bluuebunny/crossref_metadata_2025 huggingface dataset:
Single electron response of the scintillator‐light guide‐photomultiplier detector
Authors: NOVÁK L. , MÜLLEROVÁ I.
Published: January 2009

The time response of a scintillator‐light guide‐photomultiplier combination was measured with a time‐constant of 3 ns. Single detected electrons were recognizable at the output of the photomultiplier. The distribution of the number of photoelectrons produced by one detected electron and the pulse‐height distribution of the photomultiplier output pulses were analysed. Statistical noise computed from these distributions was compared with the noise produced by the dark current of the photomultiplier.
A hybrid total internal reflection fluorescence and optical tweezers microscope to study cell adhesion and membrane protein dynamics of single living cells
Authors: SNIJDER‐VAN AS M.I. , RIEGER B. , JOOSTEN B. , SUBRAMANIAM V. , FIGDOR C.G. , KANGER J.S.
Published: January 2009

The dynamics of cell surface membrane proteins plays an important role in cell–cell interactions. The onset of the interaction is typically not precisely controlled by current techniques, making especially difficult the visualization of early‐stage dynamics. We have developed a novel method where optical tweezers are used to trap cells and precisely control in space and time the initiation of interactions between a cell and a functionalized surface. This approach is combined with total internal reflection fluorescence microscopy to monitor dynamics of membrane bound proteins. We demonstrate an accuracy of ∼2 s in determining the onset of the interaction. Furthermore, we developed a data analysis method to determine the dynamics of cell adhesion and the organization of membrane molecules at the contact area. We demonstrate and validate this approach by studying the dynamics of the green fluorescent protein tagged membrane protein activated leukocyte cell adhesion molecule expressed in K562 cells upon interaction with its ligand CD6 immobilized on a coated substrate. The measured cell spreading is in excellent agreement with existing theoretical models. Active redistribution of activated leukocyte cell adhesion molecule is observed from a clustered to a more homogenous distribution upon contact initiation. This redistribution follows exponential decay behaviour with a characteristic time of 35 s.
Quantitative off‐axis electron holography of GaAs p‐n junctions prepared by focused ion beam milling
Authors: COOPER D. , TRUCHE R. , TWITCHETT‐HARRISON A.C. , DUNIN‐BORKOWSKI R.E. , MIDGLEY P.A.
Published: January 2009

Focused Ion beam (FIB) prepared GaAs p‐n junctions have been examined using off‐axis electron holography. Initial analysis of the holograms reveals an experimentally determined built‐in potential in the junctions that is significantly smaller than predicted from theory. In this paper we show that through combinations of in situ annealing and in situ biasing of the specimens, by varying the intensity of the incident electron beam, and by modifying the FIB operating parameters, we can develop an improved understanding of phenomena such as the electrically ‘inactive’ thickness and subsequently recover the predicted value of the built‐in potential of the junctions.

PACS numbers: 85.30.De
Automated identification of neurons in 3D confocal datasets from zebrafish brainstem
Authors: KAMALI M. , DAY L.J. , BROOKS D.H. , ZHOU X. , O'MALLEY D.M.
Published: January 2009

Many kinds of neuroscience data are being acquired regarding the dynamic behaviour and phenotypic diversity of nerve cells. But as the size, complexity and numbers of 3D neuroanatomical datasets grow ever larger, the need for automated detection and analysis of individual neurons takes on greater importance. We describe here a method that detects and identifies neurons within confocal image stacks acquired from the zebrafish brainstem. The first step is to create a template that incorporates the location of all known neurons within a population – in this case the population of reticulospinal cells. Once created, the template is used in conjunction with a sequence of algorithms to determine the 3D location and identity of all fluorescent neurons in each confocal dataset. After an image registration step, neurons are segmented within the confocal image stack and subsequently localized to specific locations within the brainstem template – in many instances identifying neurons as specific, individual reticulospinal cells. This image‐processing sequence is fully automated except for the initial selection of three registration points on a maximum projection image. In analysing confocal image stacks that ranged considerably in image quality, we found that this method correctly identified on average ∼80% of the neurons (if we assume that manual detection by experts constitutes ‘ground truth’). Because this identification can be generated approximately 100 times faster than manual identification, it offers a considerable time savings for the investigation of zebrafish reticulospinal neurons. In addition to its cell identification function, this protocol might also be integrated with stereological techniques to enhance quantification of neurons in larger databases. Our focus has been on zebrafish brainstem systems, but the methods described should be applicable to diverse neural architectures including retina, hippocampus and cerebral cortex.
Extremely Different Behaviours in High and Low Body Weight Lines of Chicken are Associated with Differential Expression of Genes Involved in Neuronal Plasticity
Authors: Ka S. , Lindberg J. , Strömstedt L. , Fitzsimmons C. , Lindqvist N. , Lundeberg J. , Siegel P. B. , Andersson L. , Hallböök F.
Published: January 2009

Long‐term selection (> 45 generations) for low or high body weight from the same founder population has generated two extremely divergent lines of chickens, the low (LWS) and high weight (HWS) lines, which at the age of selection (56 days) differs by more than nine‐fold in body weight. The HWS line chickens are compulsive feeders, whereas, in the LWS line, some individuals are anorexic and others have very low appetites. The involvement of the central nervous system in these behavioural differences has been experimentally supported. We compared a brain region at 0 and 56 days of age containing the major metabolic regulatory regions, including the hypothalamus and brainstem, using a global cDNA array expression analysis. The results obtained show that the long‐term selection has produced minor but multiple expression differences. Genes that regulate neuronal plasticity, such as actin filament polymerisation and brain‐derived neurotrophic factor, were identified as being differentially expressed. Genes involved in lipid metabolism were over‐represented among differentially expressed genes. The expression data confirm that neural systems regulating feeding behaviours in these lines are different. The results suggest that the lines are set in separate developmental trajectories equipped with slightly different nervous systems. We suggest that the lines adapt behaviourally different to changing situations post hatch, such as the transition from dependence on yolk to feeding, in order to obtain energy. The present study has identified and exemplifies the kind of changes that may underlie the extreme differences in such behaviours.
Elevated Aromatase Activity in Forebrain Synaptic Terminals During Song
Authors: Remage‐Healey L. , Oyama R. K. , Schlinger B. A.
Published: January 2009

The enzyme aromatase, which converts androgens into oestrogens, is expressed throughout the brain in zebra finches. Aromatase is enzymatically active in both cell bodies and synaptic terminals of neurones of the songbird brain, particularly within the forebrain motor and auditory networks. Aromatisation within synaptic terminals could thus provide localised and acute modulatory oestrogens within the forebrain during singing and/or audition. In male zebra finches, we tested the hypothesis that forebrain aromatase activity is elevated during singing behaviour and/or hearing male song. The present study reports that aromatase activity is elevated in males that were singing for 30 min compared to nonsinging males, and that this elevation occurs only within the cellular compartment that contains synaptic terminals. In a separate experiment, males that heard acoustic playback of song for 30 min exhibited no differences in aromatase activity or in aromatase mRNA levels, as revealed by quantitative polymerase chain reaction analysis. Therefore, these results indicate that activation of the motor pathway for song production is linked to local elevations in synaptic aromatase activity within the forebrain of male zebra finches. Future experiments could assess whether elevated synaptic aromatase activity during song is dependent on acute regulation of the aromatase protein.
Interferon‐α Signalling in Bovine Adrenal Chromaffin Cells: Involvement of Signal‐Transducer and Activator of Transcription 1 and 2, Extracellular Signal‐Regulated Protein Kinases 1/2 and Serine 31 Phosphorylation of Tyrosine Hydroxylase
Authors: Douglas S. A. , Bunn S. J.
Published: January 2009

Adrenal medullary chromaffin cells are an integral part of the neuroendocrine system, playing an important role in the physiological adaptation to stress. In response to a wide variety of stimuli, including acetylcholine released from the splanchnic nerve, hormones such as angiotensin II or paracrine signals such as prostaglandins, chromaffin cells synthesise and secrete catecholamines and a number of biologically active peptides. This adrenal medullary output mediates a complex and diverse stress response. We report that chromaffin cells also respond both acutely and chronically to interferon (IFN)‐α, thus providing a mechanism of interaction between the immune system and the stress response. Incubation of isolated bovine chromaffin cells maintained in culture, with IFN‐α resulted in a rapid, transient activation of the extracellular signal‐regulated protein kinase (ERK)1/2, which was maximal after 5 min. IFN‐α mediated activation of ERK1/2 appeared to be responsible for the increased phosphorylation of tyrosine hydroxylase, the rate‐limiting enzyme in catecholamine synthesis. This tyrosine hydroxylase phosphorylation was exclusively on serine 31, with no change in the phosphorylation of serine 19 or 40. This increase in the serine 31 phosphorylation of tyrosine hydroxylase was prevented by inhibition of protein kinase C or ERK1/2 activation. Incubation with IFN‐α also resulted in a time‐ and concentration‐dependent phosphorylation and nuclear translocation of signal transducer and activator of transcription proteins (STAT)1 and 2. This response was maximal after approximately 60 min. Prolonged treatment with IFN‐α (12–48 h) resulted in increased expression of STAT1 and, to a lesser extent, STAT2. Thus, these findings demonstrate that adrenal medullary chromaffin cells are responsive to IFN‐α and provide a possible cellular mechanism by which this immune‐derived signal can potentially influence and integrate with the stress response.
Rapid Regulation of Brain Oestrogen Synthesis: The Behavioural Roles of Oestrogens and their Fates
Authors: Cornil C. A.
Published: January 2009

Besides their well‐known genomic actions, oestrogens also exert effects through the activation of receptors associated with the plasma membrane that are too fast to be mediated by transcriptional activation (nongenomic effects). Although the existence of such rapid effects of oestrogens and their involvement in various biological processes are not in doubt, questions remain about the mechanisms responsible for the rapid modulations of oestrogen production that are required to sustain their nongenomic effects. Recent data indicate that the conversion of androgens into oestrogens in the brain by the enzyme aromatase can be rapidly modulated by conformational changes of the enzyme, thus providing a possible mechanism for rapid controls of the effects of oestrogens on male sexual behaviour. In this review, the data supporting this hypothesis are described. Subsequently, a few unanswered questions are discussed, such as the mechanism of oestrogen inactivation or the potential cellular sites of action of brain‐derived oestrogens on male sexual behaviour.
Patient health outcomes in psychiatric mental health nursing
Authors: MONTGOMERY P. , ROSE D. , CARTER L.
Published: January 2009

This integrative literature review examined evidence concerning the relationship between psychiatric mental health nursing interventions and patient‐focused outcomes. Empirical studies, published between 1997 and 2007, were identified and gathered by searching relevant databases and specific data sources. Although 156 articles were critically appraised, only 25 of them met the inclusion criteria. Findings from this review showed that the most frequently used outcome instruments assessed psychiatric symptom severity. Most of the instruments targeted two symptom categories: altered thoughts/perceptions and altered mood. Other outcome instruments were categorized in the following domains: self‐care, functioning, quality of life and satisfaction. The most important finding of this review is the lack of consistently strong evidence to support decisions concerning which outcome instrument or combination of instruments to recommend for routine use in practice. Based on this review, additional research to conceptualize, measure and examine the feasibility of outcome instruments sensitive to psychiatric mental health nursing interventions is recommended.
The meaning of mental health nurses experience of providing one‐to‐one observations: a phenomenological study
Authors: ROONEY C.
Published: January 2009

There has been much recent literature about the need for appropriate policies and approaches to ensure that patient's rights and standards of care are safeguarded. The focus from national policy is on suicide reduction and prevention, and the nursing literature has concentrated on the importance of engaging the patient and ensuring that there is the least amount of restriction possible. A research study was carried out to explore the perspective of mental health nurses working in these intensive situations, using a purposive sample of nursing staff from the local National Health Service Trust's acute units. A phenomenological approach to the study was chosen to allow an in‐depth exploration of the issues –‘seeing things up close’– using the philosophy of Husserl as a base. The key areas of enquiry were: to explore and amplify the experiences of nurses undertaking constant observations, including any effects that may have on nurses; to gain further understanding of the dynamics and processes involved; to discover information that can inform and support development needs. Individual taped interviews were carried out with six nurses working in an acute admission ward, and these were then transcribed and analysed using Giorgi's method of analysis. The results of this analysis showed that nurses are keenly aware of some of the professional and ethical tensions involved in the process of keeping patients safe while trying to promote recovery. Results have implications for policies, preparation and support of staff, and provide some further insights into the nature of this experience for nursing staff who are caring for patients who are presenting with risks to themselves.
Severity scoring in the ICU: a review
Authors: STRAND K. , FLAATTEN H.
Published: January 2009

Background: Patients in the intensive care unit (ICU) require huge resources because of the dysfunction of several of their vital organs. The heterogeneity and complexity of the ICU patient have generated interest in systems able to measure severity of illness as a method of predicting outcome, comparing quality‐of‐care and stratification for clinical trials.

Methods: By searching Medline and EMBASE for publications describing scoring systems in the ICU, the most frequently used systems, defined as resulting in more than 50 references, are included in this review. Scoring systems belong to one of four classes prognostic, single‐organ failure, trauma scores and organ dysfunction (OD). The different systems are described and discussed.

Results: Three different prognostic scoring systems, including several versions, four single OD scores and three OD scores, were included in this review.

Conclusion: Different forms of scoring systems are frequently used in the ICU. They have become a necessary tool to describe ICU populations and to explain differences in mortality. As there are several pitfalls related to the interpretation of the numbers supplied by the systems, they should not be used without knowledge on the science of severity scoring.
Leptin and perioperative neuroendocrine stress response with two different anaesthetic techniques
Authors: MARANA E. , SCAMBIA G. , COLICCI S. , MAVIGLIA R. , MAUSSIER M. L. , MARANA R. , PROIETTI R.
Published: January 2009

Background:Stress response to surgery is modulated by several factors, including magnitude of the injury, pain, type of procedure and choice of anaesthesia. Our purpose was to compare intra‐ and post‐operative hormonal changes during total intravenous anaesthesia (TIVA) using propofol and remifentanil vs. sevoflurane anaesthesia in a low stress level surgical model (laparoscopy).

Methods:We randomly allocated 18 patients undergoing laparoscopic surgery for benign ovarian cysts in two groups to receive either TIVA (groupA=9) or sevoflurane anaesthesia (groupB=9). Perioperative plasma levels of norepinephrine (NE), epinephrine (E), adrenocorticotropic hormone (ACTH), cortisol and leptin were measured. Blood samples were collected pre‐operatively (time 0), 30 min after the beginning of surgery (time 1), after extubation (time 2), and 2 h (time 3) and 4 h after surgery (time 4).

Results:The comparative analysis between the groups shows significantly higher values of NE (P<0.001 at time 1 andP<0.01 at time 3), E (P<0.001 at times 1 and 2;P<0.01 at time 3 andP<0.05 at time 4), ACTH (P<0.001 at times 1and 2;P<0.05 at time 3) and cortisol (P<0.001 at times 1and 2;P<0.01 at time 3;P<0.05 at time 4) in groupB.

The serum values of leptin were not significantly different between the two groups.

Conclusion:The choice of anaesthesia does not seem to affect the leptin serum levels but influences the release of stress response markers: ACTH, cortisol, NE and E.
Aspergillus flavus: an emerging non‐fumigatus Aspergillus species of significance
Authors: Krishnan Suganthini , Manavathu Elias K. , Chandrasekar Pranatharthi H.
Published: January 2009

Invasive aspergillosis is rare in immunocompetent people but contributes to significant morbidity and mortality in immunosuppressed patients. The majority (approximately 80%) of invasive Aspergillus infections is caused by Aspergillus fumigatus. The second most frequent (approximately 15–20%) pathogenic species is Aspergillus flavus and to a lesser extent, Aspergillus niger and Aspergillus terreus. Aspergillus flavus has emerged as a predominant pathogen in patients with fungal sinusitis and fungal keratitis in several institutions worldwide. To date, there has not been any publication exclusively reviewing the topic of A. flavus in the literature. This article reviews the microbiology, toxigenicity and epidemiology of A. flavus as well as describes the clinical characteristics, diagnosis and management of infections caused by this organism.
Development of TaqMan real‐time polymerase chain reaction for the detection and identification of Penicillium marneffei
Authors: Pornprasert Sakorn , Praparattanapan Jutarat , Khamwan Chantana , Pawichai Sudjai , Pimsarn Parichat , Samleerat Tanawan , Leechanachai Pranee , Supparatpinyo Khunchai
Published: January 2009

Penicillium marneffei is a dimorphic fungus, which is endemic in Southeast Asia and responsible for emerging opportunistic infections. Diagnosis of penicilliosis may be difficult when few yeast cells are present, while a gold standard diagnosis technique requires long‐term culture. In order to provide a more rapid and accurate diagnosis, we developed a TaqMan real‐time PCR to detect and identify P. marneffei DNA coding for 5.8S rRNA in purified yeast DNA and clinical samples. All P. marneffei DNA preparations could be detected using specific primers and TaqMan probe. The assay has a sensitivity to detect at least 10 yeast cells in seeded blood. Moreover, it can detect P. marneffei DNA in peripheral blood samples and blood‐culture bottles. Therefore, the real‐time PCR assay may represent a potential tool for early diagnosis of penicilliosis marneffei.
How do general practitioners in Thailand diagnose and treat patients presenting with anxiety and depression?
Authors: Lotrakul Manote , Saipanish Ratana
Published: January 2009

Aims:  To examine general practitioners’ (GPs’) diagnosis of a case vignette presenting both anxiety and depression symptoms, and to understand their treatment preferences for the case.

Methods:  A total of 1193 copies of a questionnaire were sent to doctors in primary care settings throughout Thailand. The questionnaire inquired about GPs’ demographic information and training background, as well as common psychiatric diagnoses and drug prescriptions to patients in their practise. A case vignette of a patient presenting both anxiety and depression symptoms was then given, and GPs were asked to describe their diagnosis and treatment preferences. For comparison, postal questionnaires of the same case vignette were also sent to 40 psychiatrists practising in general hospitals, asking their opinion about the diagnosis and treatment preferences.

Results:  A total of 434 questionnaires (36.4%) were returned. GPs reported that 37.7% of their patients suffered from anxiety disorders while 28.4% suffered from depressive disorders. For the patient in the case vignette, GPs made a diagnosis of anxiety disorders (53.5%) more often than depressive disorders (31.9%), whereas the psychiatrists at the general hospitals made a diagnosis of depressive disorders (54%) more often than anxiety disorders (9.1%). One‐third of the GPs prescribed only anxiolytics, while 15.4% prescribed only antidepressants. The most commonly prescribed antidepressant by GPs was amitriptyline, which 93% of GPs used at a dosage below 50 mg/day. Only 5.8% of them prescribed fluoxetine as antidepressant. The most frequently prescribed anxiolytic drug was diazepam (65.4%). The most common combination of drugs prescribed was amitriptyline and diazepam (38.7%).

Conclusion:  Compared to psychiatrists, GPs were more likely to diagnose anxiety than depression in patients with the same set of symptoms. They also preferred to use amitriptyline to treat depression, and prescribed the drug at a low dose. GPs in Thailand should be encouraged to prescribe fluoxetine for treatment of depression because it is safer and more convenient to use than tricyclic antidepressants.
Alcohol consumption and transition of mild cognitive impairment to dementia
Authors: Xu Gelin , Liu Xinfeng , Yin Qin , Zhu Wusheng , Zhang Renliang , Fan Xiaobing
Published: January 2009

Aim: Mild cognitive impairment (MCI) is a prodrome for dementia. Alcohol drinking patterns may affect cognitive functions and the effects may accumulate to a significant level at an advanced age. This study investigated the relationship between alcohol consumption and risks for dementia in a cohort of elderly patients with MCI.

Methods: Patients with suspected cognitive impairment were screened. One hundred and seventy‐six patients who met the MCI criteria were enrolled. Lifetime and daily alcohol consumptions were assessed at baseline using a self‐report questionnaire answered by patients and their caregivers. Patients were classified according to alcohol consumptions as abstainers, light–moderate and heavy drinkers. Global cognitive functions were assessed periodically with Mini‐Mental State Examination (MMSE). Enrolled patients were followed for 2 years.

Results: Of the 176 patients diagnosed as having MCI, 15 (8.5%) died, 13 (7.4%) were lost to follow up, and 66 (37.5%) developed dementia during follow up. Light–moderate alcohol drinkers had better MMSE performance than abstainers (P < 0.05) and heavy drinkers (P < 0.01) 2 years after MCI diagnosis. Patients who consumed a total of ≤300 kg alcohol prior to MCI diagnosis had less cognitive decline than patients who consumed no (P < 0.05) or >300 kg alcohol (P < 0.01). Heavy drinkers had a higher risk for dementia than abstainers (P < 0.05) and light–moderate drinkers (P < 0.05) 2 years after MCI diagnosis.

Conclusions: A J‐shaped relationship may exist between alcohol consumption and cognitive decline in MCI patients. Light–moderate alcohol drinking may be associated with decreased risks for dementia in elderly patients with MCI.
Long‐term efficacy and safety of aripiprazole in patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder: 26‐week prospective study
Authors: Kwon Jun Soo , Jang Joon Hwan , Kang Do‐Hyung , Yoo So Young , Kim Yong Ku , Cho Seong‐Jin ,   the APLUS study group
Published: January 2009

Aims: To date there have been no reports of long‐term efficacy of aripiprazole in Asian populations. The aim of the present study was therefore to investigate the long‐term efficacy, safety and tolerability of aripiprazole in a large number of patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder in Korea.

Methods: This study was a prospective, multicenter, single‐group, 26‐week open study of patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder. A total of 300 Korean patients participated in the study. The primary efficacy measure was the Positive and Negative Syndrome Scale (PANSS) total score, and secondary efficacy measures included the PANSS positive and negative subscales, Clinical Global Impression–Severity of Illness (CGI‐S). Tolerability and safety were assessed by monitoring the frequency and severity of treatment‐emergent adverse events, extrapyramidal symptoms (EPS), vital signs, weight, and laboratory tests.

Results: Aripiprazole produced rapid and significant improvements on all efficacy measures. As evidenced by PANSS total score, PANSS positive subscales and the CGI‐S scores, first‐episode drug‐naïve patients demonstrated significantly greater efficacy relative to patients who had previously experienced one or more episodes of relapse. Aripiprazole was associated with significant decrease of serum prolactin level. The subjects showed mild weight gain.

Conclusion: Aripiprazole is an effective antipsychotic in the long‐term treatment of both positive and negative symptoms. This study extends the findings of previous long‐term studies, and has found that there is no significant difference with regard to ethnicity in response to aripiprazole.
Lifetime substance abuse, family history of alcohol abuse/dependence and novelty seeking in eating disorders: Comparison study of eating disorder subgroups
Authors: Krug Isabel , Pinheiro Andrea Poyastro , Bulik Cynthia , Jiménez‐Murcia Susana , Granero Roser , Penelo Eva , Masuet Cristina , Agüera Zaida , Fernández‐Aranda Fernando
Published: January 2009

Aim:  To assess lifetime substance abuse, family history of alcohol abuse/dependence, and novelty seeking in three different eating disorder groups (anorexia nervosa–restrictive; anorexia nervosa–binge eating/purging; anorexia nervosa to bulimia nervosa).

Method:  A total sample of 371 eating disorder patients participated in the current study. Assessment measures included the prevalence of substance abuse and family history of alcohol abuse/dependence as well as the novelty‐seeking subscale of the Temperament and Character Inventory–Revised.

Results:  Significant differences across groups were detected for lifetime substance abuse, with anorexia nervosa–restrictive individuals exhibiting a significant lower prevalence than the anorexia nervosa to bulimia nervosa and anorexia nervosa–binge eating/ purging patients (P < 0.01). For family history of alcohol abuse/dependence the same pattern was observed (P = 0.04). Novelty seeking was associated with substance abuse (P = 0.002), with the anorexia nervosa to bulimia nervosa group exhibiting significantly higher scores on the novelty‐seeking scale than the other two groups (P < 0.001). But family history of alcohol abuse/dependence was not related to novelty seeking (P = 0.092).

Conclusion:  Lifetime substance abuse appears to be more prevalent in anorexia nervosa patients with bulimic features. Higher novelty‐seeking scores may be associated with diagnosis cross‐over.
Cellular transfer of macromolecules across the developing choroid plexus of Monodelphis domestica
Authors: Liddelow Shane A. , Dziegielewska Katarzyna M. , Ek C. Joakim , Johansson Pia A. , Potter Ann M. , Saunders Norman R.
Published: January 2009

Choroid plexus epithelial cells secrete cerebrospinal fluid (CSF) and transfer molecules from blood into CSF. Tight junctions between choroidal epithelial cells are functionally effective from early in development: the route of transfer is suggested to be transcellular. Routes of transfer for endogenous and exogenous plasma proteins and dextrans were studied in Monodelphis domestica (opossum). Pups at postnatal (P) days 1–65 and young adults were injected with biotinylated dextrans (3–70 kDa) and/or foetal protein fetuin. CSF, plasma and brain samples were collected from terminally anaesthetized animals. Choroid plexus cells containing plasma proteins were detected immunocytochemically. Numbers of plasma protein‐positive epithelial cells increased to adult levels by P28, but their percentage of plexus cells declined. Numbers of cells positive for biotinylated probes increased with age, while their percentage remained constant. Colocalization studies showed specificity for individual proteins in some epithelial cells. Biotinylated probes and endogenous proteins colocalized in about 10% of cells in younger animals, increasing towards 100% by adulthood. Injections of markers into the ventricles demonstrated that protein is transferred only from blood into CSF, whereas dextrans pass in both directions. These results indicate that protein and lipid‐insoluble markers are transferred by separate mechanisms present in choroid plexuses from the earliest stage of brain development, and transfer of proteins from plasma across choroid plexus epithelial cells contributes to the high protein concentration in CSF in the immature brain.
Role of protein kinase C and μ‐opioid receptor (MOPr) desensitization in tolerance to morphine in rat locus coeruleus neurons
Authors: Bailey C. P. , Llorente J. , Gabra B. H. , Smith F. L. , Dewey W. L. , Kelly E. , Henderson G.
Published: January 2009

In morphine tolerance a key question that remains to be answered is whether μ‐opioid receptor (MOPr) desensitization contributes to morphine tolerance, and if so by what cellular mechanisms. Here we demonstrate that MOPr desensitization can be observed in single rat brainstem locus coeruleus (LC) neurons following either prolonged (> 4 h) exposure to morphinein vitroor following treatment of animals with morphinein vivofor 3 days. Analysis of receptor function by an operational model indicated that with either treatment morphine could induce a profound degree (70–80%) of loss of receptor function. Ongoing PKC activity in the MOPr‐expressing neurons themselves, primarily by PKCα, was required to maintain morphine‐induced MOPr desensitization, because exposure to PKC inhibitors for only the last 30–50 min of exposure to morphine reduced the MOPr desensitization that was induced bothin vitroandin vivo. The presence of morphine was also required for maintenance of desensitization, as washout of morphine for > 2 h reversed MOPr desensitization. MOPr desensitization was homologous, as there was no change in α2‐adrenoceptor or ORL1 receptor function. These results demonstrate that prolonged morphine treatment induces extensive homologous desensitization of MOPrs in mature neurons, that this desensitization has a significant PKC‐dependent component and that this desensitization underlies the maintenance of morphine tolerance.
The complement‐derived anaphylatoxin C5a increases microglial GLT‐1 expression and glutamate uptake in a TNF‐α‐independent manner
Authors: Persson Mikael , Pekna Marcela , Hansson Elisabeth , Rönnbäck Lars
Published: January 2009

Microglia can express Na+‐dependent high‐affinity glutamate transporters during pathological conditions in the CNS. The transporter expression seems to be activation dependent, and we therefore sought to identify factors that could induce it, in addition to the well‐known effect of lipopolysaccharide (LPS) that is mediated by tumour necrosis factor‐α (TNF‐α). The complement‐derived anaphylatoxins C3a and C5a are of potential interest as the complement system is activated in nearly all insults to the nervous system, and both C3a and C5a have been shown to protect against excitotoxicity. We have found that C5a, but not C3a, increased the expression of the microglial glutamate transporter GLT‐1 in a dose‐dependent manner without eliciting or modulating the release of TNF‐α. However, the increase was not as prominent as the one induced by LPS, indicating that the microglia are in different activity states. The increase in microglial GLT‐1 expression led to an increased functional uptake of glutamate without affecting the release. This suggests that C5a‐stimulated microglia can be self‐ and neuroprotective by removing extracellular glutamate.
Development of glutamate receptors in auditory neurons from long‐term organotypic cultures of the embryonic chick hindbrain
Authors: Diaz Carmen , Martinez‐Galan Juan R. , Juiz Jose M.
Published: January 2009

We used long‐range organotypic cultures of auditory nuclei in the chick hindbrain to test the development of glutamate receptor activity in auditory neurons growing in a tissue environment that includes early deprivation of peripheral glutamatergic input, subsequent to removal of the otocyst. Cultures started at embryonic day (E)5, and lasted from 6 h to 15 days. Neuronal migration, clustering and axonal extension from the nucleus magnocellularis (NM) to the nucleus laminaris (NL) partially resembled events in vivo. However, the distinctive laminar organization of the NL was not observed. Glutamate receptor (GluR) activity was tested with optical recordings of intracellular Ca2+ in the NM. α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazoleproprionic acid (AMPA)/kainate receptors had Ca2+ responses with a time course similar to that in control slices. Peak amplitude, however, was significantly lower. N‐methyl‐d‐aspartate (NMDA)‐mediated Ca2+ responses were higher in 2‐day cultures (E5 + 2d) than in E7 explant controls, returning later to control values. Metabotropic GluRs did not elicit Ca2+ responses at standard agonist doses. Blocking NMDA or AMPA/kainate receptors with specific antagonists for 10 days in culture did not limit neuronal survival. Blocking metabotropic GluRs resulted in complete neuronal loss. Thus, ionotropic GluRs are not required for NM neuronal survival. However, their activity during development is affected when neurons grow in an in vitro environment that includes prevention of arrival of peripheral glutamatergic input.
NMDA and benzodiazepine receptors have synergistic and antagonistic effects on precursor cells in adult hippocampal neurogenesis
Authors: Petrus Dominique S. , Fabel Klaus , Kronenberg Golo , Winter Christine , Steiner Barbara , Kempermann Gerd
Published: January 2009

We studied how the noncompetitive NMDA receptor antagonist MK801 affected different stages of adult hippocampal neurogenesis in mice, and investigated how the activation of benzodiazepine receptors with diazepam interacted with the effects of MK801 on the precursor cells in the adult dentate gyrus. Our findings were: (i) one single MK801 application increased precursor cell proliferation and adult neurogenesis but not gliogenesis 4 weeks later; (ii) the number of label‐retaining precursor cells decreased after MK801 (with P = 0.06); (iii) the pro‐neurogenic effect included increased cell cycle entry of precursor cells as well as completed cell divisions, except in type‐2a cells; (iv) NMDA receptor blockade also increased the number of nestin–GFP‐expressing cells expressing calretinin; (v) diazepam alone had a very similar effect on overall precursor cell proliferation to that of MK801 alone; and (vi) diazepam, when co‐applied with MK801, abolished the suppression of divisions of type‐2a cells induced by MK801 alone, suppressed the MK801‐induced effect on proliferation of type‐2b cells and had no influence on the effects of MK801 on type‐3 cells, but did suppress the increased number of nestin–GFP‐positive cells expressing calretinin. From these results we hypothesize that, depending on the precursor cell stage, NMDA‐dependent neurotransmission has distinct effects that are partly antagonized and partly enhanced by GABAergic input. We propose that NMDA receptor‐dependent signalling maintains the precursor cells in the dentate gyrus while blocking initial stages of development and promoting more advanced stages.
Phylogenetic analysis of the triterpene cyclase protein family in prokaryotes and eukaryotes suggests bidirectional lateral gene transfer
Authors: Frickey Tancred , Kannenberg Elmar
Published: January 2009

Functional constraints to modifications in triterpene cyclase amino acid sequences make them good candidates for evolutionary studies on the phylogenetic relatedness of these enzymes in prokaryotes as well as in eukaryotes. In this study, we used a set of identified triterpene cyclases, a group of mainly bacterial squalene cyclases and a group of predominantly eukaryotic oxidosqualene cyclases, as seed sequences to identify 5288 putative triterpene cyclase homologues in publicly available databases. The Cluster Analysis of Sequences software was used to detect groups of sequences with increased pairwise sequence similarity. The sequences fall into two main clusters, a bacterial and a eukaryotic. The conserved, informative regions of a multiple sequence alignment of the family were used to construct a neighbour‐joining phylogenetic tree using the AsaturA and maximum likelihood phylogenetic tree using the PhyML software. Both analyses showed that most of the triterpene cyclase sequences were similarly grouped to the accepted taxonomic relationships of the organism the sequences originated from, supporting the idea of vertical transfer of cyclase genes from parent to offspring as the main evolutionary driving force in this protein family. However, a small group of sequences from three bacterial species (Stigmatella, Gemmata and Methylococcus) grouped with an otherwise purely eukaryotic cluster of oxidosqualene cyclases, while a small group of sequences from seven fungal species and a sequence from the fern Adiantum grouped consistently with a cluster of otherwise purely bacterial squalene cyclases. This suggests that lateral gene transfer may have taken place, entailing a transfer of oxidosqualene cyclases from eukaryotes to bacteria and a transfer of squalene cyclase from bacteria to an ancestor of the group of Pezizomycotina fungi.
Corporate Governance Convergence and Moral Relativism
Authors: West Andrew
Published: January 2009

Manuscript Type: Conceptual

Research Question/Issue: This paper frames the debate on corporate governance convergence in terms of the morality underlying corporate governance models. The claims and arguments of moral relativism are presented to provide theoretical structure to the moral aspects of corporate governance convergence, and ultimately the normative question of whether convergence should occur.

Research Findings/Results: The morality underlying different models of corporate governance has largely been ignored in the corporate governance convergence literature. A range of moral philosophies and principles that underlie the dominant corporate governance models are identified. This leads to a consideration of the claims and arguments of moral relativism relating to corporate governance. A research agenda around the claims of descriptive and meta‐ethical moral relativism, and which ultimately informs the associated normative argument, is then suggested.

Theoretical Implications: The application of moral relativism to the debate on corporate governance convergence presents a theoretical structure to the analysis and consideration of its moral aspects. This structure lends itself to further research, both empirical and conceptual.

Practical Implications: The claims and arguments of moral relativism provide a means of analyzing calls that are made for a culturally or nationally “appropriate” model of corporate governance. This can assist in providing direction for corporate governance reforms and is of particular relevance for developing countries that have inherited Western corporate governance models through colonialism.
Boards of Directors, CEO Ownership, and the Use of Non‐Financial Performance Measures in the CEO Bonus Plan
Authors: Schiehll Eduardo , Bellavance François
Published: January 2009

Manuscript Type: Empirical

Research Question/Issue: This study examines the associations between the board of director's choice to integrate non‐financial performance measures into the CEO bonus plan and two other governance mechanisms – board independence and CEO ownership – in a sample of publicly traded Canadian firms.

Research Findings/Results: The results provide evidence that the use of non‐financial performance measures in the CEO bonus plan varies predictably. Growth opportunities are positively associated with the firm's choice to integrate non‐financial information into the CEO bonus plan. The results are also sensitive to our proxy for board independence and CEO ownership in firms with high growth opportunities.

Theoretical Implications: Agency theory states that any costless performance measure providing incremental information about the agent's effort will improve the efficiency of the contract with the agent. In contrast with most of the literature in this area, which investigates pay‐performance sensitivity and governance structure, we examine an important component of pay‐for‐performance plans used to align and compensate executive actions that might not be reflected in traditional financial performance measures.

Practical Implications: This study documents that boards choose performance measures that best reflect the CEO's contribution to firm value, taking into account the firm's monitoring environment. This study therefore has policy implications regarding the need for enhanced disclosure of CEO compensation to improve investor understanding of the alignment between executive pay and firm performance.
The Relationship between Cultural Values and Political Ideology, and the Role of Political Knowledge
Authors: Michaud Kristy E. H. , Carlisle Juliet E. , Smith Eric R. A. N.
Published: January 2009

Cultural theory maintains that four worldviews—egalitarianism, individualism, hierarchicalism, and fatalism—can be used to describe people and societies. We examine survey measures of two of those worldviews—egalitarianism and individualism—to understand their relationship with belief systems. Contrary to what one might expect based on the cultural theory literature, we find that people with low levels of political knowledge seem not to have coherent worldviews regarding these issues. In contrast, people with high levels of political knowledge respond to egalitarianism and individualism questions as if they were opposite ends of a single, liberal‐conservative continuum, rather than two of four distinct worldviews. We conclude that cultural theory researchers should take account of the influence of political knowledge whenever they investigate worldviews.
The integration of chiropractors into healthcare teams: a case study from sport medicine
Authors: Theberge Nancy
Published: January 2009

This article examines the integration of chiropractors into multi‐disciplinary healthcare teams in the specialisation of sport medicine. Sport medicine is practised in a number of contexts in professional and amateur sport. The current analysis focuses on the highest levels of amateur sport, as exemplified by the Olympics. Data are taken from interviews with 35 health professionals, including physicians, physiotherapists, athletic therapists and chiropractors. A defining feature of sport medicine is an emphasis on performance, which is the basis for a client‐centred model of practice. These two elements have provided the main grounds for the inclusion of chiropractic in sport medicine. While the common understanding that ‘athletes wanted them’ has helped to secure a position for chiropractic within the system of sport medicine professions, this position is marked by ongoing tensions with other professions over the scope and content of practice, and the nature of the patient‐practitioner relationship. In the context of these tensions, chiropractors’ success in achieving acceptance on sport medicine teams is contingent on two factors: (a) reduced scope of practice in which they work primarily as manual therapists; and (b) the exemplary performance of individual practitioners who ‘fit’ into multi‐disciplinary sport medicine teams.
Saying no to the staff: an analysis of refusals in a home for people with severe communication difficulties
Authors: Finlay W. M. L. , Antaki Charles , Walton Chris
Published: January 2009

People with severe communication difficulties may attempt to exercise control over their lives by verbally or non‐verbally refusing an activity proposed by supporters. We detail examples in which such refusals are treated by care home staff as a temporary reluctance, warranting further attempts to persuade the individual to co‐operate. We identify the following conversational (and bodily) practices by which staff achieve their institutional ends: appreciating a resident's behaviour as something other than refusal; formulating the invitation again in a no‐blame format; minimising the task required; escalating the invitation to a request and an order; moving the person bodily; and positively glossing the proceedings. Dealing with refusals illustrates the dilemma faced by institutional personnel in health and care settings in accepting choices which might disrupt the efficient management of the service.
Bodies, mothers and identities: rethinking obesity and the BMI
Authors: Warin Megan , Turner Karen , Moore Vivienne , Davies Michael
Published: January 2009

Despite the intense level of attention directed towards obesity, there has been limited success in addressing the rising rates of this public health phenomenon. This paper argues that current approaches to obesity fail to consider concepts of embodiment, and in particular, that gendered and class‐based experiences of embodiment are ignored in health promotion practices and policies. Drawing on Bourdieu's concept ofhabitus, this ethnographic study sought to locate obesity within the biographies and everyday experiences of two groups of women from differing socio‐economic settings. Rather than identify with the clinical category of obesity, these women constructed identities that were refracted through a gendered and classedhabitus, and in particular, through their role as mothers. Food provision and practices were central to constructs of mothering, and these relational identities were at odds with the promotion of individual behavioural changes. Moreover, these women's daily lives were shaped by different class‐based aspects ofhabitus, such as employment. In demonstrating the ways in which obesity is enmeshed in participants’ taken‐for‐granted, everyday practices, we problematise the universality of health‐promotion messages and highlight the integral role that the critical theory ofhabitushas in understanding the embodiment of obesity.