bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of ACTH receptor pathway genes in glucose‐dependent insulinotrophic peptide (GIP)‐dependent Cushing's syndrome
Authors: Antonini Sonir R. , Baldacchino Valérie , Tremblay Johanne , Hamet Pavel , Lacroix André
Published: December 2005

Objective  The molecular mechanisms responsible for glucose‐dependent insulinotrophic peptide receptor or gastric inhibitory polypeptide receptor (GIPR) ectopic expression and function in GIP‐dependent Cushing's syndrome (CS) are still unknown. GIPR presumably acts, like the ACTH receptor (ACTHR), through the Gs protein/cyclic AMP/protein kinase A (PKA) pathway to stimulate steroidogenesis. We studied the expression of several genes involved in this pathway in the adrenal tissues of patients with GIP‐dependent CS.

Design and methods  RNA was extracted from adrenal tissues from nine patients with GIP‐dependent CS [seven ACTH‐independent bilateral macronodular adrenal hyperplasia (AIMAH), two adenomas], two control whole adult adrenals, two fasciculata cell‐enriched preparations from normal adrenals, seven patients with Cushing's disease (CD) and two normal pancreas. Multiplex reverse transcriptase polymerase chain reaction (RT‐PCR) evaluated the expression of GIPR, ACTHR, SF‐1, Nur77, DAX‐1, CYP11A, 3β‐HSD, CYP21, CREB and CREM genes.

Results  GIPR mRNA was overexpressed in all GIP‐dependent cases. In normal adrenals and in the adrenal tissues from patients with CD, minimal amounts of GIPR mRNA were detected. ACTHR mRNA expression was observed in all GIP‐dependent adrenal tissues. The expression of steroidogenic enzymes and some specific and ubiquitous transcription factors (TFs) involved in the ACTHR cascade was significantly reduced.

Conclusions  Our results indicate that the expression of ACTHR and other genes located downstream in the ACTHR cascade, including steroidogenic enzymes genes and some transcription factors, are relatively suppressed in GIP‐dependent CS. Although the expression of aberrant receptors plays an important role in steroidogenesis and initiation of cell proliferation, additional genetic events might occur, altering the activity of the ACTHR pathway.
Clothing size as an indicator of adiposity, ischaemic heart disease and cardiovascular risks
Authors: Han T. S. , Gates E. , Truscott E. , Lean M. E. J.
Published: December 2005

Objective  To relate subjects’ clothing sizes to waist circumference, body mass index (BMI) and to the risks of ischaemic heart disease, hypertension and diabetes mellitus, and to derive cut‐off levels of clothing size that correspond to increased health risks.

Design  Cross‐sectional study.

Setting  Glasgow Royal Infirmary.

Participants  A stratified subsample of 201 men and 161 women aged 27–67 years from the Glasgow monitoring coronary (MONICA) risk factor survey.

Main outcome measures  Measured waist, weight and height, blood pressure and history of ischaemic heart disease (angina, myocardial infarction or angioplasty), hypertension and diabetes mellitus, and medications.

Results  There were 15.5% of men and 11.2% of women with ischaemic heart disease, 14.9% of men and 12.4% of women with hypertension, and 4.5% of men and 3.1% of women with diabetes mellitus. Age and smoking adjusted prevalences of these cardiovascular risks, as well as increased adiposity (waist circumference ≥102 cm in men, ≥88 cm in women or BMI ≥ 30 kg m−2) rose with increasing clothing size. Clothing size correlated (P < 0.001) linearly with indices of adiposity. Clothing sizes which correspond to waist circumference action level 1 (94 cm in men, 80 cm in women) and action level 2 (102 cm in men, 88 cm in women) or to standardized BMI cut‐offs (25 and 30 kg m−2) were estimated. Height has minimal influences on clothing size. Compared with men with trouser waist below 36 inches or women with UK dress size below 16, the age and smoking adjusted odds ratios for the risk of having at least one of the major health problems (ischaemic heart disease, hypertension or diabetes mellitus) were 3.9 (95% CI: 1.8–8.3) in men and 7.0 (95% CI: 2.5–19.4) in women who had trouser size ≥38 inches or UK dress size ≥18, respectively.

Conclusions  The present study showed that men and women with large clothing size are at increased risk of ischaemic heart disease, hypertension and diabetes mellitus. Men's trouser size equal or larger than 38 in the UK and USA or 97 in Europe and women's dress size equal or larger than 18 in the UK or 16 in the USA or 48 in Europe could be used to promote self‐awareness of increased health risks by the general public.
Dietary problems in patients with severe chronic obstructive pulmonary disease
Authors: Grönberg A. M. , Slinde F. , Engström C.‐P. , Hulthén L. , Larsson S.
Published: December 2005

Background and aims  Low body weight and low fat‐free mass‐index (FFMI) are common in patients with severe chronic obstructive pulmonary disease (COPD). Several factors seem to contribute. The aims of the present observational study were to investigate dietary problems in patients with severe COPD and to compare dietary problems to nutritional status, energy intake and smoking habits.

Methods  Nutritional status was assessed in 73 stable outpatients using body mass index and FFMI by single‐frequency bioelectrical impedance. Lung function, smoking habits, energy intake and dietary problems were also assessed.

Results  The most frequently reported dietary problems were ‘anorexia’, ‘dyspeptic symptoms other than diarrhoea’, ‘slimming’, ‘fear of gaining weight’, ‘dyspnoea’, ‘diarrhoea’, ’depression, anxiety, solitude’. Smoking habits and gender had impact on the kind of dietary problems reported. Reporting two dietary problems correlated to low FFMI, whereas reporting one or more dietary problems correlated to decreased energy intake.

Conclusion  Dietary problems are common in the group studied and related to smoking habits and gender. Dietary problems affect energy intake and FFMI negatively. It is important to recognize dietary problems and to offer intervention of the dietary problems as a part of the dietary intervention.
Older women and dietary advice: occurrence, comprehension and compliance
Authors: Gustafsson K. , Ekblad J. , Sidenvall B.
Published: December 2005

Background  When a person becomes ill, traditional food habits may come into conflict with the disease‐related recommended diet.

Aim  The aim was to study perceptions of receiving dietary advice, the occurrence and comprehension of such advice and compliance among older women diagnosed with Parkinson's disease, stroke or rheumatoid arthritis.

Methods  The study took an ethnographic approach. Fifty‐four community‐dwelling women, 64–88 years of age, were interviewed using an open‐ended interview technique during visits to their homes.

Findings  Two themes were found: ‘dietary advice – occurrence and comprehension’ describes whether the women had received dietary advice and, if so, how they understood the information. In the theme ‘compliance with dietary advice’, two principal reasons for complying or not complying with advice were found: First, women expressed a ‘food interest’, such that they were either ‘interested in disease‐related diet’ or held a general view of the significance of foods and complied with the advice for their own ‘health interest’. Secondly, the women were ‘uninterested in food changes’. This could be because of ‘poor appetite’, ‘food and disease ambivalence’, ‘habitual and preferred foods’.

Conclusion  Dietary advice should be based on women's food preferences and habitual foods. It is important to inform about known relations between food and disease, but also to support eating favourite foods, thereby facilitating women's well‐being.
Interactions between peptidoglycan and the ExeAB complex during assembly of the type II secretin of Aeromonas hydrophila
Authors: Howard S. Peter , Gebhart Carol , Langen Geoffrey R. , Li Gang , Strozen Timothy G.
Published: December 2005

Aeromonas hydrophila transports extracellular protein toxins via the type II secretion system, an export mechanism comprised of numerous proteins that spans both the inner and outer membranes. Two components of this secretion system, ExeA and ExeB, form a complex in the inner membrane that functions to locate and/or assemble the ExeD secretin in the outer membrane. In the studies reported here, two‐codon insertion mutagenesis of exeA revealed that an insertion at amino acid 495 in the C‐terminal region of ExeA did not alter ExeAB complex formation yet completely abrogated its involvement in ExeD secretin assembly and thus rendered the bacteria secretion negative. In silico analysis of protein motifs with similar amino acid profiles revealed that this amino acid is located within a putative peptidoglycan (PG) binding motif in the periplasmic domain of ExeA. Substitution mutations of three highly conserved amino acids in the motif were constructed. In cells expressing each of these mutants, the ability to assemble the ExeD secretin or secrete aerolysin was lost, while ExeA retained the ability to form a complex with ExeB. In in vivo cross‐linking experiments, wild‐type ExeA could be cross‐linked to PG, whereas the three substitution mutants of ExeA could not. These data indicate that PG binding and/or remodelling plays a role in the function of the ExeAB complex during assembly of the ExeD secretin.
Stem and leaf gas exchange and their responses to fire in a north Australian tropical savanna
Authors: CERNUSAK LUCAS A. , HUTLEY LINDSAY B. , BERINGER JASON , TAPPER NIGEL J.
Published: December 2005

We measured stem CO2 efflux and leaf gas exchange in a tropical savanna ecosystem in northern Australia, and assessed the impact of fire on these processes. Gas exchange of mature leaves that flushed after a fire showed only slight differences from that of mature leaves on unburned trees. Expanding leaves typically showed net losses of CO2 to the atmosphere in both burned and unburned trees, even under saturating irradiance. Fire caused stem CO2 efflux to decline in overstory trees, when measured 8 weeks post‐fire. This decline was thought to have resulted from reduced availability of C substrate for respiration, due to reduced canopy photosynthesis caused by leaf scorching, and to priority allocation of fixed C towards reconstruction of a new canopy. At the ecosystem scale, we estimated the annual above‐ground woody‐tissue CO2 efflux to be 275 g C m−2 ground area year−1 in a non‐fire year, or approximately 13% of the annual gross primary production.

We contrasted the canopy physiology of two co‐dominant overstory tree species, one of which has a smooth bark on its branches capable of photosynthetic re‐fixation (Eucalyptus miniata), and the other of which has a thick, rough bark incapable of re‐fixation (Eucalyptus tetrodonta). Eucalyptus miniata supported a larger branch sapwood cross‐sectional area in the crown per unit subtending leaf area, and had higher leaf stomatal conductance and photosynthesis than E. tetrodonta. Re‐fixation by photosynthetic bark reduces the C cost of delivering water to evaporative sites in leaves, because it reduces the net C cost of constructing and maintaining sapwood. We suggest that re‐fixation allowed leaves of E. miniata to photosynthesize at higher rates than those of E. tetrodonta, while the two invested similar amounts of C in the maintenance of branch sapwood.
Changes in electroencephalographic activities following pressure stimulation in humans
Authors: ISHITANI NORIHITO , MASUMOTO YASUHIRO , YOSHIHARA TOSHIHIRO , YAMASAKI YOUICHI
Published: December 2005

Abstract  We investigated brain activity in response to orofacial pain in 20 healthy subjects in order to characterize the relationship between pain and changes in brain function. First, the pressure pain threshold (PPT) at the styloid process of the temporal bone (Libman's point) of 20 subjects was measured by a pressure algometer. Second, electroencephalographic (EEG) changes of 20 subjects before and after 10 s of constant pressure stimulation at Libman's point were measured. These 20 subjects were divided into two groups: 10 subjects with higher PPT (high group) and 10 subjects with lower PPT (low group). EEG change in beta activity after stimulation was greater in the low group than the high group, and there was a significant negative correlation between this change and PPT, with even minor constant stimulation inducing larger EEG change in individuals highly receptive to pain. The present study demonstrated that a relative reduction in beta activity after pain stimulation was more remarkable in subjects with lower PPT than in subjects with higher PPT, and that this change was closely related to a hemispheric balance, with even minor constant stimulation inducing changes in brain waves in individuals highly sensitive to pain.
The effect of extract of ginkgo biloba addition to olanzapine on therapeutic effect and antioxidant enzyme levels in patients with schizophrenia
Authors: ATMACA MURAD , TEZCAN ERTAN , KULOGLU MURAT , USTUNDAG BILAL , KIRTAS OZLEM
Published: December 2005

Abstract  It has been suggested that the extract of gingko biloba (EGb) may enhance the efficiency of the classic antipsychotic haloperidol in patients with chronic schizophrenia, especially on positive symptoms, and reduce serum superoxide dismutase (SOD) levels. Therefore, we decided to evaluate the therapeutic effect of EGb and to examine the effect of it on the levels of antioxidant enzymes in schizophrenic patients on olanzapine treatment. We hypothesized that EGb would have the beneficial effects on schizophrenic symptoms and might cause reductions in antioxidant enzymes. The subjects were randomly assigned to the two groups: olanzapine plus EGb (group I) (n = 15) and olanzapine alone (group II) (n = 14). The patients were evaluated at baseline and at week 8 with respect to the Positive and Negative Syndrome Scale (PANSS), serum SOD, catalase (CAT), and glutathion peroxidase (GPX) levels. At baseline, no statistically significant difference regarding the mean total PANSS scores between treatment groups was found. At the evaluation of week 8, a significant difference in mean Scale for the Assessment of Postive Symptoms (SAPS) scores but not in Scale for the Assessment of Negative Symptoms scores between groups was found. Total patients had statistically significant higher serum SOD, CAT and GPX levels compared to control groups at baseline. At 8 weeks, there were significant differences in the mean decrease in SOD and CAT levels but not in GPX levels between treatment groups. The changes in SOD and CAT levels were correlated with the change in SAPS in group I, but not in the group II. The present study supported the findings of the previous study demonstrating that EGb might enhance the efficiency of antipsychotic in patients with schizophrenia, particularly on positive symptoms of the disorder.
Substance initiation sequences among Taiwanese adolescents using methamphetamine
Authors: YEN CHENG‐FANG , YANG YI‐HSIN , KO CHIH‐HUNG , YEN JU‐YU
Published: December 2005

Abstract The aim of this study was to examine substance initiation sequences in Taiwanese adolescent methamphetamine (MAMP) users. Three hundred adolescent MAMP users were questioned about their use of cigarettes, alcohol, areca quid, benzodiazepine, glue, marijuana, MAMP and heroin. The sequences of substance use before MAMP use were determined in every subject according to their age at substance initiation. The sequences of substance initiation were compared between genders and between early‐onset and late‐onset MAMP users. The results revealed that the adolescents had used cigarettes, alcohol and areca quid before MAMP, and very few (4%) adolescents had started using MAMP before using other substances. Female MAMP users were more likely to use MAMP as their first substance and were less likely to use areca quid than males. Male early‐onset MAMP users were more likely to drink alcohol and chew areca quid before MAMP use than were late‐onset users. This study found that the sequences of substance initiation were different between genders and between the early‐onset and late‐onset MAMP users. There are several findings that are different from those in Western studies on the sequence of substance initiation in the adolescent population.
Anosognosia in Alzheimer's disease: Association with patient characteristics, psychiatric symptoms and cognitive deficits
Authors: KASHIWA YUKIKO , KITABAYASHI YURINOSUKE , NARUMOTO JIN , NAKAMURA KAEKO , UEDA HIDEKI , FUKUI KENJI
Published: December 2005

Abstract  Anosognosia is one of the major problems in the treatment and care of Alzheimer's disease (AD) patients. The aim of the study was to determine the patient characteristics, psychiatric symptoms, and cognitive deficits associated with anosognosia, because these are currently poorly understood. Eighty‐four patients who met the National Institute of Neurological and Communicative Disease and Stroke‐Alzheimer's Disease and Related Disorders Association criteria for probable AD were examined for anosognosia based on the difference between questionnaire scores of the patient and their caregiver. The relationship of anosognosia with patient characteristics (age, age at onset, duration of illness, education, Mini‐Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Hyogo Activities of Daily Living Scale (HADLS)), psychiatric symptoms (Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS)), and cognitive function (Digit Span, Word Fluency Test, Trail Making Test, Stroop Test, Raven's Coloured Progressive Matrices Test) were studied. Anosognosia showed positive correlations with age, age at onset, duration of illness, CDR, HADLS, and NPI disinhibition, and negative correlations with MMSE and GDS. Regarding cognitive function, only Part III of the Stroop Test was a predictor of anosognosia. The severity of anosognosia increased with disease progression and with a later age at onset. Subjective complaints of depression requiring self‐monitoring of mood tended to decrease and, in contrast, inhibition of socially unsuitable behavior became more difficult as anosognosia worsened. Regarding cognitive function, anosognosia appeared to be associated with response inhibition impairment. Both disinhibition, as a psychiatric symptom, and response inhibition impairment are known to be correlated with disturbance of orbitofrontal function, which therefore may be associated with anosognosia.
Abnormal foot function in diabetic patients: the altered onset of Windlass mechanism
Authors: D’Ambrogi E. , Giacomozzi C. , Macellari V. , Uccioli L.
Published: December 2005

Aim  The aim of this study was to examine foot function in the presence of diabetes‐induced alterations of the anatomical and biomechanical unit formed by the Achilles tendon, plantar fascia and metatarso‐phalangeal joints. More specifically, we focused on the Windlass mechanism, the physiological mechanism which entails stiffening of the foot during propulsion.

Methods  Sixty‐one diabetic patients, with or without neuropathy, and 21 healthy volunteers were recruited. The thickness of Achilles tendon and plantar fascia was measured by ultrasound. The main biomechanical parameters of foot–floor interaction during gait were acquired by means of dedicated platforms. The range of motion of the 1st metatarso‐phalangeal joint was measured passively.

Results  The plantar fascia (PF) and Achilles tendon (AT) were significantly thickened in diabetic patients [control subjects: PF 2.0 ± 0.5 mm, AT 4.0 ± 0.5 mm; diabetic patients without neuropathy: PF 2.9 ± 1.2 mm (P = 0.002), AT 4.6 ± 1.0 mm (P = 0.016); diabetic patients with neuropathy: PF 3.0 ± 0.8 mm (P < 0.0001), AT 4.9 ± 1.7 mm (P = 0.026)]. Joint mobility was significantly reduced [control subjects: 100.0 ± 10.0°; diabetic patients without neuropathy: 54.0 ± 29.4° (P < 0.0001); diabetic patients with neuropathy: 54.9 ± 17.2° (P < 0.0001)]. Loading times and force integrals under the heel and the metatarsals increased [metatarsal loading time (% stance phase): control subjects 88.2 ± 4.1%; diabetic patients without neuropathy 90.1 ± 4.7% (P = 0.146); diabetic patients with neuropathy 91.7 ± 6.6% (P = 0.048)].

Conclusions  Increased thickness of Achilles tendon and plantar fascia, more evident in the presence of neuropathy, may contribute to an overall increase of tensile force and to the occurrence of an early Windlass mechanism, maintained throughout the whole gait cycle. This might play a significant role in the overall alteration of the biomechanics of the foot–ankle complex.
Curriculum authoring tools and inclusive classroom teaching practice: a longitudinal study
Authors: Bain Alan , Parkes Robert John
Published: December 2005

The purpose of this study was to investigate the longitudinal application of a suite of curriculum authoring tools (CATs) to inclusive classroom teaching practice in a secondary school setting. The study sought to establish whether the incorporation of the CATs into the teachers’ curriculum development and implementation covaried with improved implementation integrity of classroom teaching practice over time. A repeated measures design was used to establish whether those teachers with high levels of tool use also recorded higher levels of implementation integrity in their use of specific inclusive teaching practices. The effects of the tools were measured using 578 50‐minute classroom observations gathered over a 2.5‐year period. The results indicated that higher levels of implementation integrity in classroom practice covaried with the extent to which the tools were used for the design and implementation of curriculum.
Effects of circular motion on judgment of rotation direction and depth order in visual motion
Authors: HANADA MITSUHIKO
Published: December 2005

Abstract:  The rotation direction and depth order of a rotating sphere consisting of random dots often reverses while it is viewed under orthographic projection. However, if a short viewing distance is simulated under perspective projection, the correct rotation direction can be perceived. There are two motion cues for the rotation direction and depth order. One is the speed cue; points with higher velocities are closer to the observer. The other is the vertical motion cue; vertical motion is induced when the dots recede from or approach the observer. It was examined whether circular motion, which does not have any depth information but induces vertical velocities, masks the vertical motion cue. In Experiment 1, the effects of circular motion on the judgment of the rotation direction of a rotating sphere were examined. The magnitude of the two cues (the speed cue and the vertical velocity cue) as well as the angular speed of circular motion was varied. It was found that the performance improved as the vertical velocity increased and that the speed cue had slight effects on the judgment of the rotation direction. It was also found that the performance worsened as the angular speed of the circular motion was increased. In Experiment 2, the effects of circular motion on depth judgment of a rotating half sphere were investigated. The performance worsened as the angular speed of the circular motion increased, as in Experiment 1. These results suggest that the visual system cannot compensate perfectly for circular motion for the judgment of the rotation direction and depth order.
The role of visible persistence for perception of visual bilateral symmetry1
Authors: NIIMI RYOSUKE , WATANABE KATSUMI , YOKOSAWA KAZUHIKO
Published: December 2005

Abstract:  Although the detection of visual bilateral symmetry has been claimed to be highly efficient, the possible involvement and function of visual memory in such efficient mechanisms has rarely been examined. We hypothesized that symmetry perception is rapid, as it can be achieved from rapidly decaying information of visible persistence. To test this hypothesis, we employed a temporal integration paradigm. A symmetric dot pattern was randomly divided into two asymmetric patterns and presented successively with a blank screen presented between patterns. Observers could detect symmetry when the two patterns were presented close in time (Experiment 1), indicating that observers perceived symmetry presumably utilizing visible persistence. In addition, the inverse‐intensity effect of visible persistence (Di Lollo & Bischof, 1995) was evident in our temporal integration task of symmetry (Experiment 2). The results of the current study clearly demonstrate that the detection of symmetry can be achieved based on the visible persistence. The large capacity and high spatial precision of visible persistence might be adequate for the rapid and spatially global encoding of visual symmetry.
Facilitation of return in voluntary orienting to visual attributes1
Authors: OKUBO MATIA , MUGISHIMA YOSUKE , MISAWA GORO
Published: December 2005

Abstract:  The present study examined the effects of voluntary and automatic orienting after a relatively long interval in an attentional cueing paradigm. Facilitation of return was observed after the voluntary orienting to a designated color (Experiment 1) and motion direction (Experiment 2), whereas inhibition of return was observed after the automatic orienting to an abrupt stimulus onset (Experiment 1). These results suggest that the voluntary orienting to a visual attribute modulates subsequent processes differently from the automatic orienting to an abrupt onset. In the voluntary orienting to visual attributes, it would be advantageous to return attention to the previously attended location, which is a potential source of information.
Brain‐derived respiring mitochondria exhibit homogeneous, complete and cyclosporin‐sensitive permeability transition
Authors: Hansson Magnus J. , Månsson Roland , Mattiasson Gustav , Ohlsson Jonas , Karlsson Jenny , Keep Marcus F. , Elmér Eskil
Published: December 2005

The mitochondrial permeability transition (mPT) is increasingly implicated in neuronal cell death. In the present study, isolated respiring brain mitochondria were examined for their ability to undergo calcium‐induced mPT and their sensitivity to mPT inhibition by cyclosporin A (CsA). Previous studies have suggested a heterogeneous response to calcium, a limitation of CsA inhibition, and a relative resistance in the ability of respiring brain mitochondria to undergo mPT. Using fluorometric and electron microscopic analyses, we found that virtually the whole population of respiring brain mitochondria readily undergo mPT and swell upon calcium exposure. Further, brain mitochondria were highly sensitive to CsA which potentiated morphological recovery after transient swelling as well as completely blocked mPT induction in the presence of a low concentration of ADP. Using flow cytometry, which allows analysis of individual mitochondria, we demonstrate that both brain and liver mitochondria display homogeneous responses to calcium‐induced mPT. We conclude that the mPT is one likely target for the broad in vivo neuroprotective effects displayed by CsA when allowed to penetrate the blood–brain barrier, and that development of compounds inhibiting mPT may prove beneficial for the treatment of severe brain disease.
Identification of a novel family of G protein‐coupled receptor associated sorting proteins
Authors: Simonin Frederic , Karcher Pascale , Boeuf Julien J.‐M. , Matifas Audrey , Kieffer Brigitte L.
Published: December 2005

During the past few years several new interacting partners for G protein‐coupled receptors (GPCRs) have been discovered, suggesting that the activity of these receptors is more complex than previously anticipated. Recently, candidate G protein‐coupled receptor associated sorting protein (GASP‐1) has been identified as a novel interacting partner for the delta opioid receptor and has been proposed to determine the degradative fate of this receptor. We show here that GASP‐1 associatesin vitrowith other opioid receptors and that the interaction domain in these receptors is restricted to a small portion of the carboxyl‐terminal tail, corresponding to helix 8 in the three‐dimensional structure of rhodopsin. In addition, we show that GASP‐1 interacts with COOH‐terminus of several other GPCRs from subfamilies A and B and that two conserved residues within the putative helix 8 of these receptors are critical for the interaction with GASP‐1.In situhybridization and northern blot analysis indicate that GASP‐1 mRNA is mainly distributed throughout the central nervous system, consistent with a potential interaction with numerous GPCRsin vivo. Finally, we show that GASP‐1 is a member of a novel family comprising at least 10 members, whose genes are clustered on chromosome X. Another member of the family, GASP‐2, also interacts with the carboxyl‐terminal tail of several GPCRs. Therefore, GASP proteins may represent an important protein family regulating GPCR physiology.
Brain glycogen re‐awakened
Authors: Brown Angus M.
Published: December 2005

The mammalian brain contains glycogen, which is located predominantly in astrocytes, but its function is unclear. A principal role for brain glycogen as an energy reserve, analogous to its role in the periphery, had been universally dismissed based on its relatively low concentration, an assumption apparently reinforced by the limited duration that the brain can function in the absence of glucose. However, during insulin‐induced hypoglycaemia, where brain glucose availability is limited, glycogen content falls first in areas with the highest metabolic rate, suggesting that glycogen provides fuel to support brain function during pathological hypoglycaemia. General anaesthesia results in elevated brain glycogen suggesting quiescent neurones allow glycogen accumulation, and as long ago as the 1950s it was shown that brain glycogen accumulates during sleep, is mobilized upon waking, and that sleep deprivation results in region‐specific decreases in brain glycogen, implying a supportive functional role for brain glycogen in the conscious, awake brain. Interest in brain glycogen has recently been re‐awakened by the first continuous in vivo measurements using NMR spectroscopy, by the general acceptance of metabolic coupling between glia and neurones involving intercellular transfer of energy substrate, and by studies supporting a prominent physiological role for brain glycogen as a provider of supplemental energy substrate during periods of increased tissue energy demand, when ambient normoglycaemic glucose is unable to meet immediate energy requirements.
Methadone increases intracellular calcium in SH‐SY5Y and SH‐EP1‐hα7 cells by activating neuronal nicotinic acetylcholine receptors
Authors: Pakkanen Jukka S. , Nousiainen Heli , Yli‐Kauhaluoma Jari , Kylänlahti Irene , Möykkynen Tommi , Korpi Esa R. , Peng Jian‐Hong , Lukas Ronald J. , Ahtee Liisa , Tuominen Raimo K.
Published: December 2005

(–)‐Methadone acts as an agonist at opioid receptors. Both (+)‐ and (–)‐enantiomers of methadone have been suggested to be potent non‐competitive antagonists of α3β4 neuronal nicotinic acetylcholine receptors (nAChRs). In the present study, we have examined interactions of methadone with nAChRs by using receptor binding assays, patch‐clamp recording and calcium fluorometry imaging with SH‐SY5Y cells naturally expressing α7 and α3* nAChR subtypes and SH‐EP1‐hα7 cells heterologously expressing human α7 nAChRs. Methadone potently inhibited binding of [3H]methyllycaconitine to α7 nAChRs and that of [3H]epibatidine to α3* nAChRs. Methadone pretreatment induced up‐regulation of epibatidine binding sites in SH‐SY5Y cells. Using whole‐cell patch‐clamp recording, both isomers of methadone activated cation currents via mecamylamine‐sensitive nAChRs in SH‐SY5Y cells. Nicotine and both (+)‐ and (–)‐methadone evoked increases in [Ca2+]iin both fluo‐3AM loaded cell lines, and these effects were blocked by mecamylamine and by the α7 selective antagonist methyllycaconitine, suggesting effects of methadone as α7‐nAChR agonist. Sensitivity of sustained nicotine and methadone effects to blockade by CdCl2, ryanodine and xestospongin‐c implicates voltage‐operated Ca2+channels and intracellular Ca2+stores as downstream modulators of elevated [Ca2+]i. Collectively, our results suggest that methadone engages in complex and potentially pharmacologically significant interactions with nAChRs.
Structural biology of NCAM homophilic binding and activation of FGFR
Authors: Kiselyov Vladislav V. , Soroka Vladislav , Berezin Vladimir , Bock Elisabeth
Published: December 2005

In this review, we analyse the structural basis of the homophilic interactions of the neural cell adhesion molecule (NCAM) and the NCAM‐mediated activation of the fibroblast growth factor receptor (FGFR). Recent structural evidence suggests that NCAM molecules form cis‐dimers in the cell membrane through a high affinity interaction. These cis‐dimers, in turn, mediate low affinity trans‐interactions between cells via formation of either one‐ or two‐dimensional ‘zippers’. We provide evidence that FGFR is probably activated by NCAM very differently from the way by which it is activated by FGFs, reflecting the different conditions for NCAM–FGFR and FGF–FGFR interactions. The affinity of FGF for FGFR is approximately 106 times higher than that of NCAM for FGFR. Moreover, in the brain NCAM is constantly present on the cell surface in a concentration of about 50 µm, whereas FGFs only appear transiently in the extracellular environment and in concentrations in the nanomolar range. We discuss the structural basis for the regulation of NCAM–FGFR interactions by two molecular ‘switches’, polysialic acid (PSA) and adenosine triphosphate (ATP), which determine whether NCAM acts as a signalling or an adhesion molecule.
A 13 kDa carboxy‐terminal fragment of ApoE stabilizes Abeta hexamers
Authors: Wellnitz Sabine , Friedlein Arno , Bonanni Corinne , Anquez Vivianne , Goepfert Fabienne , Loetscher Hansruedi , Adessi Celine , Czech Christian
Published: December 2005

The pathological role of ApoE4 in Alzheimer's disease (AD) is not fully elucidated yet but there is strong evidence that ApoE is involved in Abeta deposition, which is an early hallmark of AD neuropathology. Overexpression of ApoE in neuroblastoma cells (Neuro2a) leads to the generation of an intracellular 13 kDa carboxy‐terminal fragment of ApoE comparable to fragments seen in brains of AD patients. ApoE4 generates more of this fragment than ApoE2 and E3 suggesting a potential pathological role of these fragments in Alzheimer's disease. Analysis of this intracellular ApoE4 fragment by protease digest followed by MALDI‐TOF mass spectrometry showed the proteolytic cleavage site close to residue 187 of ApoE. We have engineered and expressed the corresponding ApoE fragments in vitro. The recombinant 13 kDa carboxy‐terminal fragment inhibited fibril formation of Abeta; this contrasts with the full‐length ApoE and the corresponding amino‐terminal ApoE fragment. Moreover, we show that the 13 kDa carboxy‐terminal fragment of ApoE stabilizes the formation of Abeta hexamers. Complexes of Abeta with the 13 kDa carboxy‐terminal ApoE fragment show toxicity in PC12 cells comparable to Abeta fibrils. These data suggest that cleavage of ApoE, leading to the generation of this fragment, contributes to the pathogenic effect of ApoE4 in AD.
Integration of G protein signals by extracellular signal‐regulated protein kinases in SK‐N‐MC neuroepithelioma cells
Authors: Chan Anthony S. L. , Yeung Wendy W. S. , Wong Yung H.
Published: December 2005

Mammalian cells often receive multiple extracellular stimuli under physiological conditions, and the various signaling inputs have to be integrated for the processing of complex biological responses. G protein‐coupled receptors (GPCRs) are critical players in converting extracellular stimuli into intracellular signals. In this report, we examined the integration of different GPCR signals by mitogen‐activated protein kinases (MAPKs) using the SK‐N‐MC human brain neuroepithelioma cells as a neuronal model. Stimulation of the Gi‐coupled neuropeptide Y1and Gq‐coupled muscarinic M1acetylcholine receptors, but not the Gs‐coupled dopamine D1receptor, led to the activation of extracellular signal‐regulated kinase (ERK). All three receptors were also capable of stimulating c‐Jun NH2‐terminal kinases (JNK) and p38 MAPK. The Gi‐mediated ERK activation was completely suppressed upon inhibition of Src tyrosine kinases by PP1, while the Gq‐induced response was suppressed by both PP1 and the Ca2+chelator, BAPTA‐AM. In contrast, activations of JNK and p38 by Gs‐, Gi‐, and Gq‐coupled receptors were sensitive to PP1 and BAPTA‐AM pretreatments. Simultaneous stimulation of Gi‐ and Gq‐coupled receptors resulted in the synergistic activation of ERK, but not JNK or p38 MAPK. The Gi/Gq‐induced synergistic ERK activation was PTX‐sensitive, and appeared to be a co‐operative effect between Ca2+and Src family tyrosine kinases. Enhanced ERK activation was associated with an increase in CREB phosphorylation, while the JNK and p38‐responsive transcription factor ATF‐2 was weakly enhanced upon Gi/Gq‐induction. This report provides evidence that G protein signals can be integrated at the level of MAPK, resulting in differential effects on ERK, JNK and p38 MAPK in SK‐N‐MC cells.
Polarized distribution of nucleoside transporters in rat brain endothelial and choroid plexus epithelial cells
Authors: Redzic Zoran B. , Biringer Jean , Barnes Kay , Baldwin Stephen A. , Al‐Sarraf Hameed , Nicola Pieris A. , Young James D. , Cass Carol E. , Barrand Margery A. , Hladky Stephen B.
Published: December 2005

This study investigated mRNA expression and protein localization of equilibrative and concentrative nucleoside transporters (ENTs, CNTs) in primary cultures of rat brain endothelial cells (RBEC) and rat choroid plexus epithelial cells (RCPEC). Reverse transcriptase PCR analysis revealed that RBEC and RCPEC contained mRNA for rENT1, rENT2 and rCNT2 and for rENT1, rENT2, rCNT2 and rCNT3, respectively. Immunoblotting of membrane fractions of RBEC, fresh RCPEC and primary cultures of RCPEC revealed the presence of rENT1, rENT2 and rCNT2 proteins in all samples. Measurement of [14C]adenosine uptake into cells grown as monolayers on permeable plastic supports revealed a polarized distribution of Na+‐dependent adenosine uptake in that CNT activity was associated exclusively in membranes of RBEC facing the lower chamber (which corresponds to the surface facing the interstitial fluid in situ) and in membranes of RCPEC facing the upper chamber (which corresponds to the surface facing the cerebrospinal fluid in situ). In both RBEC and RCPEC, adenosine uptake from the opposite chambers was Na+‐independent and partially inhibited by nitrobenzylthioinosine, indicating the presence of the equilibrative sensitive transporter rENT1.
Identification and functional characterization of cereblon as a binding protein for large‐conductance calcium‐activated potassium channel in rat brain
Authors: Jo Sooyeon , Lee Kwang‐Hee , Song Sungmin , Jung Yong‐Keun , Park Chul‐Seung
Published: December 2005

Large‐conductance Ca2+‐activated K+ (BKCa) channels are activated by membrane depolarization and modulated by intracellular Ca2+. Here, we report the direct interaction of cereblon (CRBN) with the cytosolic carboxy‐terminus of the BKCa channel α subunit (Slo). Rat CRBN contained the N‐terminal domain of the Lon protease, a ‘regulators of G protein‐signaling’ (RGS)‐like domain, a leucine zipper (LZ) motif, and four putative protein kinase C (PKC) phosphorylation sites. RNA messages of rat cereblon (rCRBN) were widely distributed in different tissues with especially high‐levels of expression in the brain. Direct association of rCRBN with the BKCa channel was confirmed by immunoprecipitation in brain lysate, and the two proteins were co‐localized in cultured rat hippocampal neurons. Ionic currents evoked by the rSlo channel were dramatically suppressed upon coexpression of rCRBN. rCRBN decreased the formation of the tetrameric rSlo complex thus reducing the surface expression of functional channels. Therefore, we suggest that CRBN may play an important role in assembly and surface expression of functional BKCa channels by direct interaction with the cytosolic C‐terminus of its α‐subunit.
Retailer's Response to Alternate Manufacturer's Incentives Under a Single‐Period, Price‐Dependent, Stochastic‐Demand Framework*
Authors: Arcelus F. J. , Kumar Satyendra , Srinivasan G.
Published: December 2005

This article considers the joint development of the optimal pricing and ordering policies of a profit‐maximizing retailer, faced with (i) a manufacturer trade incentive in the form of a price discount for itself or a rebate directly to the end customer; (ii) a stochastic consumer demand dependent upon the magnitude of the selling price and of the trade incentive, that is contrasted with a riskless demand, which is the expected value of the stochastic demand; and (iii) a single‐period newsvendor‐type framework. Additional analysis includes the development of equal profit policies in either form of trade incentive, an assessment of the conditions under which a one‐dollar discount is more profitable than a one‐dollar rebate, and an evaluation of the impact upon the retailer‐expected profits of changes in either incentive or in the degree of demand uncertainty. A numerical example highlights the main features of the model. The analytical and numerical results clearly show that, as compared to the results for the riskless demand, dealing with uncertainty through a stochastic demand leads to (i) (lower) higher retail prices if additive (multiplicative) error, (ii) lower (higher) pass throughs if additive (multiplicative) error, (iii) higher claw backs in both error structures wherever applicable, and (iv) higher rebates to achieve equivalent profits in both error structures.
Pressureless Sintering of Zirconium Diboride
Authors: Chamberlain Adam L. , Fahrenholtz William G. , Hilmas Gregory E.
Published: December 2005

Zirconium diboride (ZrB2) ceramics were sintered to a relative density of ∼98% without applied external pressure. Densification studies were performed in the temperature range of 1900°–2150°C. Examination of bulk density as a function of temperature revealed that shrinkage started at ∼2100°C, with significant densification occurring at only 2150°C. At 2150°C, isothermal holds were used to determine the effect of time on relative density and microstructure. For a hold time of 540 min at 2150°C, ZrB2 pellets reached an average density of 6.02±0.04 g/cm3 (98% of theoretical) with an average grain size of 9.0±5.6 μm. Four‐point bend strength, elastic modulus, and Vickers' hardness were measured for sintered ZrB2 and compared with values reported for hot‐pressed materials. Vickers' hardness of sintered ZrB2 was 14.5±2.6 GPa, which was significantly lower when compared with 23 GPa for hot‐pressed ZrB2. Strength and elastic modulus of the ZrB2 were 444±30 MPa and 454 GPa, which were comparable with values reported for hot‐pressed ZrB2. The ability to densify ZrB2 ceramics without hot pressing should enable near‐net shape processing, which would significantly reduce the cost of fabricating ZrB2 components compared with conventional hot pressing and machining.
Synthesis of Ti3AlC2 from Ti/Al4C3/C Studied by In Situ Neutron Diffraction
Authors: Wu Erdong , Herold Kisi Erich
Published: December 2005

The reactive sintering of Ti/Al4C3/C mixtures at a temperature of 1417°±5°C to form the ternary carbide Ti3AlC2 was studied in situ by neutron powder diffraction. A series of intermediate phases occur during the synthesis process beginning with the formation of β‐Ti, TiCx (x≤1) and Ti3AlC. This is followed by the transition of Ti3AlC to Ti2AlC, after which the Ti2AlC and TiCx react with each other to form the product phase Ti3AlC2.
The Gambler: (re)placing the desire of money
Authors: Horton Stephen
Published: December 2005

Abstract:  The Gambler conjures a world of myth: not as a fiction of human consciousness but as unconscious image‐language. Its ambition is to write geography as material subject. In tracing the discourse written in the built environment the text ranges over the analyses of Marx and Freud and into the gestural worlds of Kafka and the blood sports of the ancient Colosseum. It discovers the myth of New Zealand horse racing, written in pictures in the local pub where virtual racing, abstracted from the living world, (dis)plays on the television screen. Here, finally, The Gambler comes to terms with loss.
Protein Translocation Across Biological Membranes
Authors: Wickner William , Schekman Randy
Published: December 2005

Subcellular compartments have unique protein compositions, yet protein synthesis only occurs in the cytosol and in mitochondria and chloroplasts. How do proteins get where they need to go? The first steps are targeting to an organelle and efficient translocation across its limiting membrane. Given that most transport systems are exquisitely substrate specific, how are diverse protein sequences recognized for translocation? Are they translocated as linear polypeptide chains or after folding? During translocation, how are diverse amino acyl side chains accommodated? What are the proteins and the lipid environment that catalyze transport and couple it to energy? How is translocation coordinated with protein synthesis and folding, and how are partially translocated transmembrane proteins released into the lipid bilayer? We review here the marked progress of the past 35 years and salient questions for future work. Subcellular compartments have unique protein compositions, yet protein synthesis only occurs in the cytosol and in mitochondria and chloroplasts. How do proteins get where they need to go? The first steps are targeting to an organelle and efficient translocation across its limiting membrane. Given that most transport systems are exquisitely substrate specific, how are diverse protein sequences recognized for translocation? Are they translocated as linear polypeptide chains or after folding? During translocation, how are diverse amino acyl side chains accommodated? What are the proteins and the lipid environment that catalyze transport and couple it to energy? How is translocation coordinated with protein synthesis and folding, and how are partially translocated transmembrane proteins released into the lipid bilayer? We review here the marked progress of the past 35 years and salient questions for future work.
Restoration of Auditory Nerve Synapses in Cats by Cochlear Implants
Authors: Ryugo D. K. , Kretzmer E. A. , Niparko J. K.
Published: December 2005

Congenital deafness results in abnormal synaptic structure in endings of the auditory nerve. If these abnormalities persist after restoration of auditory nerve activity by a cochlear implant, the processing of time-varying signals such as speech would likely be impaired. We stimulated congenitally deaf cats for 3 months with a six-channel cochlear implant. The device used human speech-processing programs, and cats responded to environmental sounds. Auditory nerve fibers exhibited a recovery of normal synaptic structure in these cats. This rescue of synapses is attributed to a return of spike activity in the auditory nerve and may help explain cochlear implant benefits in childhood deafness.
Response to Comment on "The Great Sumatra-Andaman Earthquake of 26 December 2004"
Authors: Lay Thorne , Kanamori Hiroo , Ammon Charles J. , Nettles Meredith , Ward Steven N. , Aster Richard , Beck Susan L. , Bilek Susan L. , Brudzinski Michael R. , Butler Rhett , DeShon Heather R. , Ekström Göran , Satake Kenji , Sipkin Stuart
Published: December 2005

We support the revised estimate of tsunami source length (∼800 km) obtained by Neetu
et al
. Sea-level monitoring with a high sampling rate, good azimuthal coverage, and real-time access, along with detailed bathymetry data around the stations, would improve source region estimation from tsunami arrival times.