bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of osmotic shrinkage on voltage-gated Ca2+ channel currents in rat anterior pituitary cells
Authors: Ben-Tabou De-Leon Shlomo , Ben-Zeev Galia , Nussinovitch Itzhak
Published: September 2005

Increased extracellular osmolarity ([Os]e) suppresses stimulated hormone secretion from anterior pituitary cells. Ca2+ influx may mediate this effect. We show that increase in [Os]e (by 18–125%) differentially suppresses L-type and T-type Ca2+ channel currents ( IL and IT, respectively); IL was more sensitive than IT. Hyperosmotic suppression of IL depended on the magnitude of increase in [Os]e and was correlated with the percent decrease in pituitary cell volume, suggesting that pituitary cell shrinkage can modulate L-type currents. The hyperosmotic suppression of IL and IT persisted after incubation of pituitary cells either with the actin-disrupter cytochalasin D or with the actin stabilizer phalloidin, suggesting that the actin cytoskeleton is not involved in this modulation. The hyperosmotic suppression of Ca2+ influx was not correlated with changes in reversal potential, membrane capacitance, and access resistance. Together, these results suggest that the hyperosmotic suppression of Ca2+ influx involves Ca2+ channel proteins. We therefore recorded the activity of L-type Ca2+ channels from cell-attached patches while exposing the cell outside the patch pipette to hyperosmotic media. Increased [Os]e reduced the activity of Ca2+ channels but did not change single-channel conductance. This hyperosmotic suppression of Ca2+ currents may therefore contribute to the previously reported hyperosmotic suppression of hormone secretion.
β-Adrenergic receptor-stimulated apoptosis in adult cardiac myocytes involves MMP-2-mediated disruption of β1 integrin signaling and mitochondrial pathway
Authors: Menon Bindu , Singh Mahipal , Ross Robert S. , Johnson Jennifer N. , Singh Krishna
Published: September 2005

Stimulation of β-adrenergic receptors (β-AR) induces apoptosis in adult rat ventricular myocytes (ARVMs) via the JNK-dependent activation of mitochondrial death pathway. Recently, we have shown that inhibition of matrix metalloproteinase-2 (MMP-2) inhibits β-AR-stimulated apoptosis and that the apoptotic effects of MMP-2 are possibly mediated via its interaction with β1 integrins. Herein we tested the hypothesis that MMP-2 impairs β1 integrin-mediated survival signals, such as activation of focal adhesion kinase (FAK), and activates the JNK-dependent mitochondrial death pathway. Inhibition of MMP-2 using SB3CT, a selective gelatinase inhibitor, significantly increased FAK phosphorylation (Tyr-397 and Tyr-576). TIMP-2, tissue inhibitor of MMP-2, produced a similar increase in FAK phosphorylation, whereas treatment of ARVMs with purified active MMP-2 significantly inhibited FAK phosphorylation. Inhibition of MMP-2 using SB3CT inhibited β-AR-stimulated activation of JNKs and levels of cytosolic cytochrome c. Treatment of ARVMs with purified MMP-2 increased cytosolic cytochrome c release. Furthermore, inhibition of MMP-2 using SB3CT and TIMP-2 attenuated β-AR-stimulated decreases in mitochondrial membrane potential. Overexpression of β1 integrins using adenoviruses expressing the human β1A-integrin decreased β-AR-stimulated cytochrome c release and apoptosis. Overexpression of β1 integrins also inhibited apoptosis induced by purified active MMP-2. These data suggest that MMP-2 interferes with the β1 integrin survival signals and activates JNK-dependent mitochondrial death pathway leading to apoptosis.
SNAT4 isoform of system A amino acid transporter is expressed in human placenta
Authors: Desforges M. , Lacey H. A. , Glazier J. D. , Greenwood S. L. , Mynett K. J. , Speake P. F. , Sibley C. P.
Published: September 2005

The system A amino acid transporter is encoded by three members of the Slc38 gene family, giving rise to three subtypes: Na+-coupled neutral amino acid transporter (SNAT)1, SNAT2, and SNAT4. SNAT2 is expressed ubiquitously in mammalian tissues; SNAT1 is predominantly expressed in heart, brain, and placenta; and SNAT4 is reported to be expressed solely by the liver. In the placenta, system A has an essential role in the supply of neutral amino acids needed for fetal growth. In the present study, we examined expression and localization of SNAT1, SNAT2, and SNAT4 in human placenta during gestation. Real-time quantitative PCR was used to examine steady-state levels of system A subtype mRNA in early (6–10 wk) and late (10–13 wk) first-trimester and full-term (38–40 wk) placentas. We detected mRNA for all three isoforms from early gestation onward. There were no differences in SNAT1 and SNAT2 mRNA expression with gestation. However, SNAT4 mRNA expression was significantly higher early in the first trimester compared with the full-term placenta ( P < 0.01). We next investigated SNAT4 protein expression in human placenta. In contrast to the observation for gene expression, Western blot analysis revealed that SNAT4 protein expression was significantly higher at term compared with the first trimester ( P < 0.05). Immunohistochemistry and Western blot analysis showed that SNAT4 is localized to the microvillous and basal plasma membranes of the syncytiotrophoblast, suggesting a role for this isoform of system A in amino acid transport across the placenta. This study therefore provides the first evidence of SNAT4 mRNA and protein expression in the human placenta, both at the first trimester and at full term.
Proton pump-rich cell secretes acid in skin of zebrafish larvae
Authors: Lin Li-Yih , Horng Jiun-Lin , Kunkel Joseph G. , Hwang Pung-Pung
Published: September 2005

The mammalian kidney excretes its metabolic acid load through the proton-transporting cells, intercalated cells, in the distal nephron and collecting duct. Fish excrete acid through external organs, gill, or skin; however, the cellular function is still controversial. In this study, molecular and electrophysiological approaches were used to identify a novel cell type secreting acid in skin of zebrafish ( Danio rerio) larvae. Among keratinocytes covering the larval surface, novel proton-secreting ionocytes, proton pump (H+-ATPase)-rich cells, were identified to generate strong outward H+ flux. The present work demonstrates for the first time, with a noninvasive technique, H+-secreting cells in an intact animal model, the zebrafish, showing it to be a suitable model in which to study the functions of vertebrate transporting epithelia in vivo.
Thrombin induces expression of FGF-2 via activation of PI3K-Akt-Fra-1 signaling axis leading to DNA synthesis and motility in vascular smooth muscle cells
Authors: Cao Huiqing , Dronadula Nagadhara , Rao Gadiparthi N.
Published: September 2005

To understand the mechanisms by which thrombin induces vascular smooth muscle cell (VSMC) DNA synthesis and motility, we have studied the role of phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR)-S6K1 signaling. Thrombin stimulated the phosphorylation of Akt and S6K1 in VSMC in a sustained manner. Blockade of PI3K-Akt-mTOR-S6K1 signaling by LY-294002, and rapamycin suppressed both thrombin-induced VSMC DNA synthesis and migration. Adenovirus-mediated expression of dominant-negative Akt also inhibited thrombin-induced VSMC DNA synthesis and migration. Furthermore, thrombin induced the expression of Fra-1 in a sustained PI3K-Akt-dependent and mTOR-independent manner in VSMC. Suppression of Fra-1 by its small interfering RNA attenuated both thrombin-induced VSMC DNA synthesis and migration. Thrombin also induced the expression of FGF-2 in a PI3K-Akt-Fra-1-dependent and mTOR-independent manner, and neutralizing anti-FGF-2 antibodies inhibited thrombin-stimulated VSMC DNA synthesis and motility. In addition, thrombin stimulated the tyrosine phosphorylation of EGF receptor (EGFR), and inhibition of its kinase activity significantly blocked Akt and S6K1 phosphorylation, Fra-1 and FGF-2 expression, DNA synthesis, and motility induced by thrombin in VSMC. Together these observations suggest that thrombin induces both VSMC DNA synthesis and motility via EGFR-dependent stimulation of PI3K/Akt signaling targeting in parallel the Fra-1-mediated FGF-2 expression and mTOR-S6K1 activation.
A probable role of dihydropyridine receptors in repression of Ca2+ sparks demonstrated in cultured mammalian muscle
Authors: Zhou Jingsong , Yi Jianxun , Royer Leandro , Launikonis Bradley S. , González Adom , García Jesús , Ríos Eduardo
Published: September 2005

To activate skeletal muscle contraction, action potentials must be sensed by dihydropyridine receptors (DHPRs) in the T tubule, which signal the Ca2+ release channels or ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR) to open. We demonstrate here an inhibitory effect of the T tubule on the production of sparks of Ca2+ release. Murine primary cultures were confocally imaged for Ca2+ detection and T tubule visualization. After 72 h of differentiation, T tubules extended from the periphery for less than one-third of the myotube radius. Spontaneous Ca2+ sparks were found away from the region of cells where tubules were found. Immunostaining showed RyR1 and RyR3 isoforms in all areas, implying inhibition of both isoforms by a T tubule component. To test for a role of DHPRs in this inhibition, we imaged myotubes from dysgenic mice ( mdg) that lack DHPRs. These exhibited T tubule development similar to that of normal myotubes, but produced few sparks, even in regions where tubules were absent. To increase spark frequency, a high-Ca2+ saline with 1 mM caffeine was used. Wild-type cells in this saline plus 50 μM nifedipine retained the topographic suppression pattern of sparks, but dysgenic cells in high-Ca2+ saline did not. Shifted excitation and emission ratios of indo-1 in the cytosol or mag-indo-1 in the SR were used to image [Ca2+] in these compartments. Under the conditions of interest, wild-type and mdg cells had similar levels of free [Ca2+] in cytosol and SR. These data suggest that DHPRs play a critical role in reducing the rate of spontaneous opening of Ca2+ release channels and/or their susceptibility to Ca2+-induced activation, thereby suppressing the production of Ca2+ sparks.
Nuclear targeting of stanniocalcin to mammary gland alveolar cells during pregnancy and lactation
Authors: Hasilo Craig P. , McCudden Christopher R. , Gillespie J. Ryan J. , James Kathi A. , Hirvi Edward R. , Zaidi Deenaz , Wagner Graham F.
Published: September 2005

In most mammalian tissues, the stanniocalcin-1 gene (STC-1) produces a 50-kDa polypeptide hormone known as STC50. Within the ovaries, however, the STC-1 gene generates three higher-molecular-mass variants known as big STC. Big STC is targeted locally to corpus luteal cells to block progesterone release. During pregnancy and lactation, however, ovarian big STC production increases markedly, and the hormone is released into the serum. During lactation, this increase in hormone production is dependent on a suckling stimulus, suggesting that ovarian big STC may have regulatory effects on the lactating mammary gland. In this report, we have addressed this possibility. Our results revealed that virgin mammary tissue contained large numbers of membrane- and mitochondrial-associated STC receptors. However, as pregnancy progressed into lactation, there was a decline in receptor densities on both organelles and a corresponding rise in nuclear receptor density, most of which were on milk-producing, alveolar cells. This was accompanied by nuclear sequestration of the ligand. Sequestered STC resolved as one ∼135-kDa band in the native state and therefore had the appearance of a big STC variant. However, chemical reduction collapsed this one band into six closely spaced, lower-molecular-mass species (28–41 kDa). Mammary gland STC production also underwent a dramatic shift during pregnancy and lactation. High levels of STC gene expression were observed in mammary tissue from virgin and pregnant rats. However, gene expression then fell to nearly undetectable levels during lactation, coinciding with the rise in nuclear targeting. These findings have thus shown that the mammary glands are indeed targeted by STC, even in the virgin state. They have further shown that there are marked changes in this targeting pathway during pregnancy and lactation, accompanied by a switch in ligand source (endogenous to exogenous). They also represent the first example of nuclear targeting by STC.
Susceptibility of the developing brain to acute hypoglycemia involving A1adenosine receptor activation
Authors: Kim Mina , Yu Zhao-Xue , Fredholm Bertil B. , Rivkees Scott A.
Published: September 2005

It has been suggested that the developing brain is less vulnerable to the adverse effects of hypoglycemia than the mature brain; however, this issue remains controversial. We also do not know the magnitude or duration of hypoglycemia needed to trigger hypoglycemic brain injury during development. To address this issue a series of in vivo and in vitro studies were performed. First, we established an acute model of insulin-induced hypoglycemia in mice by administering 3 U/kg of neutral-protamine Hagadorn insulin subcutaneously. When we examined degenerating neurons in hippocampus and striatum by TUNEL labeling, injury was observed after 4 h of hypoglycemia in postnatal day ( P)7 mice, and we observed more cell injury in animals rendered hypoglycemic at P 7 than at P21. Studies of hippocampal slice cultures revealed that reduction in glucose concentration induced more neuronal injury in slices prepared from P3 and P7 than from P14 and P21 mice. Treatment of slices with an adenosine A1receptor (A1AR) antagonist reduced the hypoglycemic damage, whereas agonists increased damage, particularly in slices prepared from very young pups. This suggests a critically important role for A1ARs, which was further demonstrated by the reduction of hypoglycemic damage in hippocampal slices prepared from A1AR−/−mice. Furthermore, insulin-induced hypoglycemia in P7 A1AR−/−mice did not increase TUNEL-positive cells, but a major increase was seen in A1AR+/−mice. These observations show that the developing nervous system is indeed sensitive to acute hypoglycemic injury and that A1AR activation contributes to damage induced by hypoglycemia, particularly in immature mouse brain.
Colonic fermentation from lactulose inhibits lipolysis in overweight subjects
Authors: Ferchaud-Roucher V. , Pouteau E. , Piloquet H. , Zaïr Y. , Krempf M.
Published: September 2005

One of the strategies to prevent insulin resistance is to reduce circulating free fatty acids (FFA). The aim of this study is to assess the effect of an oral lactulose load on fatty acid metabolism in overweight subjects. Eight overweight subjects received a primed constant intravenous infusion of [1-13C]acetate and of [1,1,2,3,3-2H5]glycerol for 9 h. After 3 h of tracer infusion, patients ingested 30 g lactulose, or saline solution. Arterialized blood samples were collected every 20 min. Basal plasma concentrations of acetate were similar before and between oral treatments as well as glycerol and FFA concentrations. Plasma acetate turnover was 11.4 ± 2.4 vs. 10.7 ± 1.4 μmol·kg−1·min−1[not significant (NS)], and plasma glycerol turnover was 3.8 ± 0.4 vs. 4.8 ± 1.9 μmol·kg−1·min−1(NS). After lactulose ingestion, acetate concentration increased twofold and then decreased to baseline. Acetate turnover rate increased to 15.5 ± 2.2 μmol·kg−1·min−1after lactulose treatment, whereas it was unchanged after saline treatment (10.3 ± 2.2 μmol·kg−1·min−1, P ≤ 0.0001). In contrast, FFA concentrations decreased significantly after lactulose ingestion and then increased slowly. Glycerol turnover decreased after lactulose ingestion compared with saline, 2.8 ± 0.4 vs. 3.5 ± 0.3 μmol·kg−1·min−1( P ≤ 0.05). A significant negative correlation was found between glycerol and acetate turnover after lactulose treatments ( r = −0.78, P ≤ 0.02). These results showed in overweight subjects a short-term decrease in FFA level and glycerol turnover after lactulose ingestion related to a decrease of lipolysis in close relationship with an increase of acetate production.
Heat stress increases apical glucose transport in the chicken jejunum
Authors: Garriga Carles , Hunter Richard R. , Amat Concepció , Planas Joana M. , Mitchell Malcolm A. , Moretó Miquel
Published: September 2005

In chickens, elevated environmental temperature reduces food intake. We have previously reported that, during heat stress, the intestinal mucosa has an increased capacity to take up sugars. To investigate whether the effects of warm environment on sugar uptake are an intestinal adaptation to lower energy intake or a response attributable to heat stress, we examined the glucose transport kinetics of apical and basolateral membranes of the jejunum and the mucosal morphology of broiler chickens maintained in climatic chambers for 2 wk. Experimental groups were 1) control ad libitum (CAL), fed ad libitum and in thermoneutral conditions (20°C); 2) heat stress ad libitum (HSAL), fed ad libitum and kept in a heated environment (30°C); and 3) control pair-fed (CPF), maintained in thermoneutral conditions and fed the same amount of food as that consumed by the HSAL group. Both the CPF and the HSAL groups showed reduced body weight gain, but only the HSAL chickens had lower plasma thyroid hormones and higher corticosterone than CAL and CPF groups. The fresh weight and length of the jejunum were only reduced in the HSAL group. The activity and expression of apical sodium-dependent glucose transporter 1 (SGLT-1) were increased by ∼50% in the HSAL chickens, without effects in the CPF group. No changes in Kd or in SGLT-1 and glucose transporter-2 Km were observed in the pair-fed and heated birds. These results support the view that increased intestinal hexose transport capacity is entirely dependent on adaptations of apical SGLT-1 expression to heat stress and is not due to reduced food intake.
Enhanced initial and sustained intake of sucrose solution in mice with an oxytocin gene deletion
Authors: Amico Janet A. , Vollmer Regis R. , Cai Hou-ming , Miedlar Julie A. , Rinaman Linda
Published: September 2005

Laboratory mice drink little sucrose solution on initial exposure, but later develop a strong preference for sucrose over water that plateaus after a few days. Both the initial neophobia and later plateau of sucrose intake may involve central oxytocin (OT) signaling pathways. If so, then mice that lack the gene for OT [OT knockout (KO)] should exhibit enhanced initial and sustained sucrose intake compared with wild-type (WT) cohorts. To test this hypothesis, female OT KO and WT mice (11–13 mo old) were given a two-bottle choice between 10% sucrose and water available ad libitum for 4 days. On the first day, sucrose intake was 20-fold greater in OT KO mice compared with WT cohorts. The avid sucrose consumption by OT KO mice increased further on day 2 and was sustained at significantly higher levels than intake by WT mice. Enhanced initial and sustained sucrose intake also was observed in 5- to 7-mo-old male OT KO mice. The effect of genotype was observed over a range of sucrose concentrations and was maintained over at least 8 days of continual exposure. However, there was no effect of genotype on daily intake of sucrose-enriched powdered chow. These findings indicate that the genetic absence of OT in mice is associated with enhanced initial and sustained intake of sucrose solutions. Thus central OT pathways may normally participate in limiting initial intake of novel ingesta and may also participate in limiting intake of sweet, highly palatable familiar ingesta.
Paradoxical redistribution of pulmonary blood flow in prone and supine humans exposed to hypergravity
Authors: Petersson Johan , Rohdin Malin , Sánchez-Crespo Alejandro , Nyrén Sven , Jacobsson Hans , Larsson Stig A. , Lindahl Sten G. E. , Linnarsson Dag , Glenny Robb W. , Mure Margareta
Published: September 2005

We hypothesized that exposure to hypergravity in the supine and prone postures causes a redistribution of pulmonary blood flow to dependent lung regions. Four normal subjects were exposed to hypergravity by use of a human centrifuge. Regional lung perfusion was estimated by single-photon-emission computed tomography (SPECT) after administration of 99mTc-labeled albumin macroaggregates during normal and three times normal gravity conditions in the supine and prone postures. All images were obtained during normal gravity. Exposure to hypergravity caused a redistribution of blood flow from dependent to nondependent lung regions in all subjects in both postures. We speculate that this unexpected and paradoxical redistribution is a consequence of airway closure in dependent lung regions causing alveolar hypoxia and hypoxic vasoconstriction. Alternatively, increased vascular resistance in dependent lung regions is caused by distortion of lung parenchyma. The redistribution of blood flow is likely to attenuate rather than contribute to the arterial desaturation caused by hypergravity.
Independent Controls of Attentional Influences in Primary and Secondary Somatosensory Cortex
Authors: Chapman C. Elaine , Meftah El-Mehdi
Published: September 2005

The neuronal mechanisms underlying enhanced perception of tactile stimuli with directed attention were investigated using single-unit recordings from primary (S1, n = 53) and secondary (S2, n = 50) somatosensory cortex in macaque monkeys. Neuronal responses to textures scanned under the digit tips (spatial periods, SP, of 2, 3.7 or 4.7 mm) were recorded while attention was directed either to discriminating a change in texture or to the reward and also in a neutral no-task condition. Cell discharge was quantified in three periods of the trials: salient Δ texture (directed attention), postreward, and static (both cases, attention directed to the reward). S1 texture- and non-texture-sensitive cells, as well as S2 non-texture-sensitive cells, showed a modest enhancement of discharge during the salient Δ texture period (∼25%) but no change in response gain, consistent with an additive increase in neuronal responsiveness with directed attention. In contrast, S2 texture-related cells showed a larger enhancement with directed attention to salient inputs (82%) and increased response gain, suggesting that directed attention produces a multiplicative increase in S2 responsiveness. During the postreward period, and also in no-task testing, S1 texture-sensitive cells preserved their sensitivity to SP. In contrast, S2 texture-, but not non-texture-, sensitive cells showed a marked suppression of discharge and decreased gain after the discrimination response. Together, the results support the notion that S2 discharge reflects stimulus parameters in relation to ongoing behavioral demands. The results also support the existence of two independent attentional mechanisms in somatosensory cortex, one generalized (S1 and S2), and the other focused on S2 texture-related cells.
Remapping Hand Movements in a Novel Geometrical Environment
Authors: Mosier Kristine M. , Scheidt Robert A. , Acosta Santiago , Mussa-Ivaldi Ferdinando A.
Published: September 2005

The issue of how the Euclidean properties of space are represented in the nervous system is a main focus in the study of visual perception, but is equally relevant to motor learning. The goal of our experiments was to investigate how the properties of space guide the remapping of motor coordination. Subjects wore an instrumented data glove that recorded the finger motions. Signals generated by the glove operated a remotely controlled endpoint: a cursor on a computer monitor. The subjects were instructed to execute movements of this endpoint with controlled motions of the fingers. This required inverting a highly redundant map from fingers to cursor motions. We found that 1) after training with visual feedback of the final error (but not of the ongoing cursor motion), subjects learned to map cursor locations into configurations of the fingers; 2) extended practice of movement led to more rectilinear cursor movement, a trend facilitated by training under continuous visual feedback of cursor motions; 3) with practice, subjects reduced motion in the degrees of freedom that did not contribute to the movements of the cursor; 4) with practice, subjects reduced variability of both cursor and hand movements; and 5) the reduction of errors and the increase in linearity generalized beyond the set of movements used for training. These findings suggest that subjects not only learned to produce novel coordinated movement to control the placement of the cursor, but they also developed a representation of the Euclidean space on which hand movements were remapped.
Impact of High-Frequency Stimulation Parameters on the Pattern of Discharge of Subthalamic Neurons
Authors: Garcia Liliana , D'Alessandro Giampaolo , Fernagut Pierre-Olivier , Bioulac Bernard , Hammond Constance
Published: September 2005

In clinical conditions, high-frequency stimulation (HFS) of subthalamic (STN) neurons in Parkinson's disease is empirically applied at ≥100 Hz (130–185 Hz), with pulses of short duration (60–100 μs) and 1- to 3-mA amplitude. Other parameter values produce no effect or aggravate the symptoms. To gain a better understanding of the mechanisms that underlie the therapeutic action of HFS, we have compared the effects of different combinations of parameter values delivered by clinical stimulators on the activity of STN neurons recorded in whole cell patch-clamp configuration in slices. We showed that none of tested combinations of parameters silenced the neurons. Non-therapeutic combinations i.e., low-frequency pulses (10–50 Hz), even at large amplitude or width, further excited the STN neurons with respect to their spontaneous activity. In contrast, combinations in the therapeutic range (80–185 Hz, 90–200 μs, 500–800 μA) replaced the preexisting activity by spikes, time-locked to the stimuli and thus presenting a striking regularity. When increasing pulse width or amplitude in this high-frequency range, the dual effect was still present but the activity generated became more irregular. We propose that during HFS at clinically relevant parameters, STN neurons behave as stable oscillators entirely driven by the stimulation, giving an average stable STN output that overrides spontaneous activity and introduces high-frequency regular spiking in the basal ganglia network.
Head Movement Evoked By Electrical Stimulation in the Supplementary Eye Field of the Rhesus Monkey
Authors: Chen L. Longtang , Walton Mark M. G.
Published: September 2005

Although the supplementary eye field (SEF) has been implicated in the control of head movements associated with gaze shifts, there is no direct evidence that SEF plays a role in the generation of head movements independent of gaze. If the SEF does, varying the duration of stimulation should selectively alter the head-movement kinematics during the postgaze-shift period. The duration of the stimulation was manipulated while head-unrestrained monkeys maintained stable head forward postures. The initial positions of the eyes in the orbits were systematically varied. Although combined movements of the eyes and head were produced in the majority of the trials, head movements were sometimes evoked in the absence of gaze shifts. These head-alone movements were most frequent when the initial eye position was contralateral to the stimulated side. When the stimulation produced eye and head movements, gaze onset was sometimes preceded by a relatively low-velocity phase of the head movement. Evoked head movements were primarily horizontal, unlike the gaze shifts, which typically had vertical components that varied according to the initial positions of the eyes in the orbits. The postgaze-shift head movements tended to be of low velocity and in many cases persisted until stimulation offset. In general, prolonging the stimulation resulted in improved centering of the eyes in the orbits. These findings suggest that, in addition to its previously described role in the generation of coordinated eye-head gaze shifts, the SEF is also involved in the control of head movements in the absence of a change of gaze.
Dopaminergic Modulation of Short-Term Synaptic Plasticity in Fast-Spiking Interneurons of Primate Dorsolateral Prefrontal Cortex
Authors: Gonzalez-Burgos G. , Kroener S. , Seamans J. K. , Lewis D. A. , Barrionuevo G.
Published: September 2005

Dopaminergic regulation of primate dorsolateral prefrontal cortex (PFC) activity is essential for cognitive functions such as working memory. However, the cellular mechanisms of dopamine neuromodulation in PFC are not well understood. We have studied the effects of dopamine receptor activation during persistent stimulation of excitatory inputs onto fast-spiking GABAergic interneurons in monkey PFC. Stimulation at 20 Hz induced short-term excitatory postsynaptic potential (EPSP) depression. The D1 receptor agonist SKF81297 (5 μM) significantly reduced the amplitude of the first EPSP but not of subsequent responses in EPSP trains, which still displayed significant depression. Dopamine (DA; 10 μM) effects were similar to those of SKF81297 and were abolished by the D1 antagonist SCH23390 (5 μM), indicating a D1 receptor-mediated effect. DA did not alter miniature excitatory postsynaptic currents, suggesting that its effects were activity dependent and presynaptic action potential dependent. In contrast to previous findings in pyramidal neurons, in fast-spiking cells, contribution of N-methyl-d-aspartate receptors to EPSPs at subthreshold potentials was not significant and fast-spiking cell depolarization decreased EPSP duration. In addition, DA had no significant effects on temporal summation. The selective decrease in the amplitude of the first EPSP in trains delivered every 10 s suggests that in fast-spiking neurons, DA reduces the amplitude of EPSPs evoked at low frequency but not of EPSPs evoked by repetitive stimulation. DA may therefore improve detection of EPSP bursts above background synaptic activity. EPSP bursts displaying short-term depression may transmit spike-timing-dependent temporal codes contained in presynaptic spike trains. Thus DA neuromodulation may increase the signal-to-noise ratio at fast-spiking cell inputs.
Presenilin 1 Deficiency Alters the Activity of Voltage-Gated Ca2+Channels in Cultured Cortical Neurons
Authors: Cook David G. , Li Xiaofan , Cherry Sheree D. , Cantrell Angela R.
Published: September 2005

Presenilins 1 and 2 (PS1 and PS2, respectively) play a critical role in mediating γ-secretase cleavage of the amyloid precursor protein (APP). Numerous mutations in the presenilins are known to cause early-onset familial Alzheimer's disease (FAD). In addition, it is well established that PS1 deficiency leads to altered intracellular Ca2+homeostasis involving endoplasmic reticulum Ca2+stores. However, there has been little evidence suggesting Ca2+signals from extracellular sources are influenced by PS1. Here we report that the Ca2+currents carried by voltage-dependent Ca2+channels are increased in PS1-deficient cortical neurons. This increase is mediated by a significant increase in the contributions of L- and P-type Ca2+channels to the total voltage-mediated Ca2+conductance in PS1 (−/−) neurons. In addition, chelating intracellular Ca2+with 1,2-bis-( o-aminophenoxy)ethane- N,N,N′,N′-tetraacetic acid (BAPTA) produced an increase in Ca2+current amplitude that was comparable to the increase caused by PS1 deficiency. In contrast to this, BAPTA had no effect on voltage-dependent Ca2+conductances in PS1-deficient neurons. These data suggest that PS1 deficiency may influence voltage-gated Ca2+channel function by means that involve intracellular Ca2+signaling. These findings reveal that PS1 functions at multiple levels to regulate and stabilize intracellular Ca2+levels that ultimately control neuronal firing behavior and influence synaptic transmission.
The Federal Structure of a Republic of Reasons
Authors: King Loren A.
Published: September 2005

Following Rawls, many political liberals hold reasonableness in high regard. Reasonable citizens can disagree, however, and some may find their arguments routinely ignored in elections and legislatures. Should we be troubled by such failures of institutional responsiveness as a matter of justice? The author argues that the expectation of such failures would lead parties in an original position to favor certain classes of institutions over others: A Theory of Justice and Political Liberalism together suggest a particular federal structure to a republic of reasons.
Kantian Personal Autonomy
Authors: Taylor Robert S.
Published: September 2005

Jeremy Waldron has recently raised the question of whether there is anything approximating the creative self-authorship of personal autonomy in the writings of Immanuel Kant. After considering the possibility that Kantian prudential reasoning might serve as a conception of personal autonomy, I argue that the elements of a more suitable conception can be found in Kant’s Tugendlehre, or “Doctrine of Virtue”—specifically, in the imperfect duties of self-perfection and the practical love of others. This discovery is important for at least three reasons: first, it elucidates the relationship among the various conceptions of autonomy employed by personal-autonomy theorists and contemporary Kantians; second, it brings to the surface previously unnoticed or undernoticed features of Kant’s moral theory; and third, it provides an essential line of defense against certain critiques of contemporary Kantian theories, especially that of John Rawls.
Large Brains in Autism: The Challenge of Pervasive Abnormality
Authors: Herbert Martha R.
Published: September 2005

The most replicated finding in autism neuroanatomy—a tendency to unusually large brains—has seemed paradoxical in relation to the specificity of the abnormalities in three behavioral domains that define autism. We now know a range of things about this phenomenon, including that brains in autism have a growth spurt shortly after birth and then slow in growth a few short years afterward, that only younger but not older brains are larger in autism than in controls, that white matter contributes disproportionately to this volume increase and in a nonuniform pattern suggesting postnatal pathology, that functional connectivity among regions of autistic brains is diminished, and that neuroinflammation (including microgliosis and astrogliosis) appears to be present in autistic brain tissue from childhood through adulthood. Alongside these pervasive brain tissue and functional abnormalities, there have arisen theories of pervasive or widespread neural information processing or signal coordination abnormalities (such as weak central coherence, impaired complex processing, and underconnectivity), which are argued to underlie the specific observable behavioral features of autism. This convergence of findings and models suggests that a systems- and chronic disease-based reformulation of function and pathophysiology in autism needs to be considered, and it opens the possibility for new treatment targets.
Creative Requirement
Authors: Unsworth Kerrie L. , Wall Toby D. , Carter Angela
Published: September 2005

We identify the creative requirement of a job as a neglected predictor of employee creativity and propose that it may account for relationships between traditional work factors and creativity. As such, it may represent a more effective means of increasing creativity than changes in job design. Using structural equation modeling, we tested this model against four competing models using a sample of 1,083 health service employees. Creative requirement was found to account for much of the variance by fully mediating the effects of supportive leadership and role requirements and partially mediating those of empowerment and time demands. We conclude that creative requirement is an important proximal determinant of employee creativity and a potentially significant intervention.
Antecedents and Performance Consequences of Helping Behavior in Work Groups
Authors: Ng K. Yee , Van Dyne Linn
Published: September 2005

Our study examines two models of helping behavior in work groups. Our first model is a cross-level model and predicts that group-level cohesion, cooperative norms, and task conflict are related to individual helping behavior (peer-rated). Results support our hypotheses and further demonstrate that of the three group characteristics, cooperative norms have the strongest relationship with individual helping behavior. Our second model is a group-level model and examines the relationships among configural conceptualizations of group-level helping and group performance in conjunctive tasks. Results demonstrate that the least and the most helpful members in the group influence group performance in interesting ways. We conclude by discussing implications of our findings for practice and future research.
Service Leader Interaction Behaviors
Authors: Testa Mark R. , Ehrhart Mark G.
Published: September 2005

A key dynamic in satisfying customers is effective leadership of customer contact employees. In spite of decades of leadership study, little research has investigated effective leadership interaction behaviors specific to the service environment. The purpose of this investigation is to compare positive and negative interaction behaviors as reported by both managers and employees. Using the Critical Incident Technique (CIT), 305 positive and 234 negative incidents of service leader interaction behavior were collected from 120 managers and 231 employees drawn from73 service organizations. Using Yukl’s (2002) framework of leadership behaviors, the incidents were categorized to identify the most relevant behaviors for the service environment. The findings revealed 14 positive and 16 negative specific subcategories of interaction behavior, with significant disparities in perceptions between employees and managers. The implications of these findings are discussed and hypotheses are provided to guide future inquiry.
Reactive Astrocytes in Neural Repair and Protection
Authors: Sofroniew Michael V.
Published: September 2005

Reactive astrocytosis occurs prominently in response to all forms of CNS injury or disease. The functions of reactive astrocytes are not well understood, and both harmful and beneficial activities have been attributed to these cells. The basic process of reactive astrocytosis is conserved in vertebrate evolution, suggesting fitness-enhancing benefits, but scar-forming reactive astrocytes are often regarded as uniformly detrimental to clinical outcome, in particular, when implicated as inhibitors of axon regeneration. Transgenic mouse models are providing new means to study the activities of reactive astrocytes after CNS insults in vivo. Recent studies point toward roles for reactive astrocytes in restricting inflammation and protecting neurons and oligodendrocytes, thereby helping to limit tissue degeneration and preserve function after CNS injury.
Neurogenesis in the Adult Ischemic Brain: Generation, Migration, Survival, and Restorative Therapy
Authors: Zhang Rui Lan , Zhang Zheng Gang , Chopp Michael
Published: September 2005

This article reviews current data on the induction of neurogenesis after stroke in the adult brain. The discussion of neurogenesis is divided into production, migration, and survival of these newly formed cells. For production, the subpopulations and the types of cell division are presented. Discussion of cell migration entails presenting data on both the pathways as well as the molecular targeting of newly formed neural progenitor cells to sites of injury. The role of the vascular and the astrocytic microenvironment in promoting the survival and integration of progenitor cells is also presented. Cell-based and pharmacological therapies designed to restore neurological function that promote neurogenesis are described. These therapies also induce angiogenesis and astrocytic changes that brain tissue, which prime the ischemic brain to foster the survival of the newly formed progenitor cells. Signaling pathways that regulate neurogenesis and angiogenesis are also addressed. This review summarizes recent data on neurogenesis and provides insight into the potential for restorative treatments of stroke.
Targeting Prefrontal Cortical Dopamine D1 and N-Methyl-D-Aspartate Receptor Interactions in Schizophrenia Treatment
Authors: Yang Charles R. , Chen Long
Published: September 2005

The prefrontal cortex plays a principal role in higher cognition and particularly in the fast online manipulation of appropriate information to guide forthcoming behavior. Dysfunction of this process represents a main feature in the pathophysiology of schizophrenia. Both dopamine D1 and N-methyl-D-aspartate (NMDA) receptors in the prefrontal cortex play a critical role in synaptic plasticity, memory mechanisms, and cognition. Recent data have shown that D1 and NMDA receptors interact bidirectionally and may greatly influence the output of the prefrontal cortex. Hypofunction of these receptor systems in the prefrontal cortex is found in schizophrenia. This review attempts to summarize some of the latest findings on the cellular mechanisms that underlie D1-NMDA receptor interactions. These findings have provided potential therapeutic strategies that aim to functionally up-regulate D1 and/or NMDA receptor safely via selective activation of D1 receptors or coagonist activation of NMDA receptors through blockade of the glycine transporter-1.
Conceptual Framework and Statistical Procedures for Delineating and Testing Multilevel Theories of Homology
Authors: Chen Gilad , Bliese Paul D. , Mathieu John E.
Published: September 2005

Scholars have been interested in the extent to which organizational phenomena generalize across levels of analysis for quite some time. However, theoretical frameworks for developing homologous multilevel theories (i.e., theories involving parallel relationships between parallel constructs at different levels of analysis) have yet to be developed, and current analytical tools for testing such theories and models are limited and inflexible. In this article, the authors first propose a typology of multilevel theories of homology that considers different stages of theory development and different levels of similarity in relationships across levels. Building on cross-validation principles, the authors then delineate and demonstrate a comprehensive and flexible statistical procedure for testing different multilevel theories of homology. Finally, the authors discuss implications for theory, research, and practice, as well as potential caveats of the new statistical tests.
Bootstrapped Confidence Intervals as an Approach to Statistical Inference
Authors: Wood Michael
Published: September 2005

Confidence intervals are in many ways a more satisfactory basis for statistical inference than hypothesis tests. This article explains a simple method for using bootstrap resampling to derive confidence intervals. This method can be used for a wide variety of statistics—including the mean and median, the difference of two means or proportions, and correlation and regression coefficients. It can be implemented by an Excel spreadsheet, which is available to readers on the Web. The rationale behind the method is transparent, and it relies on almost no sophisticated statistical concepts.
Auditing Information Structures in Organizations: A Review of Data Collection Techniques for Network Analysis
Authors: Zwijze-Koning Karen H. , de Jong Menno D. T.
Published: September 2005

Network analysis is one of the current techniques for investigating organizational communication. Despite the amount of how-to literature about using network analysis to assess information flows and relationships in organizations, little is known about the methodological strengths and weaknesses of the underlying data collection techniques. This article reviews the methodological literature on methods that may be used for network analysis. For each technique, reliability and validity issues are discussed, as well as the applicability for organizational research questions.
Mendez v. Westminster School District: How It Affected Brown v. Board of Education
Authors: Aguirre Frederick P.
Published: September 2005

Most Americans are keenly aware of the African American civil rights movement. However, few know about the comparable struggle of Mexican Americans to enjoin the practice of segregated public schools in the Southwest. This article analyzes Mendez v. Westminster School District, a 1946 federal court case that ruled that separate but equal schools for Mexican American children in Orange County, California, was unconstitutional and that influenced the famous 1954 case of Brown v. Board of Education.
Juárez: The Reflection of U.S. Values in a Historical Drama
Authors: Dittloff Scott
Published: September 2005

This article is designed to survey mid-20th century American perceptions of Latin America through popular culture. It focuses on an analysis of the motion picture treatment of Latin America in the American film Juárez. The plot, characters, and cinematography have all been influenced by the social and political climate in the United States and Latin America and by relations between the two regions. The movie reflects the sociopolitical culture of the United States (where the movie was made) at that time.
Ethnicity and Gender Influences on Learning Styles in Nursing Students From an Hispanic-Serving Institution
Authors: Sizemore Mary Hoyte , Schultz Pamela N.
Published: September 2005

Literature has shown that considerations of learning styles are important in the educational process of health professionals. Among other variables, differences of learning styles may be influenced by language, culture, and heritage. The purpose of this study was to describe the learning styles of nursing students at an Hispanic-serving university. This study discusses the influence of gender and ethnicity on learning styles and the role of academic acculturation in nursing education.
Dialoguing the Latina Experience in Higher Education
Authors: Reyes Xaé Alicia , Ríos Diana I.
Published: September 2005

In this article, the authors discuss experiences and processes in their professional development as Latina academics. They frame their dialogue chronologically around the following themes: family background, graduate school, experiences with colleagues, participation in academia, interactions with students, and situations that inspire and motivate. By sharing their perspectives on issues linked to their status as women of color, the authors construct meaning and identify potential strategies for recruitment and success of minority students and academics.
Characterisation of nickel based hardfacing deposits on austenitic stainless steel
Authors: Das C. R. , Albert S. K. , Bhaduri A. K. , Sudha C. , Terrance A. L. E.
Published: September 2005

Nickel based hardfacing alloys Colmonoy-5 and Colmonoy-6 deposited on type 316L austenitic stainless steel substrate using the gas tungsten arc welding process, were characterised for their microstructure and hardness variations across the deposit/substrate interface, and for identification of the principal precipitates present in these hardface deposits. Hardness measurements and electron probe microanalysis (EPMA) across the interface revealed the presence of a dilution zone 2·5 mm wide in the Colmonoy-6 deposit and 1·5 mm wide in the Colmonoy-5 deposit. EPMA and X-ray diffraction studies of the precipitates showed that he blocky type precipitates were chromium borides and the needle-like precipitates were chromium carbides. Also, stress relief heat treatment at 1123 K for 4 h was found to have no significant effect on the hardness of these hard face deposits.