bluuebunny/crossref_metadata_2025 huggingface dataset:
ROLE OF p38‐MITOGEN‐ACTIVATED PROTEIN KINASE IN ISCHAEMIC PRECONDITIONING IN RAT HEART
Authors: Bell James R , Eaton Philip , Shattock Michael J
Published: September 2007

Activation of p38‐mitogen‐activated protein kinase (MAPK) has been implicated in the signalling cascade leading to protection by ischaemic preconditioning. This, however, is controversial and there is a plethora of conflicting data in the literature. Although many experimental differences may contribute to this, two in particular may be confounding: (i) the failure to account for p38‐MAPK activation during aerobic perfusion; and (ii) the use of the anti‐oxidant dimethylsulphoxide (DMSO) as the vehicle for the commonly used p38‐MAPK inhibitor SB203580. We have investigated the effects of aerobic perfusion, ischaemia and preconditioning on p38‐MAPK activation. In addition, we have used water‐soluble SB203580 hydrochloride (SB203580.HCl) and DMSO to probe the role of p38‐MAPK in preconditioning and ischaemic injury.

Activation of p38‐MAPK in rat isolated hearts was assessed using a dual phosphospecific antibody during cannulation, aerobic perfusion and index, autolytic and preconditioned ischaemia. The effect of SB203580.HCl (10 mmol/L) in ischaemic preconditioning and ischaemia/reperfusion was tested using recovery of function and tetrazolium (TTC) staining as end‐points.

Aerobic perfusion induced rapid activation (34% of maximal ischaemia‐induced increase; P < 0.05) of p38‐MAPK after 2 min that returned to baseline after 30 min. Index, autolytic and preconditioned ischaemia activated p38‐MAPK, with index ischaemia peaking after 15 min (520% of basal; P < 0.05) before declining. SB203580.HCl blocked p38‐MAPK activity, but did not block ischaemic preconditioning when bracketing the trigger phase and was not protective when given during ischaemia.

In the rat isolated heart, activation of p38‐MAPK is neither a unique feature of preconditioning nor a prerequisite. Previous studies using SB203580 may have been complicated by failure to account for the activation of p38‐MAPK by the protocol itself and the anti‐oxidant properties of the most commonly used vehicle DMSO.
REGULATION OF ENDOTHELIAL NITRIC OXIDE SYNTHASE: INVOLVEMENT OF PROTEIN KINASE G 1β, SERINE 116 PHOSPHORYLATION AND LIPID STRUCTURES
Authors: John Theresa A , Ibe Basil O , Raj J Usha
Published: September 2007

Endothelial nitric oxide synthase (NOS3) is important for vascular homeostasis. The role of protein kinase G (PKG) in regulation of NOS3 activity was studied in primary cultures of newborn lamb lung microvascular endothelial cells (LMVEC).

We determined the presence of PKG in fetal and neonatal LMVEC as well as subcellular localization of PKG isoforms in the neonatal cells by fluorescence immunohistochemistry. We used diaminofluorescein (DAF) fluorophore to measure nitric oxide (NO) production from neonatal LMVEC. We confirmed that NO measured was from constitutive NOS3 by inhibiting it with NOS inhibitors.

To identify a role for PKG in basal NO production, we measured NO release from LMVEC cells using 4‐amino‐5‐methylamino‐2′,7′‐difluorofluorescein (DAF‐FM; 0.5–0.8 µmol/L) with and without prior stimulation with the PKG activator 8‐bromo‐cGMP (8‐Br‐cGMP; 0.3 and 3 µmol/L) or prior PKG inhibition with β‐phenyl‐1,N2‐etheno‐8‐bromoguanosine‐3′,5′‐cyclic monophosphorothionate (BPC; 0.3 and 3 µmol/L). With the same drugs, we determined the role of PKG on cellular expression of NOS3 and serine 116 phosphorylated NOS (pSer116‐NOS) by qualitative and quantitative immunofluorescence assays, as well as western blotting.

Because PKG 1β was distributed throughout the cytosol in a punctate expression, we used 2 mmol/L cyclodextrin, a cholesterol extractor, to determine a role for lipid vesicles in PKG regulation of NO production.

Protein kinase G 1β gave a punctate appearance, indicating its presence in intracellular vesicles. Nitric oxide production decreased by approximately 20% with 300 nmol/L and 3 µmol/L 8‐Br cGMP (P < 0.05) and increased by 20.8 ± 3.7% with 3 µmol/L BPC (P < 0.001), indicating that both stimulated and basal PKG activity has inhibitory effects on basal NOS3 function. Nitric oxide synthase immunofluorescence and immunoblot expression were decreased and pSer116‐NOS immunofluorescence was increased by 800 nmol/L 8‐Br‐cGMP and 170 µmol/L (Z)‐1‐[2‐(2‐aminoethyl)‐N‐(2‐ammonio‐ethyl)amino]diazen‐1‐ium‐1, 2‐diolate (DETANONOate). The effect of cyclodextrin indicated that cholesterol extraction interfered with PKG inhibition of NOS. Further examination of pSer116‐NOS by immunohistochemistry showed it abundant in the endoplasmic reticulum and colocalized with PKG 1β, especially in nuclear vesicles.

We conclude that endothelial PKG is involved in endogenous regulation of basal NOS3 activity with the involvement of lipid structures, the endoplasmic reticulum and the nucleus. Protein kinase G 1β is colocalized with pSer116‐NOS, indicating that PKG action may involve serine 116 phosphorylation on NOS.
INFLUENCE OF SALT ON SUBCELLULAR LOCALIZATION OF NITRIC OXIDE SYNTHASE ACTIVITY AND EXPRESSION IN THE RENAL INNER MEDULLA
Authors: Sullivan Jennifer C , Smart Eric J , Pollock David M , Pollock Jennifer S
Published: September 2007

The aims of this study were: (i) to characterize the subcellular localization of nitric oxide synthase (NOS) 1 and NOS3 activity and expression within the cytosolic, plasma membrane and intracellular membrane subcellular fractions of the renal inner medulla of rats; and (ii) to determine whether NOS1 and NOS3 activity and expression in subcellular fractions of the renal inner medulla are regulated by dietary salt intake. Although the NOS system is important in maintaining Na+and water homeostasis, the identity of the NOS isoform that is sensitive to dietary Na+remains unclear. In addition, subcellular localization of both NOS1 and NOS3 has been shown to regulate enzymatic activity and influence the ability of NOS to produce nitric oxide (NO).

Renal inner medullae were dissected from male Sprague‐Dawley rats and separated into cytosolic, plasma membrane and intracellular membrane fractions for measurement of NOS activity and western blot analysis.

On a normal‐salt diet, NOS activity and NOS1 and NOS3 protein expression were present in all three subcellular fractions, although total NOS activity was enriched in the intracellular membrane fraction. In response to a high‐salt diet, urinary nitrate/nitrite (NOx) increased. Despite an increase in NOxexcretion, total NOS activity in the renal inner medullary homogenate was decreased. There were no detectable differences in NOS activity in the subcellular fractions. Expression of NOS1 protein was decreased in the cytoplasmic and plasma membrane fractions, although maintained in the intracellular membrane fraction, in response to high salt. Expression of NOS3 protein was unaffected by high salt.

In conclusion, we hypothesize that NOS1 localization in the intracellular membrane is important in increasing NO production to aid Na+and water homeostasis.
RAPID EFFECT OF PROGESTERONE ON TRANSEPITHELIAL RESISTANCE OF HUMAN FETAL MEMBRANES: EVIDENCE FOR NON‐GENOMIC ACTION
Authors: Verikouki CH , Hatzoglou CH , Gourgoulianis KI , Molyvdas PA , Kallitsaris A , Messinis IE
Published: September 2007

The factors that regulate human fetal membrane transport mechanisms are unknown. The aim of the present study was to investigate the effect of progesterone on transepithelial electrical resistance (RTE) in the human amniochorion.

Fetal membranes from uncomplicated term pregnancies were obtained immediately after vaginal or Caesarean deliveries. Intact pieces were mounted as planar sheets separating an Ussing chamber. Progesterone (10−4 to 10−7 mol/L), mifepristone (10−4 to 10−8 mol/L) and combinations of progesterone plus mifepristone were applied to the chambers facing the fetal or maternal sides of the membrane. The RTE was measured before and 1, 5, 10, 15, 20, 25, 30, 45 and 60 min after each solution was added (at 37°C). The RTE was calculated in Ω.cm2, according to Ohm's law.

The mean (±SEM) basal value of RTE before the application of any substance in all experiments was 29.1 ± 0.4 Ω.cm2.  The net change in the RTE (ΔRTE) in relation to the basal value was calculated in each experiment. Progesterone, mifepristone and the combination of progesterone and mifepristone induced a rapid, surge‐type increase in RTE during the 1st min on both sides of the membrane. The combination of progesterone plus mifepristone exerted a synergistic action. The effect was stronger on the fetal side than on the maternal side for all substances tested (P < 0.05). The highest ΔRTE during the 1st min on the fetal side was seen with the combination of progesterone plus mifepristone (4.0 ± 0.3 Ω.cm2) and the lowest ΔRTE occurred with mifepristone (1.5 ± 0.1 Ω.cm2).

The present results demonstrated that the RTE of human fetal membranes increases rapidly in response to progesterone. It is possible that changes in RTE play a role in the control of membrane permeability during pregnancy.
FUNCTIONAL INTERACTION BETWEEN DPI 201‐106, A DRUG THAT MIMICS CONGENITAL LONG QT SYNDROME, AND SEVOFLURANE ON THE GUINEA‐PIG CARDIAC ACTION POTENTIAL
Authors: Kang Jiesheng , Chen Xiao‐Liang , Reynolds William P , Rampe David
Published: September 2007

Sevoflurane produces QT prolongation on the electrocardiogram, predominantly via inhibition of the slow delayed rectifier K+ current. DPI 201‐106 is an experimental drug that produces QT prolongation by reducing Na+ channel inactivation, thereby mimicking congenital long QT syndrome type 3 (LQT3). The present study explores the electrophysiological consequences of administration of sevoflurane in the presence of impaired Na+ channel activity.

We examined the effects of sevoflurane and DPI 201‐106, alone and in combination, on the cardiac action potential of guinea‐pig ventricular myocytes using standard microelectrode techniques.

Both sevoflurane and DPI‐201‐106 prolonged action potential duration, with the combination of the two drugs producing greater than additive effects. Similarly, instability and triangulation of the action potential waveform, measures of pro‐arrhythmia, were more pronounced when both drugs were combined.

Sevoflurane treatment significantly alters cardiac action potential waveforms when administered in the presence of impaired Na+ channel inactivation. These results indicate the potential for ventricular arrhythmia when sevoflurane is administered to LQT3 patients and suggests caution when using sevoflurane in this population.
Unbiased cell quantification reveals a continued increase in the number of neocortical neurones during early post‐natal development in mice
Authors: Lyck Lise , Krøigård Thomas , Finsen Bente
Published: September 2007

The post‐natal growth spurt of the mammalian neocortex has been attributed to maturation of dendritic arborizations, growth and myelination of axons, and addition of glia. It is unclear whether this growth may also involve recruitment of additional neurones. Using stereological methods, we analysed the number of neurones and glia in the neocortex during post‐natal development in two separate strains of mice. Cell counting by the optical fractionator revealed that the number of neurones increased 80–100% from the time of birth to post‐natal day (P)16, followed by a reduction by approximately 25% in the young adult mouse at P50–55. Unexpectedly, at the time of birth less than half of the neurones and at P8 only 65% of the neurones expressed neuronal nuclear antigen (NeuN), a marker of mature post‐migratory neurones. In accordance with these observations, NeuN acquisition by neurones in layer VIa was delayed until P16. The number of glia reached its maximum at P16, whereas the number of oligodendroglia, identified using a transgenic marker, increased until P55, the latest time of observation. Neurones continued to accumulate in the developing neocortex during the first 2 weeks of post‐natal development, underscoring fundamental differences in brain development in the mouse compared with human and non‐human primates. Further, delayed acquisition of NeuN by neurones in the deepest neocortical layers and continued addition of oligodendroglia to the neocortex suggested that neocortical maturation should be regarded as an ongoing process continuing into the young adult mouse.
Directional responses of visual wulst neurones to grating and plaid patterns in the awake owl
Authors: Baron Jerome , Pinto Lucas , Dias Marcelo Oliveira , Lima Bruss , Neuenschwander Sergio
Published: September 2007

The avian retinothalamofugal pathway reaches the telencephalon in an area known as visual wulst. A close functional analogy between this area and the early visual cortex of mammals has been established in owls. The goal of the present study was to assess quantitatively the directional selectivity and motion integration capability of visual wulst neurones, aspects that have not been previously investigated. We recorded extracellularly from a total of 101 cells in awake burrowing owls. From this sample, 88% of the units exhibited modulated directional responses to sinusoidal gratings, with a mean direction index of 0.74 ± 0.03 and tuning bandwidth of 28 ± 1.16°. A direction index higher than 0.5 was observed in 66% of the cells, thereby qualifying them as direction selective. Motion integration was tested with moving plaids, made by adding two sinusoidal gratings of different orientations. We found that 80% of direction‐selective cells responded optimally to the motion direction of the component gratings, whereas none responded to the global motion of plaids, whose direction was intermediate to that of the gratings. The remaining 20% were unclassifiable. The strength of component motion selectivity rapidly increased over a 200 ms period following stimulus onset, maintaining a relatively sustained profile thereafter. Overall, our data suggest that, as in the mammalian primary visual cortex, the visual wulst neurones of owls signal the local orientated features of a moving object. How and where these potentially ambiguous signals are integrated in the owl brain might be important for understanding the mechanisms underlying global motion perception.
Detecting modulated signals in modulated noise: (II) neural thresholds in the songbird forebrain
Authors: Bee Mark A. , Buschermöhle Michael , Klump Georg M.
Published: September 2007

Sounds in the real world fluctuate in amplitude. The vertebrate auditory system exploits patterns of amplitude fluctuations to improve signal detection in noise. One experimental paradigm demonstrating these general effects has been used in psychophysical studies of ‘comodulation detection difference’ (CDD). The CDD effect refers to the fact that thresholds for detecting a modulated, narrowband noise signal are lower when the envelopes of flanking bands of modulated noise are comodulated with each other, but fluctuate independently of the signal compared with conditions in which the envelopes of the signal and flanking bands are all comodulated. Here, we report results from a study of the neural correlates of CDD in European starlings (Sturnus vulgaris). We manipulated: (i) the envelope correlations between a narrowband noise signal and a masker comprised of six flanking bands of noise; (ii) the signal onset delay relative to masker onset; (iii) signal duration; and (iv) masker spectrum level. Masked detection thresholds were determined from neural responses using signal detection theory. Across conditions, the magnitude of neural CDD ranged between 2 and 8 dB, which is similar to that reported in a companion psychophysical study of starlings [U. Langemann & G.M. Klump (2007) Eur. J. Neurosci., 26, 1969–1978]. We found little evidence to suggest that neural CDD resulted from the across‐channel processing of auditory grouping cues related to common envelope fluctuations and synchronous onsets between the signal and flanking bands. We discuss a within‐channel model of peripheral processing that explains many of our results.
Overexpression of APP provides neuroprotection in the absence of functional benefit following middle cerebral artery occlusion in rats
Authors: Clarke Jared , Thornell Anders , Corbett Dale , Soininen Hilkka , Hiltunen Mikko , Jolkkonen Jukka
Published: September 2007

Cerebral ischaemia leads to a transient accumulation of β‐amyloid precursor protein (APP) and β‐amyloid (Aβ) peptides adjacent to the ischaemic lesion. There is conflicting evidence that APP/Aβ fragments may either enhance neuronal plasticity or be neurotoxic. The aim of the current study was to assess the effect of overexpression of human APP in rats on functional recovery following cerebral ischaemia. Adult APP‐overexpressing (hAPP695 Tg) rats subjected to transient middle cerebral artery occlusion (MCAO) had significantly smaller infarct volumes than non‐transgenic littermates, yet did not perform better on a series of sensorimotor or learning tests during a 6‐month follow‐up period. In fact, transgenic animals were found to be significantly more impaired in both the beam‐walking and Morris water maze tests following MCAO. Immunohistochemistry showed human Aβ‐positive staining in the cortex and hippocampus of APP transgenic rats. The present data suggest that while overexpression of APP in rats may provide some histological neuroprotection in the event of cerebral ischaemia, this does not translate into significant functional recovery.
Group S8A serine proteases, including a novel enzyme cadeprin, induce long‐lasting, metabotropic glutamate receptor‐dependent synaptic depression in rat hippocampal slices
Authors: MacGregor Duncan G. , Mallon Andrew P. , Harvey Alan. L. , Young Louise , Nimmo Hugh G. , Stone Trevor W.
Published: September 2007

Long‐term potentiation and long‐term depression (LTD) are forms of synaptic plasticity in the central nervous system. We now report that a group of chymotrypsin‐like serine proteases, especially members of the S8A subfamily, induce LTD of evoked potentials in rat hippocampal slices. The proteolytic activity of these enzymes is required for the induction of LTD, as serine protease inhibitors prevent the effect. The depression is partly mediated by the suppression of transmitter release from glutamatergic terminals but also involves an elevation of action potential threshold with no change of post‐synaptic membrane potential or input resistance. We have also isolated a novel and more potent related enzyme, cadeprin, fromAspergillus. The LTD produced by all of these proteases is not dependent on receptors for several transmitter systems, includingN‐methyl‐d‐aspartate or adenosine receptors, but is prevented by blocking group I metabotropic glutamate receptors. The activity of cadeprin, subtilisin and other S8A serine proteases may shed light on the mechanisms of LTD and a related endogenous molecule could have a physiological or pathological role as a modulator of synaptic plasticity in the mammalian hippocampus.
Synchronous oscillations and phase reorganization in the basal ganglia during akinesia induced by high‐dose haloperidol
Authors: Burkhardt John M. , Constantinidis Christos , Anstrom Kristin K. , Roberts David C. S. , Woodward Donald J.
Published: September 2007

Movement disorders such as tremor and akinesia observed in Parkinson's disease have been attributed to dopamine (DA) depletion in the basal ganglia. The changes in subcortical neuronal discharge patterns that follow DA depletion have been a matter of much discussion. Here, we implanted rats with chronic recording electrodes bilaterally in the striatum (CPu) and external globus pallidus (GPe), and induced both acute and repeated DA blockade by administration of high‐dose haloperidol. Recordings were made in baseline states, as well as before and after haloperidol injections, which rendered rats akinetic. The immediate physiological effect of pharmacological DA blockade was the development of prominent oscillatory firing in the 6–8 Hz range in both CPu and GPe. Importantly, this oscillatory pattern was not accompanied by consistent changes in the firing rate of either CPu or GPe neurons. Cross‐correlation analysis further indicated that neurons within the CPu and GPe fired synchronously after DA blockade. Furthermore, although phase lags between neuronal discharges in the GPe and CPu were uniformly distributed prior to haloperidol administration, CPu significantly lagged GPe discharges after repeated DA blockade. Our results demonstrate that acute DA blockade is sufficient to produce synchronous oscillatory activity across basal ganglia neuron populations, and that prolonged DA blockade results in phase lag changes in pallidostriatal synchrony.
Dopamine lesion‐induced changes in subthalamic nucleus activity are not associated with alterations in firing rate or pattern in layer V neurons of the anterior cingulate cortex in anesthetized rats
Authors: Parr‐Brownlie Louise C. , Poloskey Stacey L. , Flanagan Kalynda K. , Eisenhofer Graeme , Bergstrom Debra A. , Walters Judith R.
Published: September 2007

Dysfunctional activity in the subthalamic nucleus (STN) is thought to underlie movement deficits of patients with Parkinson's disease. Alterations in STN firing patterns are also evident in the anesthetized rat model of Parkinson's disease, where studies show that loss of striatal dopamine and concomitant changes in the indirect pathway are associated with bursty and oscillatory firing patterns in STN output. However, the extent to which alterations in cortical activity contribute to changes in STN activity is unclear. As pyramidal neurons in the cingulate cortex project directly to the STN, cingulate output was assessed after dopamine lesion by simultaneously recording single‐unit and local field potential (LFP) activities in STN and anterior cingulate cortex in control, dopamine‐lesioned and non‐lesioned hemispheres of urethane‐anesthetized rats. Correlated oscillations were observed in cross‐correlograms of spike trains from STN and cingulate layer V neurons with broad waveforms indicative of pyramidal neurons. One−2 weeks after dopamine cell lesion, firing rate, incidence of bursty and 0.3–2.5 Hz oscillatory activity of neurons and LFP power in the STN all increased significantly. In contrast, firing rate, incidence of bursty and 0.3–2.5 Hz oscillatory activity of cingulate layer V putative pyramidal neurons and power in cingulate LFPs did not differ significantly between dopamine‐lesioned, non‐lesioned or control hemispheres, despite significant loss of dopamine in the lesioned cingulate cortex. Data show that alterations in STN activity in the dopamine‐lesioned hemisphere are not associated with alterations in neuronal activity in layer V of the anterior cingulate cortex in anesthetized rats.
Spatial and temporal analysis of fMRI data on word and sentence reading
Authors: Haller Sven , Klarhoefer Markus , Schwarzbach Jens , Radue Ernst W. , Indefrey Peter
Published: September 2007

Written language comprehension at the word and the sentence level was analysed by the combination of spatial and temporal analysis of functional magnetic resonance imaging (fMRI). Spatial analysis was performed via general linear modelling (GLM). Concerning the temporal analysis, local differences in neurovascular coupling may confound a direct comparison of blood oxygenation level‐dependent (BOLD) response estimates between regions. To avoid this problem, we parametrically varied linguistic task demands and compared only task‐induced within‐region BOLD response differences across areas. We reasoned that, in a hierarchical processing system, increasing task demands at lower processing levels induce delayed onset of higher‐level processes in corresponding areas. The flow of activation is thus reflected in the size of task‐induced delay increases. We estimated BOLD response delay and duration for each voxel and each participant by fitting a model function to the event‐related average BOLD response. The GLM showed increasing activations with increasing linguistic demands dominantly in the left inferior frontal gyrus (IFG) and the left superior temporal gyrus (STG). The combination of spatial and temporal analysis allowed a functional differentiation of IFG subregions involved in written language comprehension. Ventral IFG region (BA 47) and STG subserve earlier processing stages than two dorsal IFG regions (BA 44 and 45). This is in accordance with the assumed early lexical semantic and late syntactic processing of these regions and illustrates the complementary information provided by spatial and temporal fMRI data analysis of the same data set.
Overexpression of neurotrophin‐3 enhances the mechanical response properties of slowly adapting type 1 afferents and myelinated nociceptors
Authors: McIlwrath Sabrina L. , Lawson Jeffrey J. , Anderson Collene E. , Albers Kathryn M. , Koerber H. Richard
Published: September 2007

Constitutive overexpression of neurotrophin‐3 (NT3) in murine skin results in an increased number of sensory neurons within the dorsal root ganglia, an increase of myelinated axons in cutaneous nerves, hyperinnervation of the skin, and an increased number of Merkel cells found in flank skin. Here we used a saphenous skin/nerve preparation to determine if these anatomical changes affect the functional response characteristics of cutaneous sensory neurons. Overexpression of NT3 significantly increased the responses of slowly adapting type 1 (SA1) low‐threshold mechanoreceptors and Aδ high‐threshold mechanoreceptors to suprathreshold mechanical stimulation. It also resulted in significantly faster conduction velocities of SA1 fibers. In contrast to earlier findings in flank skin, no differences were noted in the numbers of Merkel cells in the touch domes in hindlimb skin of NT3‐overexpressing mice. In addition, the number of dermal Merkel cells, located around hair follicles on the dorsum of the foot, was reduced by 55%. The increase in mechanical sensitivity was found to correlate with significant increases in the expression of acid‐sensing ion channels (ASIC) 1 and 3. Additional experiments using intracellular recordings and staining procedures confirmed that at least some cutaneous myelinated nociceptors and SA1 mechanoreceptors stained positively for both trkC and ASIC3. These results indicate that cutaneous NT3 overexpression alters the response properties of specific cutaneous sensory neurons, and that these changes may be due to the modulation of putative mechanosensitive ion channels.
Serotonin transporter deficiency in rats improves inhibitory control but not behavioural flexibility
Authors: Homberg Judith R. , Pattij Tommy , Janssen Mieke C. W. , Ronken Eric , De Boer Sietse F. , Schoffelmeer Anton N. M. , Cuppen Edwin
Published: September 2007

Impulsivity and aggression have been suggested to inversely correlate with central serotonin (5‐HT) levels in a trait‐like manner. However, this relationship is far from straightforward. In the present study we addressed the effect of lifelong reduced or absent serotonin transporter (SERT) function, which is associated with constitutively increased extracellular 5‐HT levels, on impulsivity and aggression. We used unique SERT knockout rats in a resident–intruder test, five‐choice serial reaction time task and serial reversal learning task to assay aggression, inhibitory control and behavioural flexibility, respectively. Homozygous SERT knockout rats (SERT –/–) displayed reduced aggression and improved inhibitory control, but unchanged behavioural flexibility. The behavioural phenotype of heterozygous SERT knockout rats (SERT +/–) was not different from that of wild‐type controls in any of the behavioural paradigms. We determined monoamine (metabolite) tissue levels in the medial prefrontal cortex, orbitofrontal cortex, lateral hypothalamus, raphe nuclei and cerebrospinal fluid, and found that the 5‐HT levels, but not other monoamine tissue levels, were reduced in SERT –/–rats. In addition, the 5‐hydroxyindoleacetic acid (5‐HIAA)/5‐HT ratio in cerebrospinal fluid was increased in these rats. In conclusion, our data show that the absence of the SERT affects aggression and inhibitory control, but not behavioural flexibility, characteristics that may reflect the trait‐like consequences of constitutive changes in central 5‐HT levels.
Relational care: learning to look beyond intentionality to the ‘non‐intentional’ in a caring relationship
Authors: Greenwood Dennis
Published: September 2007

Abstract  This paper considers the implications for nursing practice of what the continental philosopher Emmanuel Levinas described as the ‘non‐intentional’. The place of the non‐intentional emerges from a critique of Buber’s conception of the ‘I‐Thou’ and the ‘I‐It’ relations, and is revealed to a person in the moments prior to the grasping of conscious understanding. A specific incident that took place between a nurse and a person diagnosed with dementia is described and then used to illustrate an exploration of the ‘I‐Thou’ relation and then the non‐intentional. The nurse practitioner’s pre‐understandings of the term dementia are shown to have hindered the emergence of an ‘I‐Thou’ relation and the possibility of a non‐intentional glimpse of the otherness of the other. It is suggested here that the plausible associations that become synonymous with a diagnosis like dementia detract from attentiveness to another ‘person’. The more tangible an understanding of another person becomes, the less likely it is that a person can really experience the other as separate to their perception of them. The implications for practitioner education and learning in relation to the non‐intentional are considered, in particular the need to reflect on the immediacy of the feelings experienced in a relationship. The non‐intentional highlights how ‘I’, as a nurse practitioner, can exclude the other by imposing an understanding on what is seen and experienced in relation to another person. The ‘I’ prioritizes intentional understanding and so obscures the importance of the spontaneous response to the tear in the eye of the other, which is the basis for Levinas’s conception of the non‐intentional. The spontaneity of the non‐intentional is what Levinas believed confirmed the separateness and autonomy of the other and consequently should be the basis for a therapeutic nursing relationship with a patient.
Beyond empathy: clinical intimacy in nursing practice
Authors: Kirk Timothy W.
Published: September 2007

Abstract Understanding, shared meaning, and mutual trust lie at the heart of the therapeutic nurse–patient relationship. This article introduces the concept of clinical intimacy by applying the interpersonal process model of intimacy to the nurse–patient relationship. The distinction between complementary and reciprocal behaviours, and between intimate interactions and intimate relationships, addresses background concerns about the appropriateness of intimacy in nursing relationships. The mutual construction of meaning in the interactive process between nurses and patients is seen to lie at the heart of clinical intimacy as a hermeneutic enterprise. Intimacy is distinguished from empathy based on intentionality and the status and location of meaning. Reasons for continued investigation into clinical intimacy as an explanatory model for nursing as a hermeneutic practice are presented.
The evidence‐based practice ideologies
Authors: Mantzoukas Stefanos
Published: September 2007

Abstract  This paper puts forward the argument that there are various, competing, and antithetical evidence‐based practice (EBP) definitions and acknowledges that the different EBP definitions are based on different epistemological perspectives. However, this is not enough to understand the way in which nurse professionals choose between the various EBP formations and consequently facilitate them in choosing the most appropriate for their needs. Therefore, the current article goes beyond and behind the various EBP epistemologies to identify how individuals choose an epistemology, which consequently will assist our understanding as to how an individual chooses a specific EBP formation. Individuals choose an epistemology on the mere belief that the specific epistemology offers the ideals or ideas of best explaining or interpreting daily reality. These ideals or ideas are termed by science, history, and politics as ideology. Similarly, individual practitioners choose or should choose between the different EBP formations based on their own personal ideology. Consequently, this article proceeds to analyse the various ideologies behind different EBP definitions as to conclude that there are two broad ideologies that inform the various EBP formations, namely the ideology of truth and the ideology of individual emancipation. These two ideologies are analysed and their connections to the various EBP formations are depicted. Eventually, the article concludes that the in‐depth, critical, and intentional analysis by individual nurses of their own ideology will allow them to choose the EBP formation that is most appropriate and fitting for them, and their specific situation. Hence, the conscious analysis of individual ideology becomes the criterion for choosing between competing EBP formations and allows for best evidence to be implemented in practice. Therefore, the best way to teach EBP courses is by facilitating students to analyse their own ideology.
Connecting philosophy and practice: implications of two philosophic approaches to pain for nurses' expert clinical decision making
Authors: Pesut Barbara , McDonald Heather
Published: September 2007

Abstract  McCaffery's definition of pain as ‘whatever the patient says it is’ was truly revolutionary for nursing because of its capacity to lend credibility to the patient's pain experience. However, this definition, still widely in use, represents a particular philosophic approach to pain that has limitations for nurses' expert clinical decision making. In this paper, we trace the evolution of explanations for pain and discuss two philosophic approaches to pain that are common today. The first approach, the externalist perceptual view of pain, considers pain as a perceptual experience, one that like any perceptual experience can be ‘misperceived’ by the person having the experience. The second approach, the non‐representational view of pain, considers pain as a holistic experience, one where physical and existential aspects necessarily coincide. These two approaches, while both emphasizing the importance of believing the patient's expression, have different implications for clinical decision making. Only the first approach permits nurses to exercise the nuanced judgement that differentiates pain from other related conditions such as anxiety, suffering or meaninglessness.
‘I await your apology’: a polyphonic narrative interpretation
Authors: Cash Penelope A.
Published: September 2007

Abstract  A patient's experience unfolds through a nurse's personal conversation with herself. Conveyed through three voices, the nurse's dialogue highlights her many internal struggles; those with her conscience on what she understands to be best practice, those important to her as a person, those of an ethical nature that profoundly affect one's search for meaning, and those in the personal–professional realm driven in part by institutional culture. These multivoiced knowledges are confronted in ways that foreground language and understanding as performative acts. At the same time, another journey is co‐constructed with the reader, one that weaves in‐between the symbolic and the real, engaging the imaginary in (inter)play. The nurse's response to the inner conversation with her ‘self/selves’ problematizes practice, illuminates the patient's perspective while highlighting the nurse's sense of her marginal position. Insight into reified and hegemonic assumptions, strategies of how control is maintained through organizational surveillance, trust and moral agency help to foreground personal expectations as the nurse begins to grapple with her own feelings of betrayal. Tackling these insights offers opportunities to rethink oppressive practices in the provision of care. It also enables an alternative appreciation of the everyday dilemmas confronting nurses and offers new meaning to practice.
Exploring the use of feminist philosophy within nursing research to enhance post‐positivist methodologies in the study of cardiovascular health
Authors: Routledge Faye S.
Published: September 2007

Abstract  Nursing has historically relied heavily on scientific knowledge. It is not surprising that the cardiovascular health literature has been highly influenced by the post‐positivist philosophy. The nursing discipline, as well as the cardiovascular nursing speciality, continues to benefit from research grounded within this philosophical tradition. At the same time, there are limitations associated with post‐positivism. Therefore, it is beneficial for researchers and clinicians to examine the potential contributions various philosophical traditions can have for their research and practice. This paper is an exploration of the compatibilities of feminist and post‐positivist philosophies in the study of cardiovascular nursing research. The ensuing discussion entails an examination of my clinical and research interests, the grounding of my research within the post‐positivist perspective and the significant contribution feminist philosophy can make to my research.
“Within the Pale.” British Intellectual Society and the Image of the Russian Jew, 1890–1907
Authors: JOHNSON SAM
Published: September 2007

Abstract  “Within the Pale”: This paper examines British responses to the East European Jew in the late nineteenth and early twentieth centuries. Unlike other analyses, which have concentrated on the impact of Jewish immigration to the UK and the so‐called aliens' debate, the author interprets the narrative constructed by British commentators who visited the Tsarist Empire (sometimes to specifically examine its “Jewish Question”) and who spent long periods there (either as independent observers, or as newspaper/journal correspondents). It discusses how Russian attitudes, images and allusions about Jews were transmitted to British discourse and the extent to which Anglo‐Russian boundaries of Judeophobia were intertwined. In its assessment it considers British perceptions of anti‐Tsarist persecution, life in the Pale, the Jewish‐peasant relationship and Anglo‐Jewish responses.
“It Is Not a Society for Human Beings but for Virgins”: The Girls' Friendly Society Membership Eligibility Dispute 1875–19361
Authors: RICHMOND VIVIENNE
Published: September 2007

Abstract  The Girls' Friendly Society is a neglected social purity organisation whose exclusive focus on female chastity differed from the rescue work and condemnation of the sexual double standard favoured by most of the social purity movement. The Society's rules restricted membership to virgins and prompted a sixty‐year dispute about Christian forgiveness, exposing philanthropic rivalry and clerical division. The virginity policy was maintained throughout the moral challenges presented by sexology, eugenics, birth control, sex education and post‐war emancipation, and competition from the Girl Guides, cinema and dance halls. Only rapidly declining membership forced the Society to abandon the policy in 1936.
“Disease Incarnate”: Biopolitical Discourse and Genocidal Dehumanisation in the Age of Modernity
Authors: SAVAGE ROWAN
Published: September 2007

Abstract  This paper traces the development of the concept of the outgroup as a biological threat, and the relationship of this concept to the practice of genocide. The biopolitical discourse which emerged in the modern period made the practice of genocide conceivable, and constructed genocide as justifiable and as necessary. Two developments in the modern period are highlighted: firstly, the conception of the boundaried and ethnically homogenous nation‐state, and secondly, new biological theories about race, and about the spread of disease. Discourse emerging from the biological sciences dehumanised outgroups both literally and metaphorically. This dehumanisation, in combination with the ideal of the homogenous nation‐state and the new technologies of population, provided a justification and a motivation for genocide, and a model of implementation. Conceptions of the nature of dehumanisation as a process are examined, with specific reference to the role of language and metaphor, and to concepts of hygiene, purity and contamination. Particular attention is paid to eugenics and Social Darwinism, to the role of physicians in genocide, and to the relationship between medical and military vocabularies. The features of this discourse, its persistence, and its commonality in otherwise widely different genocidal episodes, are exposed through an examination of four twentieth‐century genocides (Armenia, Nazi genocide, Cambodia, and the former Yugoslavia).
A Meta‐Analytic Vision of the Effect of Ownership Structure on Firm Performance
Authors: Sánchez‐Ballesta Juan P. , García‐Meca Emma
Published: September 2007

There is a considerable volume of research on the effects of ownership structure on firm performance. However, the empirical results in this field are often conflicting and inconsistent. A meta‐analysis based on 33 studies allows an integration of the results on the association between insider ownership, ownership concentration and firm performance. The findings show that governance system, measurement of performance, and control for endogeneity moderate the effect of ownership on firm performance.
Beyond the Black Box of Demography: board processes and task effectiveness within Italian firms
Authors: Zona Fabio , Zattoni Alessandro
Published: September 2007

In this paper we analyse boards of directors as workgroups, i.e. groups of people that perform one or more tasks within an organisational context. Building on previous studies, we developed a model that relates group's social‐psychological processes to three different board tasks: service, monitoring and networking. We tested our model through a survey on 301 large manufacturing firms in Italy. Our findings support the idea that (a) process variables and, to a limited extent, demographic variables significantly influence board task performance; (b) board processes have a different impact on each specific board task; (c) board task performance varies depending upon firm and industry characteristics.
Estimating the Cost of Executive Stock Options: evidence from Switzerland
Authors: Drobetz Wolfgang , Pensa Pascal , Schmid Markus M.
Published: September 2007

It is often argued that Black‐Scholes (1973) values overstate the subjective value of stock options granted to risk‐averse and under‐diversified executives. We construct a “representative” Swiss executive and extend the certainty‐equivalence approach presented by Hall and Murphy (2002) to assess the value‐cost wedge of executive stock options. Even with low coefficients of relative risk aversion, the discount can be above 50 per cent compared to the Black‐Scholes values. Regression analysis reveals that the equilibrium level of executive compensation is explained by economic determinant variables such as firm size and growth opportunities, whereas the pay‐for‐performance sensitivity remains largely unexplained. Firms with larger boards of directors pay higher wages, indicating potentially unresolved agency conflicts. We reject the hypothesis that cross‐sectional differences in the amount of executive pay vanish when risk‐adjusted values are used as the dependent variable.
Benchmarking Greek Corporate Governance against Different Standards
Authors: Florou Annita , Galarniotis Argiris
Published: September 2007

The rapidly increasing worldwide focus on corporate governance has resulted in a proliferation of rating systems that proxy for governance quality. This study develops a governance rating for Greek listed companies by benchmarking their governance structures against three levels: (a) the minimum requirements under Greek regulation (lower level); (b) the incremental recommendations of the Greek code (middle level); and (c) the additional international best practices, prescribed by the UK Combined Code (higher level). Using available data on 274 out of 340 Greek listed companies in 2003 and based on information collected primarily from annual reports, we find that the average governance rating at the lower level is 65.5 per cent; this scoring reduces significantly as we move to the middle and higher level. The average governance rating is 44 per cent. Second, governance scores increase with firm size. Although there may be good reasons explaining these patterns, we find that Greek companies do not provide explanations, i.e. do not practice the “comply or explain” recommendation. Third, our middle level aggregate governance rating is much lower than that reported by prior research that uses a different data gathering and weighting approach. This divergence has important methodological implications. Finally, we document a relatively high lack of transparency in relation to Greek governance practices. This is a sign of “bad governance”.
Corporate Governance and Environmental Reporting: an Australian study
Authors: Gibson Kathy , O'Donovan Gary
Published: September 2007

The development of best practice recommendations by the Corporate Governance Council (CGC) of the Australian Stock Exchange in 2003 clearly linked corporate regulators' concerns about good governance to the concept of corporate social and environmental responsibility. The CGC recommended that one way to demonstrate good governance was to use the annual report to disclose information to all legitimate stakeholders. This paper reports on the quantity and categories of environmental information disclosed in the corporate annual reports of 41 Australian companies across eight industry groups covering the period 1983–2003. This time period has seen the importance of good corporate governance practice in relation to environmental protection escalate, as demonstrated by the introduction of separate environmental and sustainability reports, the advent of triple bottom line reporting, changes in environmental legislation and the occurrence of major environmental incidents. The results of this study indicate that an increasing number of companies are disclosing environmental information, and the relative volume of such information in annual reports is increasing across all categories.
Negotiating the Minefields of Corporate Vote‐Buying
Authors: Lan Luh Luh , Heracleous Loizos
Published: September 2007

Corporate vote‐buying has received significant attention in the last decade, in several legal cases that illustrate the fine line between legitimate use of vote harnessing as a useful corporate strategic tool on one hand, and its negative connotations as a potential instrument of fraud that attempts to disfranchise shareholders on the other hand. After a brief outline of the legal history of corporate vote‐buying and the rationale for the courts’ vigilance on this practice, in both the United States and the United Kingdom, we outline some strategic reasons for vote‐buying that might make it a useful option in certain circumstances. Lastly we discuss key principles that a board of directors should bear in mind when engaging in corporate vote‐buying, so that it can employ the practice productively and legitimately, keeping in mind shareholders’ best interests and avoiding potentially costly and destructive legal challenges.
The Black Box of Board Process: gaining access to a difficult subject
Authors: Leblanc Richard , Schwartz Mark S.
Published: September 2007

Although “board process” has been identified as a critical element for future corporate governance research, gaining access to corporate boardrooms is extremely difficult if not virtually impossible for most researchers. This study attempts to address this important issue in the research methodology used to study boards. Rather than discussing the research results of the particular study however, we focus on those impediments that were faced in gaining access to boards of directors, and how these impediments were overcome. Obtaining such access included the utilisation of several non‐traditional routes. The study concludes with implications for future corporate governance research.