bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethics in research involving prisoners
Authors: Pont Jörg
Published: December 2008

Research involving prisoners repeatedly went astray during the last century, culminating in the cruel medical experiments inside the Nazi concentration camps that gave rise to the Nuremberg Code. However, prisoners continued to become victims of scientific exploitation by the rapidly evolving biomedical research industry. The common roots of these abuses were the flawed philosophy that the needs of the society outweigh the needs of the individual and the researchers’ view that prisoners are cheap, easy to motivate and stable research subjects. Prisoners are vulnerable to exploitation and abuse by research because their freedom for consent can easily be undermined, and because of learning disabilities, illiteracy and language barriers prevailing within prisoner populations. Therefore, penal laws of some countries supported by a number of internationally agreed documents prohibit research involving prisoners completely. However, prisoners must also be regarded as vulnerable to the specific health problems in prisons, e.g. transmissible diseases, mental disorders and suicide ‐ problems that need to be addressed by research involving prisoners. Additionally, the participation of prisoner patients in research they directly can benefit from should be provided. Hence, it must be a common objective to find the right balance between protection from exploitation and access to research beneficial to prisoners.
Substance use patterns in newly admitted male and female South Australian prisoners using the WHOASSIST (Alcohol, Smoking and Substance Involvement Screening Test)
Authors: Holmwood Chris , Marriott Michelle , Humeniuk Rachel
Published: December 2008

Objective. To report on the patterns of substance use in newly admitted male and female South Australian prisoners using the WHO‐ASSIST screening tool (Alcohol, Smoking and Substance Involvement Screening Test) and observe the feasibility of using the ASSIST and associated Brief Intervention in this population. Data sources. Results of the first 518 prisoners screened using ASSIST in South Australian reception prisons. Results. In the first 10 months of the implementation of the WHO ASSIST, 518 clients were assessed in the 3 metropolitan intake prisons in Adelaide, Australia. This represents 31% of all male and 35% of all female prisoners admitted over this period. Injecting drug use was reported in the previous 3 months by 55% of men and 51% of women. The six most common substances used at high and moderate risk levels, in order of prevalence (from high to low) in males were tobacco, cannabis, amphetamines, opiates, alcohol, and sedatives. In women the order was tobacco, amphetamines, cannabis, opiates and sedatives equal, and alcohol. Fifty percent of men and 33% of women were using four or more substances. Overall rates of substance use related risk amongst men coming into prison are slightly greater than for women. Accessing prisoners for screening within the first few days is difficult with 55% already being released or at court or other external appointments.
Fit for prison: Special population health and fitness programme evaluation
Authors: Cashin Andrew , Potter Emily , Stevens Warren , Davidson Kerri , Muldoon Diane
Published: December 2008

Objective. To evaluate a health and fitness programme conducted within a New South Wales, Australia correctional facility for male inmates with a chronic illness. Design. A randomised control trial. Sample. Twenty male inmate participants with a chronic illness, two risk factors for developing a chronic illness or who were over the age of 40 years. Measurements. Pre and post programme health assessments that included resting blood pressure and heart rate, weight, body mass index, waist girth, peak flow measures, peripheral saturation of oxygen, blood glucose levels and 6 minute walk test. Intervention. A 12‐week structured exercise programme focusing on cardio respiratory endurance, strength and flexibility training. Results. Statistically significant improvements in resting heart rate and endurance were found. Conclusions. The health and fitness programme positively impacts on the health of inmates with a chronic illness. A further study with a larger sample size would be productive.
Evaluation of the electron density and temperature in a sliding discharge
Authors: Kelly H , Sosa R , Grondona D , Marquez A , Lago V , Artana G
Published: December 2008

A sliding discharge using two electrodes on a dielectric layer (upper electrodes) and a third electrode on its reverse side, facing the upper inter-electrode gap (lower electrode) was generated in air at atmospheric pressure. Application of a high dc negative voltage to one of the upper electrodes and to the lower electrode, and a high ac voltage to the other upper electrode generates a stable and homogeneous surface plasma (plasma sheet) in the upper electrode's gap. In this work, the plasma sheet optical emission of the spectral bands corresponding to the 0–0 transition of the second positive system of N2 (λ=337.1 nm) and the first negative system of N2+ (λ=391.4 nm) has been measured and analysed. It was found that the plasma sheet consisted of a set of cathode-directed streamers. The streamer generation frequency and its transit time across the inter-electrode gap have been studied. On the basis of a reliable atomic model to interpret the line emission, the total electron number at the streamer head and the electron temperature have been derived.
Analysis of Quality Control Substrates in Distinct Cellular Compartments Reveals a Unique Role for Rpn4p in Tolerating Misfolded Membrane Proteins
Authors: Metzger Meredith Boyle , Michaelis Susan
Published: December 2008

ER quality control (ERQC) prevents the exit of misfolded secretory and membrane proteins from the ER. A critical aspect of ERQC is a transcriptional response called the unfolded protein response (UPR), which up-regulates genes that enable cells to cope with misfolded, ER-retained proteins. In this study, we compare the transcriptional responses in yeast resulting from the acute expression of misfolded proteins residing in three different cellular compartments (the ER lumen, membrane, and cytosol), and find that each elicits a distinct transcriptional response. The classical UPR response, here-designated UPR-L, is induced by the ER lumenal misfolded protein, CPY*. The UPR-Cyto response is induced by the cytosolic protein, VHL-L158P, and is characterized by a rapid, transient induction of cytosolic chaperones similar to the heat-shock response. In contrast, the misfolded membrane protein with a cystolic lesion, Ste6p*, elicits a unique response designated UPR-M/C, characterized by the modest induction of >20 genes regulated by Rpn4p, an activator of proteasomal genes. Independently, we identified several genes required for yeast viability during UPR-M/C stress, but not UPR-L or UPR-Cyto stress. Among these is RPN4, highlighting the importance of the Rpn4p-dependent response in tolerating UPR-M/C stress. Further analysis suggests the requirement for Rpn4p reflects severe impairment of the proteasome by UPR-M/C stress.
Structural profiles of human miRNA families from pairwise clustering
Authors: Kaczkowski Bogumił , Torarinsson Elfar , Reiche Kristin , Havgaard Jakob Hull , Stadler Peter F. , Gorodkin Jan
Published: December 2008

MicroRNAs (miRNAs) are a group of small, ∼21 nt long, riboreg-ulators inhibiting gene expression at a post-transcriptional level. Their most distinctive structural feature is the foldback hairpin of their precursor pre-miRNAs. Even though each pre-miRNA deposited in miRBase has its secondary structure already predicted, little is known about the patterns of structural conservation among pre-miRNAs. We address this issue by clustering the human pre-miRNA sequences based on pairwise, sequence and secondary structure alignment using FOLDALIGN, followed by global multiple alignment of obtained clusters by WAR. As a result, the common secondary structure was successfully determined for four FOLDALIGN clusters: the RF00027 structural family of the Rfam database and three clusters with previously undescribed consensus structures.

Availability:  http://genome.ku.dk/resources/mirclust

Contact:  gorodkin@genome.ku.dk
Evaluating contributions of natural language parsers to protein–protein interaction extraction
Authors: Miyao Yusuke , Sagae Kenji , Sætre Rune , Matsuzaki Takuya , Tsujii Jun'ichi
Published: December 2008

Motivation: While text mining technologies for biomedical research have gained popularity as a way to take advantage of the explosive growth of information in text form in biomedical papers, selecting appropriate natural language processing (NLP) tools is still difficult for researchers who are not familiar with recent advances in NLP. This article provides a comparative evaluation of several state-of-the-art natural language parsers, focusing on the task of extracting protein–protein interaction (PPI) from biomedical papers. We measure how each parser, and its output representation, contributes to accuracy improvement when the parser is used as a component in a PPI system.

Results: All the parsers attained improvements in accuracy of PPI extraction. The levels of accuracy obtained with these different parsers vary slightly, while differences in parsing speed are larger. The best accuracy in this work was obtained when we combined Miyao and Tsujii's Enju parser and Charniak and Johnson's reranking parser, and the accuracy is better than the state-of-the-art results on the same data.

Availability: The PPI extraction system used in this work (AkanePPI) is available online at http://www-tsujii.is.s.u-tokyo.ac.jp/downloads/downloads.cgi. The evaluated parsers are also available online from each developer's site.

Contact:  yusuke@is.s.u-tokyo.ac.jp
Bioeconomic model for a three-zone Marine Protected Area: a case study of Medes Islands (northwest Mediterranean)
Authors: Merino Gorka , Maynou Francesc , Boncoeur Jean
Published: December 2008

Merino, G., Maynou, F., and Boncoeur, J. 2009. Bioeconomic model for a three-zone Marine Protected Area: a case study of Medes Islands (northwest Mediterranean). – ICES Journal of Marine Science, 66: 147–154. The bioeconomic effects of establishing a three-zone Marine Protected Area (MPA) are investigated. The division of the area into zones, fully protected, partially protected, and a fishing zone, permits a combination of extractive (fishing) and touristic activities. The consequences for species conservation, commercial fishing, and touristic activities are analysed for a set of different area-size distributions and fishing-effort levels. The model parameters are based on Medes Islands MPA in the northwestern Mediterranean. For the case study, the economic analysis includes revenues from scuba diving, glass-bottom boat trips, and commercial fisheries. Our results help to illustrate the benefits of the coexistence of extractive and non-extractive activities in a realistic, three-level MPA.
Type B Phosphatidylinositol-4-Phosphate 5-Kinases MediateArabidopsisandNicotiana tabacumPollen Tube Growth by Regulating Apical Pectin Secretion
Authors: Ischebeck Till , Stenzel Irene , Heilmann Ingo
Published: December 2008

Phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2] occurs in the apical plasma membrane of growing pollen tubes. Because enzymes responsible for PtdIns(4,5)P2 production at that location are uncharacterized, functions of PtdIns(4,5)P2 in pollen tube tip growth are unresolved. Two candidate genes encoding pollen-expressed Arabidopsis thaliana phosphatidylinositol-4-phosphate 5-kinases (PI4P 5-kinases) of Arabidopsis subfamily B were identified (PIP5K4 and PIP5K5), and their recombinant proteins were characterized as being PI4P 5-kinases. Pollen of T-DNA insertion lines deficient in both PIP5K4 and PIP5K5 exhibited reduced pollen germination and defects in pollen tube elongation. Fluorescence-tagged PIP5K4 and PIP5K5 localized to an apical plasma membrane microdomain in Arabidopsis and tobacco (Nicotiana tabacum) pollen tubes, and overexpression of either PIP5K4 or PIP5K5 triggered multiple tip branching events. Further studies using the tobacco system revealed that overexpression caused massive apical pectin deposition accompanied by plasma membrane invaginations. By contrast, callose deposition and cytoskeletal structures were unaltered in the overexpressors. Morphological effects depended on PtdIns(4,5)P2 production, as an inactive enzyme variant did not produce any effects. The data indicate that excessive PtdIns(4,5)P2 production by type B PI4P 5-kinases disturbs the balance of membrane trafficking and apical pectin deposition. Polar tip growth of pollen tubes may thus be modulated by PtdIns(4,5)P2 via regulatory effects on membrane trafficking and/or apical pectin deposition.
Characterization of TCTP, the Translationally Controlled Tumor Protein, fromArabidopsis thaliana
Authors: Berkowitz Oliver , Jost Ricarda , Pollmann Stephan , Masle Josette
Published: December 2008

The translationally controlled tumor protein (TCTP) is an important component of the TOR (target of rapamycin) signaling pathway, the major regulator of cell growth in animals and fungi. TCTP acts as the guanine nucleotide exchange factor of the Ras GTPase Rheb that controls TOR activity in Drosophila melanogaster. We therefore examined the role of Arabidopsis thaliana TCTP in planta. Plant TCTPs exhibit distinct sequence differences from nonplant homologs but share the key GTPase binding surface. Green fluorescent protein reporter lines show that Arabidopsis TCTP is expressed throughout plant tissues and developmental stages with increased expression in meristematic and expanding cells. Knockout of TCTP leads to a male gametophytic phenotype with normal pollen formation and germination but impaired pollen tube growth. Silencing of TCTP by RNA interference slows vegetative growth; leaf expansion is reduced because of smaller cell size, lateral root formation is reduced, and root hair development is impaired. Furthermore, these lines show decreased sensitivity to an exogenously applied auxin analog and have elevated levels of endogenous auxin. These results identify TCTP as an important regulator of growth in plants and imply a function of plant TCTP as a mediator of TOR activity similar to that known in nonplant systems.
Multiple Mechanism–Mediated Retention of a Defective Brassinosteroid Receptor in the Endoplasmic Reticulum ofArabidopsis
Authors: Hong Zhi , Jin Hua , Tzfira Tzvi , Li Jianming
Published: December 2008

Endoplasmic reticulum–mediated quality control (ERQC) is a well-studied process in yeast and mammals that retains and disposes misfolded/unassembled polypeptides. By contrast, how plants exert quality control over their secretory proteins is less clear. Here, we report that a mutated brassinosteroid receptor, bri1-5, that carries a Cys69Tyr mutation, is retained in the ER by an overvigilant ERQC system involving three different retention mechanisms. We demonstrate that bri1-5 interacts with two ER chaperones, calnexin and binding protein (BiP), and is degraded by a proteasome-independent endoplasmic reticulum–associated degradation (ERAD). Mutations in components of the calnexin/calreticulin cycle had little effect on the fidelity of the Arabidopsis thaliana ERQC for bri1-5 retention. By contrast, overexpression of bri1-5, treatment with an ERAD inhibitor, RNA interference–mediated BiP silencing, or simultaneous mutations of Cys-69 and its partner Cys-62 can mitigate this quality control, resulting in significant suppression of the bri1-5 phenotype. Thus, bri1-5 is an excellent model protein to investigate plant ERQC/ERAD in a model organism.
The C-Terminal Variable Region Specifies the Dynamic Properties ofArabidopsisMicrotubule-Associated Protein MAP65 Isotypes
Authors: Smertenko Andrei P. , Kaloriti Despina , Chang Hsin-Yu , Fiserova Jindriska , Opatrny Zdenek , Hussey Patrick J.
Published: December 2008

The microtubule-associated protein, MAP65, is a member of a family of divergent microtubule-associated proteins from different organisms generally involved in maintaining the integrity of the central spindle in mitosis. The dicotyledon Arabidopsis thaliana and the monocotyledon rice (Oryza sativa) genomes contain 9 and 11 MAP65 genes, respectively. In this work, we show that the majority of these proteins fall into five phylogenetic clades, with the greatest variation between clades being in the C-terminal random coil domain. At least one Arabidopsis and one rice isotype is within each clade, indicating a functional specification for the C terminus. In At MAP65-1, the C-terminal domain is a microtubule binding region (MTB2) harboring the phosphorylation sites that control its activity. The At MAP65 isotypes show differential localization to microtubule arrays and promote microtubule polymerization with variable efficiency in a MTB2-dependent manner. In vivo studies demonstrate that the dynamics of the association and dissociation of different MAP65 isotypes with microtubules can vary up to 10-fold and that this correlates with their ability to promote microtubule polymerization. Our data demonstrate that the C-terminal variable region, MTB2, determines the dynamic properties of individual isotypes and suggest that slower turnover is conditional for more efficient microtubule polymerization.
Private prayer as a suitable intervention for hospitalised patients: a critical review of the literature
Authors: Hollywell Claire , Walker Jan
Published: December 2008

Aim.  This critical review seeks to identify if there is evidence that private (personal) prayer is capable of improving wellbeing for adult patients in hospital.

Background.  The review was conducted in the belief that the spiritual needs of hospitalised patients may be enhanced by encouragement and support to engage in prayer.

Design.  Systematic review.

Method.  A systematic approach was used to gather evidence from published studies. In the absence of experimental research involving this type of population, evidence from qualitative and correlational studies was critically reviewed.

Results.  The findings indicate that private prayer, when measured by frequency, is usually associated with lower levels of depression and anxiety. Most of the studies that show positive associations between prayer and wellbeing were located in areas that have strong Christian traditions and samples reported a relatively high level of religiosity, church attendance and use of prayer. Church attenders, older people, women, those who are poor, less well educated and have chronic health problems appear to make more frequent use of prayer. Prayer appears to be a coping action that mediates between religious faith and wellbeing and can take different forms. Devotional prayers involving an intimate dialogue with a supportive God appear to be associated with improved optimism, wellbeing and function. In contrast, prayers that involve pleas for help may, in the absence of a pre‐existing faith, be associated with increased distress and possibly poorer function.

Conclusion.  Future research needs to differentiate the effects of different types of prayer.

Relevance to clinical practice.  Encouragement to engage in prayer should be offered only following assessment of the patient’s faith and likely content and form of prayer to be used. Hospitalised patients who lack faith and whose prayers involve desperate pleas for help are likely to need additional support from competent nursing and chaplaincy staff.
Leadership as part of the nurse consultant role: banging the drum for patient care
Authors: McIntosh Jean , Tolson Debbie
Published: December 2008

Aims and objectives.  This paper draws upon an evaluation of the first group of nurse consultants in Scotland. The evaluation aimed to identify the extent to which they fulfilled the remit of their posts which comprised four core functions. One of these functions was to provide professional leadership and this paper focuses on this element of the role and aims to explore it in relation to the attributes of transformational leadership.

Background.  Nurse consultants were introduced in the UK in 2000. Their purpose was to achieve better outcomes for patients and strengthen leadership. Nursing research identifies leadership as a key element of the role, with postholders adopting transformational leadership approaches. Research from the fields of sociology and psychology identifies difficulties in formulating a coherent theory of leadership, arguing for better understanding of leadership processes.

Design.  Qualitative.

Methods.  This paper draws on 31 semi‐structured interviews with four nurse consultants who were interviewed twice over six to nine months and 23 other ‘stakeholders’ who worked with them.

Results.  Varied leadership activity at ward, NHS Trust and strategic levels was identified. Postholders used approaches that resonated with the attributes of transformational leadership. Leadership processes included developing a vision for the service, acting as mediator and champion, and exerting control over complex change initiatives. Techniques of leadership included taking a ‘softly softly’ approach, pacing change initiatives and arguing assertively with those in senior positions. Interview findings also identified the level of preparation that was required to meet the remit of the posts, highlighting the importance of interpersonal skills and intellectual effort in achieving outcomes.

Conclusions.  Nurse consultants require considerable technical expertise, cognitive and interpersonal skills, and the ability to take risks. The data suggest that the leadership attributes required are transformational in nature but that they also exceed those identified in much of the literature. These posts require appropriate support if they are to be sustainable.

Relevance to clinical practice.  This paper adds to our understanding of the complexity of the nurse consultant role and highlights the challenge of providing appropriate professional development for postholders.
Factors associated with perceived sleep quality of nurses working on rotating shifts
Authors: Chan Moon Fai
Published: December 2008

Aims.  To explore nurses’ perceived sleep quality and examine factors that contribute to insufficient sleep quality.

Background.  Shift work is an important source of disturbances in the health and well‐being of nurses. However, nursing services must be available on a 24‐hour basis, making shift work a necessity. Sleep disorders tend to occur among nurses typically working on a rotating schedule. Although many studies related to nurses’ sleep quality have been carried out in the West, few have investigated factors linked to nurses’ sleep quality in Hong Kong.

Design.  A cross‐sectional study.

Method.  The study was conducted during the period November 2005–June 2006 in two local hospitals in Hong Kong. Nurses (n = 163) completed a self‐reported questionnaire. Demographic data and information on health status, strain and symptom levels and perceived sleep quality were collected.

Results.  More than 70% of the nurses reported having insufficient sleep and strain and symptom levels were higher in this group. Older age, perceived poor sleep status, gastrointestinal symptoms and higher strain and symptom levels were risk factors that contributed to insufficient sleep.

Conclusions.  Evaluation of internal stressors and modification of shift work schedules are important areas of future research; these should aim at finding the best compromise between productivity and employees’ sleep quality, health and performance.

Relevance to clinical practice.  Healthcare workers’ job task analysis, the evaluation of internal stressors and the modification of shift work schedules are important areas of future research and should result in the best compromise between productivity and employees’ sleep quality, health and performance.
Different Forms of Oestrogen Rapidly Upregulate Cell Proliferation in the Dentate Gyrus of Adult Female Rats
Authors: Barha C. K. , Lieblich S. E. , Galea L. A. M.
Published: December 2008

Oestrogens are known to exert significant structural and functional effects in the hippocampus of adult rodents. The dentate gyrus of the hippocampus retains the ability to produce neurones throughout adulthood and 17β‐oestradiol has been shown to influence hippocampal neurogenesis in adult female rats. The effects of other oestrogens, such as oestrone and 17α‐oestradiol, on neurogenesis have not been investigated. The present study aimed to investigate the effects of 17β‐oestradiol, oestradiol benzoate, oestrone, and 17α‐oestradiol on cell proliferation in ovariectomised adult female rats at two different time points. Young ovariectomised female rats were injected with one of the oestrogens at one of three doses. In Experiment 1, rats were exposed to the hormone for 4 h and, in Experiment 2, rats were exposed to the hormone for 30 min prior to 5‐bromo‐2‐deoxyuridine injection to label proliferating cells and their progeny. We found that young ovariectomised females responded with increased cell proliferation to most oestrogens, except oestradiol benzoate, after 30 min of exposure. However, administration of oestrogens for a longer time interval was ineffective at increasing cell proliferation. After 30 min, 17β‐oestradiol and oestrone increased cell proliferation at low (0.3 μg) and high (10 μg) doses, whereas 17α‐oestradiol increased cell proliferation at medium (1 μg) and high doses. The results of the present study indicate that different oestrogens rapidly increase cell proliferation in a dose‐dependent manner, possibly through a nonclassical, nongenomic mechanism. Future experiments should focus on further elucidating the specific pathways utilised by each oestrogen. These results have important therapeutic implications because it may be possible to use 17α‐oestradiol and lower doses of oestrogens in hormone replacement therapies.
Photoperiod Regulates Genes Encoding Melanocortin 3 and Serotonin Receptors and Secretogranins in the Dorsomedial Posterior Arcuate of the Siberian Hamster
Authors: Nilaweera K. N. , Archer Z. A. , Campbell G. , Mayer C.‐D. , Balik A. , Ross A. W. , Mercer J. G. , Ebling F. J. P. , Morgan P. J. , Barrett P.
Published: December 2008

The mechanism(s) involved in the regulation of the seasonal‐appropriate body weight of the Siberian hamster are currently unknown. We have identified photoperiodically regulated genes including VGF in a sub‐region of the arcuate nucleus termed the dorsomedial posterior arcuate (dmpARC). Gene expression changes in this nucleus so far account for a significant number of those reported as photoperiodically regulated and are therefore likely to contribute to seasonal physiological responses of the hamsters. The present study aimed to identify additional genes expressed in the dmpARC regulated by photoperiod that could be involved in regulating the activity of this nucleus with respect to seasonal physiology of the Siberian hamster. Using laser capture microdissection coupled with a microarray analysis and a candidate gene approach, we have identified several photoperiodically regulated genes in the dmpARC that are known to have roles in secretory and intracellular signalling pathways. These include secretogranin (sg) III and SgVI (secretory pathway), melanocortin 3 receptor (MC3‐R) and serotonin (5‐HT) receptors 2A and 7 (signalling pathway), all of which increase in expression under a short photoperiod. The spatial relationship between receptor signalling and potential secretory pathways was investigated by dual in situ hybridisation, which revealed that 5‐HT2A and 5‐HT7 receptors are expressed in neurones expressing VGF mRNA and that a sub‐population (approximately 40%) of these neurones express MC3‐R. These gene expression changes in dmpARC neurones may reflect the functional requirement of these neurones for seasonal physiological responses of the hamster.
The Ultradian and Circadian Rhythms of Free Corticosterone in the Brain are Not Affected by Gender: An In Vivo Microdialysis Study in Wistar Rats
Authors: Droste S. K. , De Groote L. , Lightman S. L. , Reul J. M. H. M. , Linthorst A. C. E.
Published: December 2008

Recently, we described that free corticosterone levels in the brain of male Wistar rats, as assessed by in vivo microdialysis, show an ultradian rhythm with a pulse frequency of 1.2 pulses/h. To establish whether gender influences brain free corticosterone rhythms, we studied free corticosterone levels in the female Wistar rat under baseline and stressful conditions using microdialysis in the hippocampus. Analysis of the data with the PULSAR algorithm revealed that hippocampal free corticosterone levels show a clear ultradian pattern in female rats with a pulse frequency of 1.16 ± 0.05 pulses/h between 09.00 h and 21.00 h. Further analysis showed that the pulse amplitude is significantly higher during the late afternoon/early night (15.00–21.00 h) than during the morning/early afternoon (09.00–15.00 h) phase (0.13 ± 0.03 versus 0.07 ± 0.01 μg/dl, respectively, P < 0.05). Pulse characteristics were extremely reproducible as demonstrated by the almost identical pulse parameters derived from two consecutive 24‐h periods [pulse frequency: 1.13 ± 0.09 and 1.19 ± 0.08 pulses/h; pulse amplitude: 0.11 ± 0.05 and 0.10 ± 0.02 μg/dl for day 1 and day 2 (09.00–21.00 h) respectively, P > 0.05]. Both exposure to a novel environment and forced swim stress increased hippocampal free corticosterone levels. However, the stress‐induced rise reached higher levels and was more prolonged after forced swimming (area under the curve: 46.84 ± 9.25 and 12.08 ± 1.69 arbitrary units for forced swimming and novelty stress respectively, P = 0.01). Importantly, the ultradian rhythm was rapidly restored after termination of the stress response. This is the first demonstration that the female rat brain is exposed to free corticosterone levels that follow a circadian as well as an ultradian pattern and show almost identical pulse characteristics as recently reported in male animals. These observations are of significance for further investigations into the dynamics of glucocorticoid action in the brain of both genders.
FXYD1, a Modulator of Na+,K+‐ATPase Activity, Facilitates Female Sexual Development by Maintaining Gonadotrophin‐Releasing Hormone Neuronal Excitability
Authors: Garcia‐Rudaz C. , Deng V. , Matagne V. , Ronnekleiv O. K. , Bosch M. , Han V. , Percy A. K. , Ojeda S. R.
Published: December 2008

The excitatory tone to gonadotrophin‐releasing hormone (GnRH) neurones is a critical component underlying the pubertal increase in GnRH secretion. However, the homeostatic mechanisms modulating the response of GnRH neurones to excitatory inputs remain poorly understood. A basic mechanism of neuronal homeostasis is the Na+,K+‐ATPase‐dependent restoration of Na+ and K+ transmembrane gradients after neuronal excitation. This activity is reduced in a mouse model of Rett syndrome (RTT), a neurodevelopmental disorder in which expression of FXYD1, a modulator of Na+,K+‐ATPase activity, is increased. We now report that the initiation, but not the completion of puberty, is advanced in girls with RTT, and that, in rodents, FXYD1 may contribute to the neuroendocrine regulation of female puberty by modulating GnRH neuronal excitability. Fxyd1 mRNA abundance reaches maximal levels in the female rat hypothalamus by the fourth postnatal week of life (i.e., around the time when the mode of GnRH secretion acquires an adult pattern of release). Although Fxyd1 mRNA expression is low in the hypothalamus, approximately 50% of GnRH neurones contain Fxyd1 transcripts. Whole‐cell patch recording of GnRH–EGFP neurones revealed that the neurones of Fxyd1‐null female mice respond to somatic current injections with a lower number of action potentials than wild‐type cells. Both the age at vaginal opening and at first oestrous were delayed in Fxyd1−/− mice, but adult reproductive capacity was normal. These results suggest that FXYD1 contributes to facilitating the advent of puberty by maintaining GnRH neuronal excitability to incoming transsynaptic stimulatory inputs.
Thyroid Hormone Action: Nongenomic Modulation of Neuronal Excitability in the Hippocampus
Authors: Caria M. A. , Dratman M. B. , Kow L. ‐M. , Mameli O. , Pavlides C.
Published: December 2008

Years of effort have failed to establish a generally‐accepted mechanism of thyroid hormone (TH) action in the mature brain. Recently, both morphological and pharmacological evidence have supported a direct neuroactive role for the hormone and its triiodinated metabolites. However, no direct physiological validation has been available. We now describe electrophysiological studies in vivo in which we observed that local thyroxine (T4) administration promptly inhibited field excitatory postsynaptic potentials recorded in the dentate gyrus (DG) with stimulation of the medial perforant pathway, a result that was found to be especially pronounced in hypothyroid rats. In separate in vitro experiments, we observed more subtle but statistically significant responses of hippocampal slices to treatment with the hormone. The results demonstrate that baseline firing rates of CA1 pyramidal cells were modestly reduced by pulse‐perfusion with T4. By contrast, administration of triiodothyronine (T3) was often noted to have modest enhancing effects on CA1 cell firing rates in hippocampal slices from euthyroid animals. Moreover, and more reliably, robust firing rate increases induced by norepinephrine were amplified when preceded by treatment with T3, whereas they were diminished by pretreatment with T4. These studies provide the first direct evidence for functional, nongenomic actions of TH leading to rapid changes in neuronal excitability in adult rat DG studied in vivo and highlight the opposing effects of T4 and T3 on norepinephrine‐induced responses of CA1 cells studied in vitro.
Oestrogen Modulates Hypothalamic Control of Energy Homeostasis Through Multiple Mechanisms
Authors: Roepke T. A.
Published: December 2008

The control of energy homeostasis in women is correlated with the anorectic effects of oestrogen, which can attenuate body weight gain and reduce food intake in rodent models. This review investigates the multiple signalling pathways and cellular targets that oestrogen utilises to control energy homeostasis in the hypothalamus. Oestrogen affects all of the hypothalamic nuclei that control energy homeostasis. Oestrogen controls the activity of hypothalamic neurones through gene regulation and neuronal excitability. Oestrogen’s primary cellular pathway is the control of gene transcription through the classical oestrogen receptors (ERs) (ERα and ERβ) with ERα having the primary role in energy homeostasis. Oestrogen also controls energy homeostasis through membrane‐mediated events via membrane‐associated ERs or a novel, putative membrane ER that is coupled to G‐proteins. Therefore, oestrogen is coupled to at least two receptors with multiple signalling and transcriptional pathways to mediate immediate and long‐term anorectic effects. Ultimately, it is the interactions of all the receptor‐mediated processes in hypothalamus and other areas of the central nervous system that will determine the anorectic effects of oestrogen and its control of energy homeostasis.
Diminished Metabolic Responses to Centrally‐Administered Apelin‐13 in Diet‐Induced Obese Rats Fed a High‐Fat Diet
Authors: Clarke K. J. , Whitaker K. W. , Reyes T. M.
Published: December 2008

The central administration of apelin, a recently identified adipokine, has been shown to affect food and water intake. The present study investigated whether body weight could affect an animal’s response to apelin. The effects of centrally‐administered apelin‐13 on food and water intake, activity and metabolic rate were investigated in adult male diet‐induced obese (DIO) rats fed either a high fat (32%) or control diet. Rats were administered i.c.v. apelin‐13, 15–30 min prior to lights out, and food and water intake, activity and metabolic rate were assessed. Intracerebroventricular administration of apelin‐13 decreased food and water intake and respiratory exchange ratio in DIO rats on the control diet, but had no effect in DIO rats on the high‐fat diet. In an effort to identify potential central mechanisms explaining the observed physiological responses, the mRNA level of the apelin receptor, APJ, was examined in the hypothalamus. A high‐fat diet induced an up‐regulation of the expression of the receptor. Apelin induced a down‐regulation of the receptor, but only in the DIO animals on the high‐fat diet. In conclusion, we have demonstrated a diminished central nervous system response to apelin that is coincident with obesity.
Medial Septal Area Vasopressin Receptor Subtypes in the Regulation of Urine and Sodium Excretion in Rats
Authors: De Arruda Camargo G. M. P. , De Arruda Camargo L. A. , Saad W. A.
Published: December 2008

The present study aimed to determine the effects of selective antagonists of V1a, V2, and V1a/V2(Conivaptan; Astellas Pharma Inc., Tokyo, Japan) arginine vasopressin (AVP) receptors on the flow of urine and sodium excretion induced by AVP, by means of microinjections into the medial septal area (MSA) of the rat brain. Male Holtzman rats had a guide cannula implanted into the dorsal surface of the MSA. Intravenous infusion of hypotonic saline was used to promote urinary flow, which was collected for 4 h. Pretreatment with the V1aantagonist decreased, and the V2antagonist and Conivaptan (a V1a/V2antagonist) increased, the urinary flow induced by AVP. Administration of AVP increased sodium excretion. Pretreatment with V2or V1aantagonists decreased, and Conivaptan abolished, the sodium excretion induced by AVP. These results indicate that the V1aand V2receptors of the MSA are important in the central regulation of urine and sodium excretion.
Local Corticosterone Infusion Enhances Nocturnal Pineal Melatonin Production In Vivo
Authors: Fernandes P. A. C. M. , Bothorel B. , Clesse D. , Monteiro A. W. A. , Calgari C. , Raison S. , Simonneaux V. , Markus R. P.
Published: December 2008

Melatonin, an important marker of the endogenous rhythmicity in mammals, also plays a role in the body defence against pathogens and injuries. In vitro experiments have shown that either pro‐ or anti‐inflammatory agents, acting directly in the organ, are able to change noradrenaline‐induced pineal indoleamine production. Whereas corticosterone potentiates melatonin production, incubation of the gland with tumour necrosis factor‐α decreases pineal hormonal production. In the present study, we show that nocturnal melatonin production measured by intra‐pineal microdialysis is enhanced in pineals perfused with corticosterone at concentrations similar to those measured in inflamed animals. In vitro experiments suggest that this enhancement may be due to an increase in the activity of the two enzymes that convert serotonin to N‐acetylserotonin (NAS) and NAS to melatonin. The present results support the hypothesis that the pineal gland is a sensor of inflammation mediators and that it plays a central role in the control of the inflammatory response.
Both allergic and nonallergic asthma are associated with increased FENO levels, but only in never‐smokers
Authors: Malinovschi A. , Janson C. , Högman M. , Rolla G. , Torén K. , Norbäck D. , Olin A.‐C.
Published: December 2008

Background:  Allergic asthma is consistently associated with increased FENO levels whereas divergence exists regarding the use of exhaled nitric oxide (NO) as marker of inflammation in nonallergic asthma and in asthmatic smokers. The aim of this study is to analyze the effect of having allergic or nonallergic asthma on exhaled nitric oxide levels, with special regard to smoking history.

Methods:  Exhaled NO measurements were performed in 695 subjects from Turin (Italy), Gothenburg and Uppsala (both Sweden). Current asthma was defined as self‐reported physician‐diagnosed asthma with at least one asthma symptom or attack recorded during the last year. Allergic status was defined by using measurements of specific immunoglobulin E (IgE). Smoking history was questionnaire‐assessed.

Results:  Allergic asthma was associated with 91 (60, 128) % [mean (95% CI)] increase of FENO while no significant association was found for nonallergic asthma [6 (–17, 35) %] in univariate analysis, when compared to nonatopic healthy subjects. In a multivariate analysis for never‐smokers, subjects with allergic asthma had 77 (27, 145) % higher FENO levels than atopic healthy subjects while subjects with nonallergic asthma had 97 (46, 166) % higher FENO levels than nonatopic healthy subjects. No significant asthma‐related FENO increases were noted for ex‐ and current smokers in multivariate analysis.

Conclusions:  Both allergic and nonallergic asthma are related to increased FENO levels, but only in never‐smoking subjects. The limited value of FENO to detect subjects with asthma among ex‐ and current smokers suggests the predominance of a noneosinophilic inflammatory phenotype of asthma among ever‐smokers.
No demonstrable association between HLA DR4 and in vitro collagen reactivity as determined by the production of leukocyte inhibition factor
Authors: Ström Håkan , Al‐Balaghi Sanad , Möller Erna
Published: December 2008

Eight HLA DR4 positive and 9 HLA DR4 negative healthy volunteers as well as 2 DR4 positive and 1 DR4 negative patients with rheumatoid arthritis (RA) were compared for leukocyte inhibition factor (LIF) production and lymphocyte proliferation in response to native and denatured collagen types II and I/III. Purified protein derivative (PPD) of tuberculin served as a positive control in the LIF assay and PPD and phytohaemagglutinin (PHA) in the lymphocyte proliferation test. No significant difference in responsiveness to collagen was detected between these two HLA groups. The reactivity to collagen was not affected by removal of OKT8+ lymphocytes. The present results are in conflict with earlier reports by Solinger et atl. (1981) and Solinger & Stobo (1982). The reason for the discrepancy has not been resolved.
Linkage disequilibrium between DPA1 and DPB1 alleles among Norwegian caucasoids and Japanese
Authors: Spurkland Anne , Vartdal Frode
Published: December 2008

Associations between allelés at the DPA1 and DPB1 loci were analyzed in 181 Norwegian caucasoids. Associations were observed between the DPA1 *0201 and the DPB1 *0101, *0901, *1001 and *1101 alleles. An association between DPA1 *0201 and the DPB1 *0901 allele was also observed among 23 healthy Japanese and 24 Japanese MS patients. In addition, it appeared that among Japanese the DPA1 *0201 allele may be associated to the DPB1 *0501. In conclusion, alleles at the DPA1 and DPB1 loci display different associations among Norwegian caucasoids and Japanese.
HLA‐DR,DQ nucleotide sequence polymorphisms in five Melanesian populations
Authors: Gao X. , Bhatia K. , Trent R. J. , Serjeantson S. W.
Published: December 2008

Abstract: HLA‐DRB1 nucleotide sequence polymorphisms have been examined in 304 Melanesians from the Papua New Guinean coast (Madang), islands (Rabaul) and highlands (Goroka), and from New Caledonia and Fiji. A total of 20 HLA‐DRB1 alleles were detected by oligonucleotide hybridizations of exon 2 HLA‐DRB1 polymerase chain reaction products, in a typing protocol designed to detect all 42 officially‐designated HLA‐DRB1 alleles. DRB1*1502 and 1101 alleles were the most common alleles in coastal and island Melanesians, while DRB1*1501, 1502 and 1408 predominated in Papua New Guinean highlanders. Undefined mixed lymphocyte reaction determinants in earlier studies of Melanesians could be accounted for in the present study as DRB1*0410, 1407 and 1408 in Papua New Guinean highlanders and as DRB1*1104 and 1602 in coastal people. Nucleotide sequence polymorphisms at HLA‐DQA1, ‐DQB1, ‐DRB3 and ‐DRB5 were also determined for estimating HLA‐DR,DQ allelic disequilibrium relationships; unusual haplotypes in Melanesians included DBR1*1502, DRB5*0101 and DRB1*0410, DQB1*0402. Previous claims of limited heterogeneity in the HLA‐DR allele repertoire in Melanesians are now seen to reflect limitations of early typing reagents rather than any dramatic restriction in HLA‐DR allelic diversity.
Increased serum HLA class I molecule levels in elderly human responders to influenza vaccination
Authors: Saririan Kris , Wali Andreas , Almeida Roque P. , Russo Carlo
Published: December 2008

Abstract: Increased cell surface expression and serum levels of HLA class I molecules have been shown to occur in normal elderly humans. Elderly subjects (65 years and older) generally also have a poorer response to influenza vaccine than younger adults. Some 30 to 40% of elderly subjects do not respond to influenza vaccination. Sera from 20 elderly subjects with a positive response to influenza vaccine (HAI antibody titer >40) and 20 subjects who did not respond (HAI antibody titer <40) were randomly selected and the levels of soluble HLA class I molecules determined before and after vaccination. The subjects who responded had higher serum HLA class I levels both before and after vaccination than did non‐responders. Two weeks after vaccination non‐responders showed similar serum HLA class I levels (1.78 mg/ml ± 0.62) as compared to pre‐vaccination levels (1.73 mg/ml ± 0.49). The responders showed significantly higher levels of soluble HLA class I molecules following vaccination (2.64 mg/ml ± 0.99) as compared to pre‐vaccination (2.08 mg/ml ± 0.85, p = 0.00001). Our results suggest that measuring soluble HLA class I molecules in the serum may be useful in assessing the adequacy of response to influenza vaccination in the elderly population.
Defining the common subtypes of HLA A9, A10, A28 and A19 by use of ARMS/PCR
Authors: Krausa Peter , Bodmer Julla G. , Browning Michael J.
Published: December 2008

Abstract: We describe sequence‐specific primer (SSP) combinations for use in a one‐step polymerase chain reaction (PCR) typing system to determine HLA‐A locus subtypes of A9 (A23, A24), A10 (A25, A26, A43), A28 (A*6801, A*6802, A*6901) and A19 (A*2901, A*2902, A*3001, A*3002, A31, A32, A33) from genomic DNA. SSP's were designed on the basis of the amplification refractory mutation system (ARMS) in which a mismatch at the 3’residue inhibits non‐specific amplification. The SSP combinations described extend our low‐resolution typing system, to provide a high‐definition typing of the HLA‐A locus.
HLA‐A *8001 is a member of a newly discovered ancient family of HLA‐A alleles*
Authors: Wagner Annette G. , Hughes Austin L. , Iandoll Mary L. , Stawart Dod , Herbert Susie , Watkins David I. , Hurley Carolyn Katovich , Rosen‐Bronson Sandra
Published: December 2008

Abstract: A member of a new HLA‐A locus family, HLA‐A *8001, has been characterized from 3 African‐American individuals expressing a unique HLA‐A serologic specificity. The HLA‐A *8001 sequence is most closely related to alleles of the HLA‐A1/3/11 family, although it also contains residues characteristic of the HLA‐A2/28, ‐A9, ‐A10, and ‐A19 families. More importantly, the HLA‐A*8001 sequence contains four unique nonsynonymous (amino acid replacing) nucleotide substitutions absent from all other primate A locus alleles. In addition, five other nucleotide substitutions, four nonsynonymous and one synonymous (silent). observed only in non‐human primate A locus alleles were found. Neighbor‐joining tree analysis of HLA‐A *8001 supports the notion that the HLA‐A *8001 allele is a member of a new HLA‐A locus family which was derived from the ancestral A3 lineage but diverged early in the evolution of the HLA‐A locus.