented tyrosine nitration, was unable to blunt peroxynitrite-induced ATPase inhibition, suggesting that tyrosine nitration is not required for inhibition. Peroxynitrite led to a decrease in iodoacetamidofluorescein labeling, implying that cysteine modifications were induced. Glutathione was unable to reverse ATPase inhibition. The presence of Na+and low MgATP during peroxynitrite treatment increased the IC50to 145 ± 10 μM, while the presence of K+and low MgATP increased the IC50to 255 ± 13 μM. This result suggests that the EPNa conformation of the pump is slightly more sensitive to peroxynitrite than the E(K) conformation. Taken together, these results show that peroxynitrite is a potent inhibitor of Na-K-ATPase activity and that peroxynitrite can induce amino acid modifications to the pump.
Trafficking of Na-K-ATPase and dopamine receptor molecules induced by changes in intracellular sodium concentration of renal epithelial cells
Authors: Cinelli Angel R. , Efendiev Riad , Pedemonte Carlos H.
Published: October 2008

Most of the transepithelial transport of sodium in proximal tubules occurs through the coordinated action of the apical sodium/proton exchanger and the basolateral Na-K-ATPase. Hormones that regulate proximal tubule sodium excretion regulate the activities of these proteins. We have previously demonstrated that the level of intracellular sodium concentration modulates the regulation of Na-K-ATPase activity by angiotensin II and dopamine. An increase of a few millimolars in intracellular sodium concentration leads to increased Na-K-ATPase activity without a statistically significant increase in the number of plasma membrane Na-K-ATPase molecules, as determined by cell surface protein biotinylation. Using total internal reflection fluorescence, we detected an increased number of Na-K-ATPase molecules in cytosolic compartments adjacent to the plasma membrane, suggesting that the increased intracellular sodium concentration induces a movement of Na-K-ATPase molecules toward the plasma membrane. While intracellular compartments containing Na-K-ATPase molecules are very close to the plasma membrane, compartments containing type 1 dopamine receptors (D1Rs) are distributed in different parts of the cell cytosol. Fluorescence determinations indicate that an increased intracellular sodium concentration induces the increased colocalization of dopamine receptors with Na-K-ATPase molecules in the region of the plasma membrane. We propose that under in vivo conditions, in response to a sodium load in the lumen of proximal tubules, an increased level of intracellular sodium in epithelial cells is an early event that triggers the cellular response that leads to dopamine inhibition of proximal tubule sodium reabsorption.
Salt sensitivity of blood pressure in NKCC1-deficient mice
Authors: Kim Soo Mi , Eisner Christoph , Faulhaber-Walter Robert , Mizel Diane , Wall Susan M. , Briggs Josephine P. , Schnermann Jurgen
Published: October 2008

NKCC1 is a widely expressed isoform of the Na-2Cl-K cotransporter that mediates several direct and indirect vascular effects and regulates expression and release of renin. In this study, we used NKCC1-deficient (NKCC1−/−) and wild-type (WT) mice to assess day/night differences of blood pressure (BP), locomotor activity, and renin release and to study the effects of high (8%) or low (0.03%) dietary NaCl intake on BP, activity, and the renin/aldosterone system. On a standard diet, 24-h mean arterial blood pressure (MAP) and heart rate determined by radiotelemetry, and their day/night differences, were not different in NKCC1−/−and WT mice. Spontaneous and wheel-running activities in the active night phase were lower in NKCC1−/−than WT mice. In NKCC1−/−mice on a high-NaCl diet, MAP increased by 10 mmHg in the night without changes in heart rate. In contrast, there was no salt-dependent blood pressure change in WT mice. MAP reductions by hydralazine (1 mg/kg) or isoproterenol (10 μg/mouse) were significantly greater in NKCC1−/−than WT mice. Plasma renin (PRC; ng ANG I·ml−1·h−1) and aldosterone (aldo; pg/ml) concentrations were higher in NKCC1−/−than WT mice (PRC: 3,745 ± 377 vs. 1,245 ± 364; aldo: 763 ± 136 vs. 327 ± 98). Hyperreninism and hyperaldosteronism were found in NKCC1−/−mice during both day and night. High Na suppressed PRC and aldosterone in both NKCC1−/−and WT mice, whereas a low-Na diet increased PRC and aldosterone in WT but not NKCC1−/−mice. We conclude that 24-h MAP and MAP circadian rhythms do not differ between NKCC1−/−and WT mice on a standard diet, probably reflecting a balance between anti- and prohypertensive factors, but that blood pressure of NKCC1−/−mice is more sensitive to increases and decreases of Na intake.
WNK3 and WNK4 amino-terminal domain defines their effect on the renal Na+-Cl−cotransporter
Authors: San-Cristobal Pedro , Ponce-Coria José , Vázquez Norma , Bobadilla Norma A. , Gamba Gerardo
Published: October 2008

Loss of physiological regulation of the renal thiazide-sensitive Na+-Cl−cotransporter (NCC) by mutant WNK1 or WNK4 results in pseudohypoaldosteronism type II (PHAII) characterized by arterial hypertension and hyperkalemia. WNK4 normally inhibits NCC, but this effect is lost by eliminating WNK4 catalytic activity or through PHAII-type mutations. In contrast, another member of the WNK family, WNK3, activates NCC. The positive effect of WNK3 on NCC also requires its catalytic activity. Because the opposite effects of WNK3 and WNK4 on NCC were observed in the same expression system, sequences within the WNKs should endow these kinases with their activating or inhibiting properties. To gain insight into the structure-function relationships between the WNKs and NCC, we used a chimera approach between WNK3 and WNK4 to elucidate the domain of the WNKs responsible for the effects on NCC. Chimeras were constructed by swapping the amino or carboxyl terminus domains, which flank the central kinase domain, between WNK3 and WNK4. Our results show that the effect of chimeras toward NCC follows the amino-terminal domain. Thus the amino terminus of the WNKs contains the sequences that are required for their activating or inhibiting properties on NCC.
Otolithic activation on visceral circulation in humans: effect of aging
Authors: Sauder Charity L. , Conboy Erin E. , Chin-Sang Stephanie A. , Ray Chester A.
Published: October 2008

Engagement of the otolith organs elicits differential activation of sympathetic nerve activity and vascular responses to muscle and skin in humans. Additionally, aging attenuates the otolith organ-mediated increases in muscle sympathetic nerve activity in older adults. In this study, we hypothesized that 1) the vestibulosympathetic reflex (VSR) would elicit visceral vascular vasoconstriction and 2) visceral vascular response to the VSR would be attenuated in older subjects compared with young. To test these hypotheses, heart rate, mean arterial blood pressure, and renal, celiac trunk, and superior mesenteric arterial blood velocity (Doppler ultrasound) were measured in 22 young (25 ± 1 yr) and 18 older (65 ± 2 yr) healthy subjects during head-down rotation (HDR), which selectively activates the otolith organs. Mean arterial pressure and heart rate did not change from baseline during HDR in young or older subjects. Renal blood velocity (Δ −2 ± 1 cm/s) and vascular conductance (Δ −0.03 ± 0.01 cm·s−1·mmHg−1) significantly decreased from baseline during HDR ( P < 0.05) in young subjects. In contrast, renal blood velocity and conductance did not change in older subjects (Δ −0.2 ± 1 cm/s and Δ0.02 ± 0.08 mmHg·cm−1·s−1, respectively) during HDR. Superior mesenteric and celiac blood velocity and vascular conductance did not change in response to HDR in either the young or older subjects. These data suggest that renal vasoconstriction occurs during otolith organ activation in young but not older humans. Together with our previous studies, we conclude that the VSR elicits a diverse patterning of sympathetic outflow that results in heterogeneous vascular responses in humans and that these responses are significantly attenuated in older humans.
Conditional fast expression and function of multimeric TRPV5 channels using Shield-1
Authors: Schoeber Joost P. H. , van de Graaf Stan F. J. , Lee Kyu Pil , Wittgen Hanneke G. M. , Hoenderop Joost G. J. , Bindels René J. M.
Published: October 2008

A recently described novel controllable method to regulate protein expression is based on a mutated FK506-binding protein-12 (mtFKBP) that is unstable and rapidly degraded in mammalian cells. This instability can be conferred to other proteins directly fused to mtFKBP. Binding of a synthetic cell-permeant ligand (Shield-1) to mtFKBP reverses the instability, allowing conditional expression of mtFKBP-fused proteins. We adapted this strategy to study multimeric plasma membrane proteins using the ion channel TRPV5 as model protein. mtFKBP-TRPV5 forms functional ion channels and its expression can be controlled in a time- and dose-dependent fashion using Shield-1. Moreover, in the presence of Shield-1, mtFKBP-TRPV5 formed heteromultimeric channels with untagged TRPV5, which were codegraded upon washout of Shield-1, providing a strategy to study multimeric plasma membrane protein complexes without the need to destabilize all individual subunits.
Loop of Henle interaction with interstitial nodal spaces in the renal inner medulla
Authors: Pannabecker Thomas L.
Published: October 2008

Understanding dynamics of NaCl reabsorption from loops of Henle, and cellular and physiological consequences, requires a clear understanding of the structural relationships of loops with other functional elements of the inner medulla (IM). Pathways taken by ascending thin limbs (ATLs) and prebend segments along the corticopapillary axis were evaluated for the outer zone of the IM of the Munich-Wistar rat. Connectivity between these segments and microdomains of interstitium adjacent to collecting ducts (CDs) and abutting ascending vasa recta (interstitial nodal spaces) was assessed by evaluating their physical contacts. For each secondary CD cluster, the number of contacts made between the total population of ATLs and interstitial nodal spaces declines as a function of depth below the outer medulla (OM)-IM boundary at near the same exponential rate that loop number declines. The proportion of each loop that makes contact with nodal spaces is inversely related to loop length. Prebend and postbend equivalent length ATL segments lie in contact with an interstitial nodal space along nearly their entire lengths. The number of contacts made by the total population of prebend or postbend segments exhibits a marked, periodic increase and decrease as a function of depth below the OM-IM boundary; this number of contacts correlates with equivalent periodic changes in prebend number. Simulations of loop distribution indicate that small discontinuities in loop distribution contribute to periodic changes in prebend number. Convergence of IM loop bends within CD clusters likely plays an essential role in NaCl compartmentalization by promoting NaCl reabsorption near interstitial regions lying adjacent to CDs and ascending vasa recta.
Role of p75NTR in female rat urinary bladder with cyclophosphamide-induced cystitis
Authors: Klinger Mary Beth , Vizzard Margaret A.
Published: October 2008

Previous studies demonstrated changes in urinary bladder neurotrophin content and upregulation of neurotrophin receptors, TrkA and the p75 neurotrophin receptor (p75NTR), in micturition reflex pathways after cyclophosphamide (CYP)-induced cystitis. p75NTR can bind nerve growth factor (NGF) and modulate NGF-TrkA binding and signaling. We examined p75NTR expression and the role of p75NTR in the micturition reflex in control and CYP-treated rats. p75NTR Immunoreactivity was present throughout the urinary bladder. CYP-induced cystitis (4 h, 48 h, chronic) increased ( P ≤ 0.05) p75NTR expression in whole urinary bladder as shown by Western blotting. The role of p75NTR in bladder function in control and CYP-treated rats was determined using conscious cystometry and immunoneutralization or PD90780, a compound known to specifically block NGF binding to p75NTR. An anti-p75NTR monoclonal antibody or PD90780 was infused intravesically and cystometric parameters were evaluated. Both methods of p75NTR blockade significantly ( P ≤ 0.05) decreased the intercontraction interval and void volume in control and CYP-treated rats. Intravesical infusion of PD90780 also significantly ( P ≤ 0.001) increased intravesical pressure and increased the number of nonvoiding contractions during the filling phase. Control intravesical infusions of isotype-matched IgG and vehicle were without effect. Intravesical instillation of PD90780 significantly ( P ≤ 0.01) reduced the volume threshold to elicit a micturition contraction in control rats (no inflammation) and CYP-treated in a closed urinary bladder system. These studies demonstrate 1) ubiquitous p75NTR expression in urinary bladder and increased expression with CYP-induced cystitis and 2) p75NTR blockade at the level of the urinary bladder produces bladder hyperreflexia in control and CYP-treated rats. The overall activity of the urinary bladder reflects the balance of NGF-p75NTR and NGF-TrkA signaling.
Glomerular epithelial cells in the urine: what has to be done to make them worthwhile?
Authors: Skoberne Andrej , Konieczny Andrzej , Schiffer Mario
Published: October 2008

The significance of the native urine sediment in the differential of glomerular diseases needs no further comment. However, the question arises whether it could be useful to develop a more specific diagnostic approach to identify the origin of renal epithelial cells that can be detected in the urine sediments as well. Especially the detection of podocytes in the urine could be a valuable noninvasive method to get information about the disease activity or disease type and could be used as a follow-up after a biopsy in an outpatient setting. So far, there are only a few studies that analyzed the clinical relevance of renal epithelial cells in the urine systematically or prospectively. The reason for this could be the nature of the material since it will remain unclear whether detachment and changes in the urine milieu have a direct effect on the expression of marker proteins on the detected cells. Dedifferentiation or transdifferentiation of cells that goes along with changed marker expression is certainly also part of the underlying disease process. This review summarizes the available information on marker proteins that have been successfully used in the diagnostic of “podocytes” in the urine. Furthermore, it gives an overview of marker expression on podocytes in situ in development and disease and examines the role of glomerular epithelial shedding in the urine at the interface of basic science and clinical medicine.
Transfer of the CYP4A region of chromosome 5 from Lewis to Dahl S rats attenuates renal injury
Authors: Williams Jan Michael , Sarkis Albert , Hoagland Kimberly M. , Fredrich Katherine , Ryan Robert P. , Moreno Carol , Lopez Bernardo , Lazar Jozef , Fenoy Francisco J. , Sharma Mukut , Garrett Michael R. , Jacob Howard J. , Roman Richard J.
Published: October 2008

This study examined the effect of transfer of overlapping regions of chromosome 5 that includes (4A+) or excludes (4A−) the cytochrome P-450 4A (CYP4A) genes from the Lewis rat on the renal production of 20-hydroxyeicosatetraenoic acid (20-HETE) and the development of hypertension-induced renal disease in congenic strains of Dahl salt-sensitive (Dahl S) rats. The production of 20-HETE was higher in the outer medulla of 4A+than in Dahl S or 4A−rats. Mean arterial pressure (MAP) rose to 190 ± 7 and 185 ± 3 mmHg in Dahl S and 4A−rats fed a high-salt (HS) diet for 21 days but only to 150 ± 5 mmHg in the 4A+strain. Protein excretion increased to 423 ± 40 and 481 ± 37 mg/day in Dahl S and 4A−rats vs. 125 ± 15 mg/day in the 4A+strain. Baseline glomerular capillary pressure (Pgc) was lower in 4A+rats (38 ± 1 mmHg) than in Dahl S rats (42 ± 1 mmHg). Pgc increased to 50 ± 1 mmHg in Dahl S rats fed a HS diet, whereas it remained unaltered in 4A+rats (39 ± 1 mmHg). Baseline glomerular permeability to albumin ( Palb) was lower in 4A+rats (0.19 ± 0.05) than in Dahl S or 4A−rats (0.39 ± 0.02). Palbrose to ∼0.61 ± 0.03 in 4A−and Dahl S rats fed a HS diet for 7 days, but it remained unaltered in the 4A+rats. The expression of transforming growth factor-β2 was higher in glomeruli of Dahl S rats than in 4A+rats fed either a low-salt (LS) or HS diet. Chronic administration of a 20-HETE synthesis inhibitor (HET0016; 10 mg·kg−1·day−1sc) reversed the fall in MAP and renoprotection seen in 4A+rats. These results indicate that the introgression of the CYP4A genes from Lewis rats into the Dahl S rats increases the renal formation of 20-HETE and attenuates the development of hypertension and renal disease.
Plasma NT-proBNP increases in response to LPS administration in healthy men
Authors: Vila Greisa , Resl Michael , Stelzeneder David , Struck Joachim , Maier Christina , Riedl Michaela , Hülsmann Martin , Pacher Richard , Luger Anton , Clodi Martin
Published: October 2008

Circulating levels of B-type natriuretic peptide (BNP) and NH2-terminal-proBNP (NT-proBNP) increase in response to volume overload and help in the differential diagnosis of acute heart failure. Elevated plasma BNP levels are observed also in sepsis and do not always correspond to left ventricular dysfunction. Here, we investigated plasma NT-proBNP fluctuations in response to human bacterial endotoxinemia, an experimental model of systemic infection and inflammation. Escherichia coli endotoxin (LPS) (2 ng/kg) was administered to 10 healthy volunteers in a randomized, placebo-controlled, cross-over design. Plasma NT-proBNP, C-reactive protein (CRP), COOH terminal pro-endothelin-1 (CT-proET-1), and midregional-pro-adrenomedullin (MR-proADM) were measured at hourly intervals for 6 h. LPS administration induced a continuous increase in plasma NT-proBNP that reached peak values after 6 h (40.7 ± 7.9 vs. 16.1 ± 3.2 pg/ml in placebo days, mean ± SE; P = 0.023). The profile of changes in NT-proBNP correlated to changes in body temperature ( P < 0.001), heart rate ( P = 0.005), CRP ( P < 0.001), and CT-proET-1 ( P = 0.008), but not to blood pressure values. Our results demonstrate that plasma NT-proBNP increases in a model of systemic infection/inflammation in healthy men with normal heart function. This finding emphasizes the necessity to consider concomitant infections when interpreting elevated circulating NT-proBNP concentrations.
Resistance exercise increases human skeletal muscle AS160/TBC1D4 phosphorylation in association with enhanced leg glucose uptake during postexercise recovery
Authors: Dreyer Hans C. , Drummond Micah J. , Glynn Erin L. , Fujita Satoshi , Chinkes David L. , Volpi Elena , Rasmussen Blake B.
Published: October 2008

Akt substrate of 160 kDa (AS160/TBC1D4) is associated with insulin and contraction-mediated glucose uptake. Human skeletal muscle AS160 phosphorylation is increased during aerobic exercise but not immediately following resistance exercise. It is not known whether AS160 phosphorylation is altered during recovery from resistance exercise. Therefore, we hypothesized that muscle AS160/TBC1D4 phosphorylation and glucose uptake across the leg would be increased during recovery following resistance exercise. We studied 9 male subjects before, during, and for 2 h of postexercise recovery. We utilized femoral catheterizations and muscle biopsies in combination with indirect calorimetry and immunoblotting to determine whole body glucose and fat oxidation, leg glucose uptake, muscle AMPKα2 activity, and the phosphorylation of muscle Akt and AS160/TBC1D4. Glucose oxidation was reduced while fat oxidation increased (∼35%) during postexercise recovery ( P ≤ 0.05). Glucose uptake increased during exercise and postexercise recovery ( P ≤ 0.05). Akt phosphorylation was increased at 1 h and AMPKα2 activity increased at 2 h postexercise ( P ≤ 0.05). Phospho(Ser/Thr)-Akt substrate (PAS) phosphorylation (often used as a marker for AS160) was unchanged immediately postexercise and increased at 1 h ( P ≤ 0.05) and 2 h postexercise ( P = 0.07). The PAS antibody is not always specific for AS160/TBC1D4 and can detect proteins at a similar molecular weight. Therefore, we immunoprecipitated AS160/TBC1D4 and then blotted with the PAS antibody, which confirmed that PAS phosphorylation is occurring on AS160/TBC1D4. There was also a positive correlation between PAS phosphorylation and leg glucose uptake during recovery ( P < 0.05). We conclude that resistance exercise increases AS160/TBC1D4 phosphorylation in association with an increase in leg glucose uptake during postexercise recovery.
Effects of antioxidants on contracting spinotrapezius muscle microvascular oxygenation and blood flow in aged rats
Authors: Herspring Kyle F. , Ferreira Leonardo F. , Copp Steven W. , Snyder Brian S. , Poole David C. , Musch Timothy I.
Published: October 2008

Aged rats exhibit a decreased muscle microvascular O2 partial pressure (PmvO2) at rest and during contractions compared with young rats. Age-related reductions in nitric oxide bioavailability due, in part, to elevated reactive O2 species, constrain muscle blood flow (Q̇m). Antioxidants may restore nitric oxide bioavailability, Q̇m, and ameliorate the reduced PmvO2. We tested the hypothesis that antioxidants would elevate Q̇m and, therefore, PmvO2 in aged rats. Spinotrapezius muscle PmvO2 and Q̇m were measured, and oxygen consumption (V̇mO2) was estimated in anesthetized male Fisher 344 × Brown Norway hybrid rats at rest and during 1-Hz contractions, before and after antioxidant intravenous infusion (76 mg/kg vitamin C and 52 mg/kg tempol). Before infusion, contractions evoked a biphasic PmvO2 that fell from 30.6 ± 0.9 Torr to a nadir of 16.8 ± 1.2 Torr with an “undershoot” of 2.8 ± 0.7 Torr below the subsequent steady-state (19.7 ± 1.2 Torr). The principal effect of antioxidants was to elevate baseline PmvO2 from 30.6 ± 0.9 to 35.7 ± 0.8 Torr ( P < 0.05) and reduce or abolish the undershoot ( P < 0.05). Antioxidants reduced Q̇m and V̇mO2 during contractions ( P < 0.05), while decreasing force production 16.5% ( P < 0.05) and elevating the force production-to-V̇mO2 ratio (0.92 ± 0.03 to 1.06 ± 0.6, P < 0.05). Thus antioxidants increased PmvO2 by altering the balance between muscle O2 delivery and V̇mO2 at rest and during contractions. It is likely that this effect arose from antioxidants reducing myocyte redox below the level optimal for contractile performance and directly (decreased tension) or indirectly (altered balance of vasoactive mediators) influencing O2 delivery and V̇mO2.
Early Stages of Melody Processing: Stimulus-Sequence and Task-Dependent Neuronal Activity in Monkey Auditory Cortical Fields A1 and R
Authors: Yin Pingbo , Mishkin Mortimer , Sutter Mitchell , Fritz Jonathan B.
Published: October 2008

To explore the effects of acoustic and behavioral context on neuronal responses in the core of auditory cortex (fields A1 and R), two monkeys were trained on a go/no-go discrimination task in which they learned to respond selectively to a four-note target (S+) melody and withhold response to a variety of other nontarget (S−) sounds. We analyzed evoked activity from 683 units in A1/R of the trained monkeys during task performance and from 125 units in A1/R of two naive monkeys. We characterized two broad classes of neural activity that were modulated by task performance. Class I consisted of tone-sequence–sensitive enhancement and suppression responses. Enhanced or suppressed responses to specific tonal components of the S+ melody were frequently observed in trained monkeys, but enhanced responses were rarely seen in naive monkeys. Both facilitatory and suppressive responses in the trained monkeys showed a temporal pattern different from that observed in naive monkeys. Class II consisted of nonacoustic activity, characterized by a task-related component that correlated with bar release, the behavioral response leading to reward. We observed a significantly higher percentage of both Class I and Class II neurons in field R than in A1. Class I responses may help encode a long-term representation of the behaviorally salient target melody. Class II activity may reflect a variety of nonacoustic influences, such as attention, reward expectancy, somatosensory inputs, and/or motor set and may help link auditory perception and behavioral response. Both types of neuronal activity are likely to contribute to the performance of the auditory task.
Effects of Odor Stimulation on Antidromic Spikes in Olfactory Sensory Neurons
Authors: Scott John W. , Sherrill Lisa
Published: October 2008

Spikes were evoked in rat olfactory sensory neuron (OSN) populations by electrical stimulation of the olfactory bulb nerve layer in pentobarbital anesthetized rats. The latencies and recording positions for these compound spikes showed that they originated in olfactory epithelium. Dual simultaneous recordings indicated conduction velocities in the C-fiber range, around 0.5 m/s. These spikes are concluded to arise from antidromically activated olfactory sensory neurons. Electrical stimulation at 5 Hz was used to track changes in the size and latency of the antidromic compound population spike during the odor response. Strong odorant stimuli suppressed the spike size and prolonged its latency. The latency was prolonged throughout long odor stimuli, indicating continued activation of olfactory receptor neuron axons. The amounts of spike suppression and latency change were strongly correlated with the electroolfactogram (EOG) peak size evoked at the same site across odorants and across stimulus intensities. We conclude that the curve of antidromic spike suppression gives a reasonable representation of spiking activity in olfactory sensory neurons driven by odorants and that the correlation of peak spike suppression with the peak EOG shows the accuracy of the EOG as an estimate of intracellular potential in the population of olfactory sensory neurons. In addition, these results have important implications about traffic in olfactory nerve bundles. We did not observe multiple peaks corresponding to stimulated and unstimulated receptor neurons. This suggests synchronization of spikes in olfactory nerve, perhaps by ephaptic interactions. The long-lasting effect on spike latency shows that action potentials continue in the nerve throughout the duration of an odor stimulus in spite of many reports of depolarization block in olfactory receptor neuron cell bodies. Finally, strong odor stimulation caused almost complete block of antidromic spikes. This indicates that a very large proportion of olfactory axons was activated by single strong odor stimuli.
Encoding by Response Duration in the Basal Ganglia
Authors: Parush Naama , Arkadir David , Nevet Alon , Morris Genela , Tishby Naftali , Nelken Israel , Bergman Hagai
Published: October 2008

Several models have suggested that information transmission in the basal ganglia (BG) involves gating mechanisms, where neuronal activity modulates the extent of gate aperture and its duration. Here, we demonstrate that BG response duration is informative about a highly abstract stimulus feature and show that the duration of “gate opening” can indeed be used for information transmission through the BG. We analyzed recordings from three BG locations: the external part of the globus pallidus (GPe), the substantia nigra pars reticulata (SNr), and dopaminergic neurons from the substantia nigra pars compacta (SNc) during performance of a probabilistic visuomotor task. Most (>85%) of the neurons showed significant rate modulation following the appearance of cues predicting future reward. Trial-to-trial mutual information analysis revealed that response duration encoded reward prospects in many (42%) of the responsive SNr neurons, as well as in the SNc (26.9%), and the GPe (29.3%). Whereas the low-frequency discharge SNc neurons responded with only an increase in firing rate, SNr and GPe neurons with high-frequency tonic discharge responded with both increases and decreases. Conversely, many duration-informative neurons in SNr (68%) and GPe (50%) responded with a decreased rather than an increased rate. The response duration was more informative than the extreme (minimal or maximal) amplitude or spike count in responsive bins of duration-informative neurons. Thus response duration is not simply correlated with the discharge rate and can provide additional information to the target structures of the BG.
BDNF Modulation of NMDA Receptors Is Activity Dependent
Authors: Crozier Robert A. , Bi Caixia , Han Yu R. , Plummer Mark R.
Published: October 2008

Brain-derived neurotrophic factor (BDNF), a potent modulator of synaptic transmission, is known to influence associative synaptic plasticity and refinement of neural connectivity. We now show that BDNF modulation of glutamate currents in hippocampal neurons exhibits the additional property of use dependence, a postsynaptic mechanism resulting in selective modulation of active channels. We demonstrate selectivity by varying the repetition rate of iontophoretically applied glutamate pulses during BDNF exposure. During relatively high-frequency glutamate pulses (0.1 Hz), BDNF application elicited a doubling of the glutamate current. During low-frequency pulses (0.0033 Hz), however, BDNF evoked a dramatically diminished response. This effect was apparently mediated by calcium because manipulations that prevented elevation of intracellular calcium largely eliminated the action of BDNF on glutamate currents. To confirm N-methyl-d-aspartate (NMDA) receptor involvement and assess spatial requirements, we made cell-attached single-channel recordings from somatic NMDA receptors. Inclusion of calcium in the pipette was sufficient to produce enhancement of channel activity by BDNF. Substitution of EGTA for calcium prevented BDNF effects. We conclude that BDNF modulation of postsynaptic NMDA receptors requires concurrent neuronal activity potentially conferring synaptic specificity on the neurotrophin's actions.
Differential Effects of Divalent Cations on Spontaneous and Evoked Glycine Release From Spinal Interneurons
Authors: Maeda Megumi , Tanaka Eiichiro , Shoudai Kiyomitsu , Nonaka Kiku , Murayama Nobuki , Ito Yushi , Akaike Norio
Published: October 2008

The effects of Ca2+, Sr2+, and Ba2+on spontaneous and evoked glycinergic inhibitory postsynaptic currents (mIPSCs and eIPSCs) were studied using the “synaptic bouton” preparation of rat spinal neurons and conventional whole cell recording under voltage-clamp conditions. In response to application of Ca2+-free solution, the frequency of mIPSC initially rapidly decreased to 40∼50% of control followed by a gradual further decline in mIPSC frequency to ∼30% of control. Once mIPSC frequency had significantly decreased in Ca2+-free solution, application of Ca2+, Sr2+, or Ba2+increased mIPSC frequency. The rank order of effect in restoring mIPSCs was Ba2+≫ Ca2+> Sr2+. Moreover, the application of excess external [K+]osolution (30 mM) containing Sr2+or Ba2+after 2 h in Ca2+-free solution also increased mIPSC frequency in the order Sr2+≧ Ba2+> Ca2+. The mean mIPSC amplitude was not affected at all. In contrast, eIPSCs produced by focal stimulation of single boutons were completely abolished in Ca2+-free solution or when Ca2+was replaced by Sr2+or Ba2+(2 mM each). However, eIPSCs were restored in increased concentrations of Sr2+or Ba2+(5 mM each). The results show that these divalent cations affect mIPSC and eIPSCs differently and indicate that the mechanisms underlying transmitter release that generates eIPSCs and mIPSC in presynaptic nerve terminals are different. The different mechanisms might be explained by the different sensitivity of synaptotagmin isoforms to Ca2+, Sr2+, and Ba2+.
Effects of Axotomy on Cultured Sensory Neurons ofAplysia: Long-Term Injury-Induced Changes in Excitability and Morphology Are Mediated by Different Signaling Pathways
Authors: Bedi Supinder S. , Cai Diancai , Glanzman David L.
Published: October 2008

To facilitate an understanding of injury-induced changes within the nervous system, we used a single-cell, in vitro model of axonal injury. Sensory neurons were individually dissociated from the CNS of Aplysia and placed into cell culture. The major neurite of some neurons was then transected (axotomized neurons). Axotomy in hemolymph-containing culture medium produced long-term hyperexcitability (LTH-E) and enhanced neuritic sprouting (long-term hypermorphogenesis [LTH-M]). Axotomy in the absence of hemolymph induced LTH-E, but not LTH-M. Hemolymph-derived growth factors may activate tyrosine receptor kinase (Trk) receptors in sensory neurons. To examine this possibility, we treated uninjured (control) and axotomized sensory neurons with K252a, an inhibitor of Trk receptor activity. K252a depressed the excitability of both axotomized and control neurons. K252a also produced a distinct pattern of arborizing outgrowth of neurites in both axotomized and control neurons. Protein kinase C (PKC) is an intracellular signal downstream of Trk; accordingly, we tested the effects of bisindolylmaleimide I (Bis-I), a specific inhibitor of PKC, on the axotomy-induced cellular changes. Bis-I blocked LTH-E, but did not disrupt LTH-M. Finally, because Trk activates the extracellular signal regulated kinase pathway in Aplysia sensory neurons, we examined whether this pathway mediates the injury-induced changes. Sensory neurons were axotomized in the presence of U0126, an inhibitor of mitogen-activated/extracellular receptor-regulated kinase. U0126 blocked the LTH-M due to axotomy, but did not impair LTH-E. Therefore distinct cellular signaling pathways mediate the induction of LTH-E and LTH-M in the sensory neurons.
Computational Approaches to Spatial Orientation: From Transfer Functions to Dynamic Bayesian Inference
Authors: MacNeilage Paul R. , Ganesan Narayan , Angelaki Dora E.
Published: October 2008

Spatial orientation is the sense of body orientation and self-motion relative to the stationary environment, fundamental to normal waking behavior and control of everyday motor actions including eye movements, postural control, and locomotion. The brain achieves spatial orientation by integrating visual, vestibular, and somatosensory signals. Over the past years, considerable progress has been made toward understanding how these signals are processed by the brain using multiple computational approaches that include frequency domain analysis, the concept of internal models, observer theory, Bayesian theory, and Kalman filtering. Here we put these approaches in context by examining the specific questions that can be addressed by each technique and some of the scientific insights that have resulted. We conclude with a recent application of particle filtering, a probabilistic simulation technique that aims to generate the most likely state estimates by incorporating internal models of sensor dynamics and physical laws and noise associated with sensory processing as well as prior knowledge or experience. In this framework, priors for low angular velocity and linear acceleration can explain the phenomena of velocity storage and frequency segregation, both of which have been modeled previously using arbitrary low-pass filtering. How Kalman and particle filters may be implemented by the brain is an emerging field. Unlike past neurophysiological research that has aimed to characterize mean responses of single neurons, investigations of dynamic Bayesian inference should attempt to characterize population activities that constitute probabilistic representations of sensory and prior information.
The Preparation and Characterization of β‐SiAlON Nanostructure Whiskers
Authors: Dong Pengli , Wang Xidong , Zhang Mei , Guo Min , Seetharaman Seshadri
Published: October 2008

Two kinds of β‐SiAlON nanostructure whiskers, rod‐like and wool‐like whiskers, were synthesized by pressure‐less sintering method at 1773 K for 5 hours. The whiskers synthesized were characterized by powder X‐ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), and high‐resolution electron microscope (HREM) techniques. It was found that diameter distribution of rod‐like whiskers was about 80–250 nm, while it was about 45–55 nm in diameter for the wool‐like whiskers. The growth mechanisms of β‐SiAlON nanostructure whiskers are discussed by the
vapor‐solid (VS) and vapor‐liquid‐solid (VLS)
mechanisms, respectively.
Characterizing Vibrating Cantilevers for Liquid Viscosity and Density Sensing
Authors: Riesch Christian , Reichel Erwin K. , Keplinger Franz , Jakoby Bernhard
Published: October 2008

Miniaturized liquid sensors are essential devices in online process or condition monitoring. In case of viscosity and density sensing, microacoustic sensors such as quartz crystal resonators or SAW devices have proved particularly useful. However, these devices basically measure a thin‐film viscosity, which is often not comparable to the macroscopic parameters probed by conventional viscometers. Miniaturized cantilever‐based devices are interesting alternatives for such applications, but here the interaction between the liquid and the oscillating beam is more involved. In our contribution, we describe a measurement setup, which allows the investigation of this interaction for different beam cross‐sections. We present an analytical model based on an approximation of the immersed cantilever as an oscillating sphere comprising the effective mass and the intrinsic damping of the cantilever and additional mass and damping due to the liquid loading. The model parameters are obtained from measurements with well‐known sample liquids by a curve fitting procedure. Finally, we present the measurement of viscosity and density of an unknown sample liquid, demonstrating the feasibility of the model.
Global Synthesis Method for the Optimization of Multifeed EBG Antennas
Authors: Drouet Julien , Thevenot Marc , Chantalat Régis , Menudier Cyrille , Koubeissi Majed , Monédière Thierry , Jecko Bernard
Published: October 2008

This paper presents a novel technique for synthesizing a given radiation pattern from an EBG antenna with an array feed. The method determines the optimum sets of input waves and input impedances for the feed ports in order to perform simultaneously the radiation pattern and the impedance matching of all the radiating probes that form the array feed. The method is validated through a numerical design of an EBG antenna excited with four patch antennas. The structure is designed to radiate with a single lobe scanned at θ = 30∘ in the E‐plane. The interactions between each patch inside the EBG resonator are characterized with the CST MWS software. The optimum weights and the input impedances which simultaneously perform the objective radiation and the matching of all feeding ports are calculated by the developed global synthesis method. The feed network is designed with the Agilent ADS software in order to perform the specified weights and the impedances matching.
Role of Sexual Intercourse in Hematuria and Proteinuria in Males and Females
Authors: Hosseini Seyed Reza , Mohseni Mohammad Ghasem , Atharikia Davood
Published: October 2008

Objective: A probable association has been proposed between sexual intercourse and hematuria and proteinuria in either sex. The present study was to assess the role of sexual intercourse in hematuria and proteinuria in immediate dipstick urine test and morning urine sample analysis and whether sexual intercourse might be a cause of microscopic hematuria and proteinuria. Material and Methods: Forty-two healthy married adult volunteers (27 male and 15 female; age range 20–48) were enrolled in a prospective clinical trial. Immediately after sexual intercourse urine samples were analyzed regarding hematuria and proteinuria with a dipstick, and the next morning samples for standard urinalysis. For categorical data analysis Fisher’s exact test was utilized. p < 0.05 was considered significant. Results: Proteinuria immediately after intercourse was significantly higher in males (88.9 vs. 13.3%, p < 0.001) but females showed significant higher hematuria (73.3 vs. 22.2%). None of the women developed hematuria and/or proteinuria in morning after urinalysis samples but males indicated significant proteinuria (33.3 vs. 0%, p = 0.02). Conclusions: Proteinuria and hematuria following sexual intercourse are gender-dependent, and temporally related to the timing of the testing and sexual activity. Testing the urine in the morning following intercourse may give false-positive protein results in men, but there is no evidence of false-positive hematuria in women unless the activity immediately precedes the testing.
A Comparison of Kidney Retrieval Incisions in Laparoscopic Transperitoneal Donor Nephrectomy
Authors: Gupta Manu , Singh Pratipal , Dubey Deepak , Srivastava Aneesh , Kapoor Rakesh , Kumar Anant
Published: October 2008

Objective: To compare the modified iliac fossa and Pfannenstiel incisions for retrieving the kidney in laparoscopic transperitoneal donor nephrectomy. Patients and Methods: Two different incisions for retrieving the donor kidney were studied from January 2002 to December 2006. A total of 343 laparoscopic transperitoneal donor nephrectomies were performed. 110 kidneys were removed via our modified iliac fossa incision and 233 kidneys were retrieved using a Pfannenstiel incision. The warm ischemia time, analgesic requirement and hospital stay were compared. Other parameters studied were the length of incisions, total number of incisions (port and retrieval), and complications associated with them. Results: The warm ischemia time (3 vs. 3.5 min), mean hospital stay (3.35 vs. 3.8 days) and analgesic requirement were comparable. The mean length of incisions was 5.8 vs. 7.3 cm, respectively, and this difference was found to be statistically significant. The total number of incisions (port and retrieval) was 4 when the iliac fossa incision was used, whereas it was 5 when the kidney was retrieved using a Pfannenstiel incision. Two patients had bladder injury and 1 patient had bowel injury while making the Pfannenstiel incision. There was less morbidity associated with the iliac fossa incision. Conclusion: The iliac fossa incision had less morbidity whereas the Pfannenstiel incision scored in terms of cosmesis.
Protein Kinase A Type I and Type II Define Distinct Intracellular Signaling Compartments
Authors: Di Benedetto Giulietta , Zoccarato Anna , Lissandron Valentina , Terrin Anna , Li Xiang , Houslay Miles D. , Baillie George S. , Zaccolo Manuela
Published: October 2008

Protein kinase A (PKA) is a key regulatory enzyme that, on activation by cAMP, modulates a wide variety of cellular functions. PKA isoforms type I and type II possess different structural features and biochemical characteristics, resulting in nonredundant function. However, how different PKA isoforms expressed in the same cell manage to perform distinct functions on activation by the same soluble intracellular messenger, cAMP, remains to be established. Here, we provide a mechanism for the different function of PKA isoforms subsets in cardiac myocytes and demonstrate that PKA-RI and PKA-RII, by binding to AKAPs (A kinase anchoring proteins), are tethered to different subcellular locales, thus defining distinct intracellular signaling compartments. Within such compartments, PKA-RI and PKA-RII respond to distinct, spatially restricted cAMP signals generated in response to specific G protein–coupled receptor agonists and regulated by unique subsets of the cAMP degrading phosphodiesterases. The selective activation of individual PKA isoforms thus leads to phosphorylation of unique subsets of downstream targets.