bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilising survey data to inform public policy: Comparison of the cost-effectiveness of treatment of ten mental disorders
Authors: Andrews Gavin , Issakidis Cathy , Sanderson Kristy , Corry Justine , Lapsley Helen
Published: June 2004

Background

Mental health survey data are now being used proactively to decide how the burden of disease might best be reduced.

Aims

To study the cost-effectiveness of current and optimal treatments for mental disorders and the proportion of burden avertable by each.

Method

Data for three affective, four anxiety and two alcohol use disorders and for schizophrenia were compared in terms of cost, burden averted and efficiency of current and optimal treatment. We then calculated the burden unavertable given current knowledge. The unit of health gain was a reduction in the years lived with disability (YLDs).

Results

Summing across all disorders, current treatment averted 13% of the burden, at an average cost of AUS$30 000 per YLD gained. Optimal treatment at current coverage could avert 20% of the burden, at an average cost of AUS$18 000 per YLD gained. Optimal treatment at optimal coverage could avert 28% of the burden, at AUS$16 000 per YLD gained. Sixty per cent of the burden of mental disorders was deemed to be unavertable.

Conclusions

The efficiency of treatment varied more than tenfold across disorders. Although coverage of some of the more efficient treatments should be extended, other factors justify continued use of less-efficient treatments for some disorders.
Melancholia and the probability and lethality of suicide attempts
Authors: Grunebaum Michael F. , Galfalvy Hanga C. , Oquendo Maria A. , Burke Ainsley K. , Mann J. John
Published: June 2004

We compared suicide attempts associated with melancholic v. non-melancholic major depression in 377 patients. Controlling for depression severity and other covariates, melancholia at baseline assessment was associated with more serious past suicide attempts and with the probability of suicide attempt during follow-up.
Psychiatric research in Nigeria: Bridging tradition and modernisation
Authors: Ayonrinde Oyedeji , Gureje Oye , Lawal Rahmaan
Published: June 2004

Nigeria is a large West African country, more than 900 000 km2 in area–nearly four times the size of the UK. Despite having a population of about 117 million people, 42% of whom live in cities, Nigeria has about half the population density of the UK. About a sixth of all Africans are Nigerian. The country has a diverse ethnic mix, with over 200 spoken languages, of which three (Yoruba, Hausa and Ibo) are spoken by about 60% of the population. The official language of government and educational instruction is English. There is a federal system of government and 36 states. Religious practice has a major role in Nigeria's culture; of the two main religions, Islam predominates in the northern part of the country and Christianity in the south. A large proportion of the population still embraces traditional religions exclusively, or interwoven with either Islam or Christianity.
Ten books
Authors: Subotsky Fiona
Published: June 2004

Books are an enduring passion, and yet considering which are the Top Ten in relation to my professional life is surprisingly difficult. Is it the most used-looking on my bedroom bookshelf, or in my study or hospital office? Or do I in fact never again look at the books of great influence after the contents have seeped in or conveyed one great idea? In the end, only a sample is possible, and choices repeatedly popular with others have been eliminated.
The use of ‘drug dogs' in psychiatry
Authors: Gordon Harvey , Haider Daniel
Published: June 2004

Comorbidity of severe mental illness and substance misuse is now common in general psychiatry (Regier et al, 1990), and perhaps almost standard in forensic psychiatry (Snowden, 2001). It is also reflected in child and adolescent psychiatry (Boys et al, 2003) and even in old age psychiatry (Jolley et al, 2004). The range of hazards associated with substance misuse in people with mental illnesses includes elevated risk of relapse of psychosis (Cantwell & Harrison, 1996), increased frequency of hospitalisation (Bartels et al, 1993), poorer compliance with treatment (Jablensky et al, 1992), higher levels of treatment-resistance (Bowers et al, 1990), impairment of the integrity of therapeutic regimes in hospital settings and in hostels in the community (Sandford, 1995), stress in the community (Drake & Wallach, 1989), higher rates of homelessness (Scheller-Gilkey et al, 1999), increased suicidality (Drake & Wallach, 1989), and increased potential for antisocial behaviour and crime of both an acquisitive and a violent nature (Stewart et al, 2000; Sinha & Easton, 1999). The misuse of substances is therefore a significant obstruction to the effective use of psychiatric treatment, and the financial cost associated with such clinical adversity must run into millions of pounds.
Do patients really want copies of their GP letters? A questionnaire survey of older adults and their carers
Authors: Dale Jenny , Tadros George , Adams Susan , Deshpande Nikhila
Published: June 2004

Aims and Method

The National Health Service Plan stated that all correspondence between clinicians would be copied to patients by April 2004. We wanted to find out whether this practice reflected the true desires of their patients. A questionnaire survey was therefore performed in older adults and their carers attending a psychiatric out-patient clinic.

Results

A total of 88 participants were recruited; 50 patients and 38 carers. The majority of patients and carers wanted a letter about their care but most preferred a separate, simple letter rather than a copy of the letter sent to their general practitioner.

Clinical Implications

Although this study supports the existing evidence that patients would like written information about their care, it indicates that certain patient groups might not want this in the form of copies of their medical correspondence. Further research into patient and carer preference is needed before the implementation of this policy.
Female psychiatrists' career development after flexible training
Authors: Mears Alex , Etchegoyen Alicia , Stormont Fiona , Kendall Tim , Katona Cornelius , Pajak Sarah
Published: June 2004

Aims and Method

The project gathered data from a cohort of 300 flexibly trained female consultants in psychiatry in order to understand how their careers had progressed since the completion of their training. A postal questionnaire was used to gather this information.

Results

These consultants were generally satisfied with their training, and were succeeding in pursuing their careers. Flexible training was developed to enable people with family commitments to train in psychiatry, and this is what it is being used for.

Clinical Implications

Flexible training is an important avenue for an increasing number of psychiatrists to continue in their profession. With the current shortfall in consultant numbers, flexible training should be maintained and developed, and should be seen as a useful route to a consultant position.
Survey of staff attitudes to smoking in a large psychiatric hospital
Authors: Stubbs Jean , Haw Camilla , Garner Liz
Published: June 2004

Aims and Method

The aim of this survey was to examine staff views on smoking at work in a large psychiatric hospital. A postal questionnaire was sent to all clinical staff (n=1471) asking about their smoking habits and attitudes to smoking at work.

Results

The response rate was 40.7%. Overall, 22.0% of respondents were smokers, with unqualified nursing staff having the highest rate (31.0%). The majority of staff did not favour a total ban on smoking by staff, patients or visitors. Smoking habit and profession influenced responses. Smokers and nurses were more permissive in their attitude towards smoking on wards than non-smokers and psychiatrists.

Clinical Implications

Implementation of the government's recommendations on tobacco control in psychiatric units is likely to require considerable preparatory work with staff to ensure full compliance.
Who wants to do psychiatry?
Authors: Yakeley Jessica , Shoenberg Peter , Heady Austin
Published: June 2004

Aims and Method

The study aimed to determine whether medical students who participated in a student psychotherapy scheme aimed at helping them learn about the doctor-patient relationship were more likely to choose psychiatry as a career than a control group who did not participate. One hundred and ninety-eight medical students who participated in the University College and Middlesex School of Medicine (UCMSM) Psychotherapy Scheme between 1982 and 1992, and 200 randomly selected students of the same period who did not, were sent a questionnaire asking about career choice.

Results

Seventy-seven of 163 participants in the scheme who sent back the questionnaire had not thought about doing psychiatry before entering the scheme. Of these, 11 became psychiatrists (14.3%), compared with only two (1.6%) of the 128 controls (of 152 respondents) who had not considered psychiatry as a career at the same stage. This difference is highly significant (P<0.001). Many of the participants, including those who did not specialise in psychiatry, emphasised how the scheme had helped them understand the doctor-patient relationship.

Implications

Participating in the Student Psychotherapy Scheme encouraged medical students to choose psychiatry as a career. This knowledge is important, particularly in view of the current recruitment crisis in psychiatry.
Changing minds at the earliest opportunity
Authors: Shah Nisha
Published: June 2004

Stigmatising attitudes towards mental illness are reinforced by lack of knowledge, and it would seem logical to tackle this from the earliest possible age. A series of talks about mental illness to primary school children were enthusiastically received by the pupils, and revealed that negative attitudes were already present among the older children. The mixed responses of teaching staff supported the idea that increasing awareness of mental illness may have a place in primary education.
Service innovations
Authors: Foster Nicola , Lee Andrew
Published: June 2004

This article describes the establishment of a monthly meeting of a group of psychiatrists and other agencies involved in the delivery of emergency out-of-hours care in general adult and old age psychiatry. The meetings are a source of advice, information, opinion and support regarding on-call issues. The scheme has been running for over 2 years in the Portsmouth area, and has proved to be a valuable educational forum.
Reform of psychiatric services in Germany: hospital staffing directive and commissioning of community care
Authors: Kunze Heinrich , Becker Thomas , Priebe Stefan
Published: June 2004

The German mental health care system differs significantly from the system in the UK. There is no central organisation with overall responsibility as in the National Health Service (NHS), and the government is not entitled to prescribe details of policy or set specific targets. It can only determine the legal framework, define general goals and, with difficulties, influence the spending level. Responsibilities for mental health care, as for other fields of health care, are shared between federal authorities, the 16 states (Lander), local authorities, and semi-statutory organisations, which govern out-patient health care provided by psychiatrists in office-based practices. Virtually every citizen is health-insured and there is free access to health care for those who have no insurance coverage, in which case social services usually cover the costs. Social services also directly fund various services in the community. The fragmented system can be difficult to comprehend. However, many of the challenges are similar to those in other countries, and policy makers and practitioners elsewhere might be interested to know some of the lessons learnt in the German system.
Melatonin in the treatment of insomnia in children and adolescents
Authors: Armour David , Paton Carol
Published: June 2004

Aims and Method

To review the efficacy and safety of melatonin in the treatment of insomnia in children and adolescents, through a Medline search covering the years 1966 to November 2003.

Results

Five placebo-controlled studies and several case series were identified. Melatonin reduces sleep latency, but does not consistently improve other aspects of sleep disturbance. Safety, particularly in the medium- and long-term, is poorly evaluated; short-term concerns include exacerbation of epilepsy and asthma.

Clinical Implications

Melatonin might be effective in the short-term treatment of sleep onset insomnia. The optimal dose is unknown. It cannot currently be recommended for the treatment of other forms of sleep disturbance or for routine long-term use. Melatonin is not a licensed medicine in the UK.
A survey of workplace bullying of psychiatric trainees in the West Midlands
Authors: Hoosen Imthiaz A. , Callaghan Rhiannon
Published: June 2004

Aims and Method

A postal survey was conducted to ascertain the prevalence of bullying behaviour experienced by psychiatric trainees in the West Midlands. Questionnaires were sent to 232 junior doctors, 76% of whom responded.

Results

In the preceding year, 47% of trainees had experienced one or more bullying behaviours. Only 46% reported that they knew whom to contact if they were bullied. Foreign doctors were significantly less likely to take action when bullied than local doctors.

Clinical Implications

Workplace bullying is commonly experienced by psychiatric trainees and other junior doctors in the National Health Service. This behaviour could have adverse effects for both the individual and the employer. To tackle this problem, awareness needs to be raised, and action is required at a number of levels.
Antiapoptotic Effects of Leptin in Human Neuroblastoma Cells
Authors: Russo V. C. , Metaxas S. , Kobayashi K. , Harris M. , Werther G. A.
Published: June 2004

Many factors regulate nervous system development, including complex cross-talk between local neuroendocrine systems. The adipocyte-secreted hormone leptin, mainly known for its key roles in nutrition and reproductive balance, may also be involved in neuroanatomical organization, myelination processes, and neuronal/glia maturation. SK-N-SH-SY5Y neuroblastoma cells were employed as an in vitro model of human neuronal cells to determine whether leptin exerts neuroprotective activities. We show that SH-SY5Y cells express leptin, the long and short isoforms of the leptin receptor (ObRl, ObRs). In SH-SY5Y cells, leptin induced signal transducer and activator of transcription (STAT)-3 phosphorylation and suppressor of cytokine signaling-3 mRNA expression. Leptin dose-dependently increased cell number (up to 200% at 1 μm by 48 h, P < 0.01), and at 24–48 h, leptin at 100 nm increased SH-SY5Y cell number by 30–50%, respectively. SH-SY5Y cell viability was reduced in serum-free conditions at 24 h, and addition of leptin at 100 nm significantly reduced apoptosis by approximately 20% (P < 0.001). Leptin’s antiapoptotic activity required Janus kinase/STAT, MAPK, and phosphatidylinositol-3-kinase activation because the antiapoptotic effects of leptin were abolished, and caspase-3 immunoreactivity increased in the presence of the specific blockers AG490, U0126, or LY294002. Gene array demonstrated that leptin inhibits apoptosis via potent down-regulation of caspase-10 and TNF-related apoptosis-inducing ligand. Our data thus demonstrate, for the first time, that leptin stimulates, in a time- and dose-dependent manner, neuroblastoma cell proliferation and that the underlying mechanisms involve suppression of apoptosis via the Janus kinase-STAT, phosphatidylinositol-3 kinase, and MAPK pathways that culminate altogether in the down-regulation of the apoptotic factors caspase-10 and TNF-related apoptosis-inducing ligand.
Modulation of Ligand Selectivity Associated with Activation of the Transmembrane Region of the Human Follitropin Receptor
Authors: Montanelli Lucia , Van Durme Joost J. J. , Smits Guillaume , Bonomi Marco , Rodien Patrice , Devor Eric J. , Moffat-Wilson Kristin , Pardo Leonardo , Vassart Gilbert , Costagliola Sabine
Published: June 2004

Recently, three naturally occurring mutations in the serpentine region of the FSH receptor (FSHr) (D567N and T449I/A) have been identified in three families with spontaneous ovarian hyperstimulation syndrome (OHSS). All mutant receptors displayed abnormally high sensitivity to human chorionic gonadotropin and, in addition, D567N and T449A displayed concomitant increase in sensitivity to TSH and detectable constitutive activity. In the present study, we have used a combination of site-directed mutagenesis experiments and molecular modeling to explore the mechanisms responsible for the phenotype of the three OHSS FSHr mutants. Our results suggest that all mutations lead to weakening of interhelical locks between transmembrane helix (TM)-VI and TM-III, or TM-VI and TM-VII, which contributes to maintaining the receptor in the inactive state. They also indicate that broadening of the functional specificity of the mutant FSHr constructs is correlated to their increase in constitutive activity. This relation between basal activity and functional specificity is a characteristic of the FSHr, which is not shared by the other glycoprotein hormone receptors. It leads to the interesting suggestion that different pathways have been followed during primate evolution to avoid promiscuous stimulation of the TSHr and FSHr by human chorionic gonadotropin. In the hFSHr, specificity would be exerted both by the ectodomain and the serpentine portion.
Functional Rescue of the Constitutively Internalized V2 Vasopressin Receptor Mutant R137H by the Pharmacological Chaperone Action of SR49059
Authors: Bernier Virginie , Lagacé Monique , Lonergan Michèle , Arthus Marie-Françoise , Bichet Daniel G. , Bouvier Michel
Published: June 2004

In most cases, nephrogenic diabetes insipidus results from mutations in the V2 vasopressin receptor (V2R) gene that cause intracellular retention of improperly folded receptors. We previously reported that cell permeable V2R antagonists act as pharmacological chaperones that rescue folding, trafficking, and function of several V2R mutants. More recently, the vasopressin antagonist, SR49059, was found to be therapeutically active in nephrogenic diabetes insipidus patients. Three of the patients with positive responses harbored the mutation R137H, previously reported to lead to constitutive endocytosis. This raises the possibility that, instead of acting as a pharmacological chaperone by favoring proper maturation of the receptors, SR49059 could mediate its action on R137H V2R by preventing its endocytosis. Here we report that the β-arrestin-mediated constitutive endocytosis of R137H V2R is not affected by SR49059, indicating that the functional rescue observed does not result from a stabilization of the receptor at the cell surface. Moreover, metabolic labeling revealed that R137H V2R is also poorly processed to the mature form. SR49059 treatment significantly improved its maturation and cell surface targeting, indicating that the functional rescue of R137H V2Rs results from the pharmacological chaperone action of the antagonist.
Development of the mammary gland requires DGAT1 expression in stromal and epithelial tissues
Authors: Cases Sylvaine , Zhou Ping , Shillingford Jonathan M. , Wiseman Bryony S. , Fish Jo Dee , Angle Christina S. , Hennighausen Lothar , Werb Zena , Farese Robert V.
Published: June 2004

Mammary gland development is a complex process that is dependent on interactions between the developing mammary epithelium and the surrounding stromal tissues. We show that mice lacking the triglyceride synthesis enzyme acyl CoA:diacylglycerol transferase 1 (DGAT1) have impaired mammary gland development, characterized by decreased epithelial proliferation and alveolar development, and reduced expression of markers of functional differentiation. Transplantation studies demonstrate that the impaired development results from a deficiency of DGAT1 in both the stromal and epithelial tissues. Our findings are the first to link defects in stromal lipid metabolism to impaired mammary gland development.
XenopusStaufen is a component of a ribonucleoprotein complex containing Vg1 RNA and kinesin
Authors: Yoon Young J. , Mowry Kimberly L.
Published: June 2004

RNA localization is a key mechanism for generating cell and developmental polarity in a wide variety of organisms. We have performed studies to investigate a role for the Xenopus homolog of the double-stranded RNA-binding protein, Staufen, in RNA localization during oogenesis. We have found that Xenopus Staufen (XStau) is present in a ribonucleoprotein complex, and associates with both a kinesin motor protein and vegetally localized RNAs Vg1 and VegT. A functional role for XStau was revealed through expression of a dominant-negative version that blocks localization of Vg1 RNA in vivo. Our results suggest a central role for XStau in RNA localization in Xenopus oocytes, and provide evidence that Staufen is a conserved link between specific mRNAs and the RNA localization machinery.
Sox17 and β-catenin cooperate to regulate the transcription of endodermal genes
Authors: Sinner Débora , Rankin Scott , Lee Monica , Zorn Aaron M.
Published: June 2004

Recent studies have led to a model of the molecular pathway that specifies the endoderm during vertebrate gastrulation. The HMG box transcription factor Sox17 is a key component of this pathway and is essential for endoderm formation; however, the molecular events controlled by Sox17 are largely unknown. We have identified several direct transcriptional targets of Sox17,including Foxa1 and Foxa2. We show that β-catenin, a component of Wnt signaling pathway, physically interacts with Sox17 and potentiates its transcriptional activation of target genes. We identify a motif in the C terminus of Sox17, which is conserved in all the SoxF subfamily of Sox proteins, and this motif is required for the ability of Sox17 to both transactivate target genes and bind β-catenin. Nuclear β-catenin is present in endoderm cells of the gastrula, and depletion of β-catenin from embryos results in a repression of Sox17 target genes. These data suggest that in a mechanism analogous to Tcf/Lef interacting with β-catenin,Sox17 and β-catenin interact to transcribe endodermal target genes.
Sperm-triggered [Ca2+] oscillations and Ca2+homeostasis in the mouse egg have an absolute requirement for mitochondrial ATP production
Authors: Dumollard Rémi , Marangos Petros , Fitzharris Greg , Swann Karl , Duchen Michael , Carroll John
Published: June 2004

At fertilisation, repetitive increases in the intracellular Ca2+concentration, [Ca2+]i, drive the completion of meiosis and initiate the development of the quiescent egg into an embryo. Although the requirement for an ATP supply is evident, the relative roles of potential ATP sources remains unclear in the mammalian egg, and the specific role of mitochondria in [Ca2+]i regulation as well as in the sperm-triggered [Ca2+] oscillations is unknown.

We have used fluorescence and luminescence imaging to investigate mitochondrial activity in single mouse eggs. Simultaneous imaging of mitochondrial redox state (NADH and flavoprotein autofluorescence) and[Ca2+]i revealed that sperm-triggered [Ca2+]oscillations are transmitted to the mitochondria where they directly stimulate mitochondrial activity. Inhibition of mitochondrial oxidative phosphorylation caused release of Ca2+ from the endoplasmic reticulum because of local ATP depletion. Mitochondrial ATP production is an absolute requirement for maintaining a low resting [Ca2+]i and for sustaining sperm-triggered [Ca2+] oscillations. Luminescence measurements of intracellular [ATP] from single eggs confirmed that mitochondrial oxidative phosphorylation is the major source of ATP synthesis in the dormant unfertilised egg. These observations show that a high local ATP consumption is balanced by mitochondrial ATP production, and that balance is critically poised. Mitochondrial ATP supply and demand are thus closely coupled in mouse eggs. As mitochondrial ATP generation is essential to sustain the[Ca2+] signals that are crucial to initiate development,mitochondrial integrity is clearly fundamental in sustaining fertility in mammalian eggs.
Presenilin 1 in migration and morphogenesis in the central nervous system
Authors: Louvi Angeliki , Sisodia Sangram S. , Grove Elizabeth A.
Published: June 2004

Morphogenesis of the central nervous system relies in large part upon the correct migration of neuronal cells from birthplace to final position. Two general modes of migration govern CNS morphogenesis: radial, which is mostly glia-guided and topologically relatively simple; and tangential, which often involves complex movement of neurons in more than one direction. We describe the consequences of loss of function of presenilin 1 on these fundamental processes. Previous studies of the central nervous system in presenilin 1 homozygote mutant embryos identified a premature neuronal differentiation that is transient and localized, with cortical dysplasia at later stages. We document widespread effects on CNS morphogenesis that appear strongly linked to defective neuronal migration. Loss of presenilin 1 function perturbs both radial and tangential migration in cerebral cortex, and several tangential migratory pathways in the brainstem. The inability of cells to execute their migratory trajectories affects cortical lamination, formation of the facial branchiomotor nucleus, the spread of cerebellar granule cell precursors to form the external granule layer and development of the pontine nuclei. Finally, overall morphogenesis of the mid-hindbrain region is abnormal,resulting in incomplete midline fusion of the cerebellum and overgrowth of the caudal midbrain. These observations indicate that in the absence of presenilin 1 function, the ability of a cell to move can be severely impaired regardless of its mode of migration, and, at a grosser level, brain morphogenesis is perturbed. Our results demonstrate that presenilin 1 plays a much more important role in brain development than has been assumed, consistent with a pleiotropic involvement of this molecule in cellular signaling.
Transient calnexin interaction confers long-term stability on folded K+ channel protein in the ER
Authors: Khanna Rajesh , Lee Eun Jeon , Papazian Diane M.
Published: June 2004

We recently showed that an unglycosylated form of the Shaker potassium channel protein is retained in the endoplasmic reticulum (ER) and degraded by proteasomes in mammalian cells despite apparently normal folding and assembly. These results suggest that channel proteins with a native structure can be substrates for ER-associated degradation. We have now tested this hypothesis using the wild-type Shaker protein. Wild-type Shaker is degraded by cytoplasmic proteasomes when it is trapped in the ER and prevented from interacting with calnexin. Neither condition alone is sufficient to destabilize the protein. Proteasomal degradation of the wild-type protein is abolished when ER mannosidase I trimming of the core glycan is inhibited. Our results indicate that transient interaction with calnexin provides long-term protection from ER-associated degradation.
Sensitization of Dictyostelium chemotaxis by phosphoinositide-3-kinase-mediated self-organizing signalling patches
Authors: Postma Marten , Roelofs Jeroen , Goedhart Joachim , Loovers Harriët M. , Visser Antonie J. W. G. , Van Haastert Peter J. M.
Published: June 2004

The leading edge of Dictyostelium cells in chemoattractant gradients can be visualized using green fluorescent protein (GFP) tagged to the pleckstrin-homology (PH) domain of cytosolic regulator of adenylyl cyclase (CRAC), which presumable binds phosphatidylinositol-(3,4,5)triphosphate [PtdIns(3,4,5)P3]. Uniform cyclic AMP (cAMP) concentrations induce persistent translocation of PHCrac-GFP from the cytosol to multiple patches, which are similar to the single patch of PHCrac-GFP at the leading edge in a cAMP gradient. We show that cAMP determines the probability of patch formation (half-maximal effect at 0.5 nM cAMP) but not the size, lifetime or intensity of patches, indicating that patches are self-organizing structures. A pseudopod is extended from the area of the cell with a PHCrac-GFP patch at about 10 seconds after patch formation. Cells treated with the F-actin inhibitor latrunculin A are round without pseudopodia; uniform cAMP still induces localized patches of PHCrac-GFP. Inhibition of phosphoinositide-3-kinase (PI3K) activity with LY294002 inhibits PHCrac-GFP patches and inhibits chemotaxis towards nanomolar cAMP but has no effect at higher cAMP concentrations. Thus, very low cAMP concentrations induce self-organizing PHCrac-GFP patches that serve as a spatial cue for pseudopod formation, which enhances the sensitivity and amplitude of chemotactic movement.
Differential localization of the centromere-specific proteins in the major centromeric satellite ofArabidopsis thaliana
Authors: Shibata Fukashi , Murata Minoru
Published: June 2004

The 180 bp family of tandem repetitive sequences, which constitutes the major centromeric satellite in Arabidopsis thaliana, is thought to play important roles in kinetochore assembly. To assess the centromere activities of the 180 bp repeats, we performed indirect fluorescence immunolabeling with antibodies against phosphorylated histone H3 at Ser10, HTR12 (Arabidopsis centromeric histone H3 variant) and AtCENP-C (Arabidopsis CENP-C homologue) for the A. thaliana cell cultures. The immunosignals from all three antibodies appeared on all sites of the 180 bp repeats detected by fluorescence in situ hybridization. However, some of the 180 bp repeat clusters, particularly those that were long or stretched at interphase, were not fully covered with the signals from anti-HTR12 or AtCENP-C. Chromatin fiber immunolabeling clearly revealed that the centromeric proteins examined in this study, localize only at the knobs on the extended chromatin fibers, which form a limited part of the 180 bp clusters. Furthermore, outer HTR12 and inner phosphohistone H3 (Ser10) localization at the kinetochores of metaphase chromosomes suggests that two kinds of histone H3 (a centromere variant and a phosphorylated form) might be linked to different roles in centromere functionality; the former for spindle-fiber attachment, and the latter for chromatid cohesion.
Non-genomic regulation of transmitter release by retinoic acid at developing motoneurons inXenopuscell culture
Authors: Liao Yi-Ping , Ho Shih-Yin , Liou Jau-Cheng
Published: June 2004

Although the long-term effects of all-trans retinoic acid (RA) on neuronal growth and differentiation have been intensively studied, nothing is known about its effect on synaptic transmission. Here we show that RA rapidly and specifically enhances the spontaneous acetylcholine release at developing neuromuscular synapses in Xenopus cell culture using whole-cell patch-clamp recording. Acute addition of RA dose-dependently and reversibly enhances the frequency of spontaneous synaptic currents (SSCs). Application of the lipophilic RA analogue all-trans retinol or RA metabolites produced by light-induced decomposition failed to provoke similar changes in SSC frequency, indicating the specificity of RA-induced facilitation of spontaneous transmitter release. Protein synthesis inhibitors anisomycin or cycloheximide had no effect on RA-induced SSC frequency facilitation. Treating cells with pan RA receptor (RAR) selective agonist or RARβ-selective agonist, but not RARα-, RARγ- or retinoid X receptor (RXR)-selective agonists, mimicked the action of RA. These results suggest that RA acts through the activation of RARβ, to induce a rapid, non-genomic increase in the frequency of spontaneous transmitter release at developing neuromuscular synapses.
Carbohydrates act as sorting determinants in ER-associated degradation of tyrosinase
Authors: Svedine Sherri , Wang Tao , Halaban Ruth , Hebert Daniel N.
Published: June 2004

The endoplasmic reticulum (ER) quality-control machinery maintains the fidelity of the maturation process by sorting aberrant proteins for ER-associated protein degradation (ERAD), a process requiring retrotranslocation from the ER lumen to the cytosol and degradation by the proteasome. Here, we assessed the role of N-linked glycans in ERAD by monitoring the degradation of wild-type (Tyr) and albino mutant (Tyr(C85S)) tyrosinase. Initially, mutant tyrosinase was established as a genuine ERAD substrate using intact melanocyte and semi-permeabilized cell systems. Inhibiting mannose trimming or accumulating Tyr(C85S) in a monoglucosylated form led to its stabilization, supporting a role for lectin chaperones in ER retention and proteasomal degradation. In contrast, ablating the lectin chaperone interactions by preventing glucose trimming caused a rapid disappearance of tyrosinase, initially due to the formation of protein aggregates, which were subsequently degraded by the proteasome. The co-localization of aggregated tyrosinase with protein disulfide isomerase and BiP, but not calnexin, supports an ER organization, which aids in protein maturation and degradation. Based on these studies, we propose a model of tyrosinase degradation in which interactions between N-linked glycans and lectin chaperones help to minimize tyrosinase aggregation and also target non-native substrates for retro-translocation and subsequent degradation.
The nucleolus is involved in mRNA export from the nucleus in fission yeast
Authors: Ideue Takashi , Azad Abul Kalam , Yoshida Jun-ichi , Matsusaka Tadao , Yanagida Mitsuhiro , Ohshima Yasumi , Tani Tokio
Published: June 2004

To elucidate the mechanism of mRNA export from the nucleus, we isolated five novel temperature-sensitive mutants (ptr7 to ptr11) that accumulate poly(A)+ RNA in the nuclei at the nonpermissive temperature in Schizosaccharomyces pombe. Of those, the ptr11 mutation was found in the top2+ gene encoding DNA topoisomerase II. In addition to the nuclear accumulation of poly(A)+ RNA, ptr11 exhibited the cut (cell untimely torn) phenotype at the nonpermissive temperature, like the previously isolated mutant, ptr4. In these two mutants, cytokinesis occurred without prior nuclear division, resulting in cleavage of the undivided nuclei by the septum. To investigate the relationship between mRNA export defects and the cut phenotype observed in ptr4 and ptr11, we analyzed 11 other mutants displaying the cut phenotype and found that all these tested mutants accumulate

poly(A)+ mRNA in the aberrantly cleaved nuclei. Interestingly, nuclear accumulation of poly(A)+ mRNA was observed only in the anucleolate nuclei produced by aberrant cytokinesis. In addition, nuc1, the S. pombe mutant exhibiting a collapsed nucleolus, trapped poly(A)+ mRNA in the nucleolar region at the nonpermissive temperature. In ptr11 and nuc1, mRNA transcribed from the intron-containing TBP gene showed nuclear accumulation, but not transcripts from the intron-less TBP cDNA, suggesting that the export pathway differs between the spliced and unspliced TBP mRNAs. These findings support the notion that a subset of mRNAs in yeast is exported from the nucleus through transient association with the nucleolus.
A NHERF binding site links the βPDGFR to the cytoskeleton and regulates cell spreading and migration
Authors: James Marianne F. , Beauchamp Roberta L. , Manchanda Nitasha , Kazlauskas Andrius , Ramesh Vijaya
Published: June 2004

The Na+/H+ exchanger regulatory factor, NHERF, is a multifunctional adapter protein involved in a wide range of physiological activities. NHERF associates with merlin and the ezrin/radixin/moesin (MERM) family of membrane-actin cytoskeletal linker proteins through its C-terminus and is capable of interacting via its PDZ1 domain to the βPDGF receptor (βPDGFR). Thus, NHERF, potentially links the βPDGFR to the actin cytoskeleton through its interaction with MERM proteins. In the present study, we have examined whether abolishing the interaction of βPDGFR with NHERF results in actin cytoskeletal rearrangements. We have stably expressed a wild-type βPDGFR, a mutant βPDGFR (L1106A) that is incapable of interacting with NHERF, as well as a kinase defective mutant receptor (K634R), in PDGFR-deficient mouse embryonic fibroblasts. Our observations indicate that cells expressing βPDGFR (L1106A) were impaired in their ability to spread and migrate on fibronectin compared with wild-type and K634R cells. L1106A mutant cells also revealed an increased number of focal adhesions, a condensed F-actin ring at the cell periphery and a decrease in total focal adhesion kinase (FAK) tyrosine phosphorylation. Further, we show that NHERF and MERM proteins could act as intermediary bridging proteins between βPDGFR and FAK. Thus, the interaction of βPDGFR with NHERF may provide an essential link between the cell membrane and the cortical actin cytoskeleton independent of receptor activity.
Small Molecular Gelling Agents to Harden Organic Liquids: Trialkyl cis-1,3,5-Cyclohexanetricarboxamides
Authors: Hanabusa Kenji , Kawakami Atsushi , Kimura Mutsumi , Shirai Hirofusa
Published: June 2004

Trialkyl cis-1,3,5-cyclohexanetricarboxamides were able to cause physical gelation in organic liquids to afford completely transparent organogel. The main driving force for gelation was intermolecular hydrogen bonding between amides and van der Waals interaction among hydrophobic alkyl chains.
New Phase Transition Phenomena of DL-2-Amino Butanoic Acid-Water System and DL-Norleucine-Water System
Authors: Matsumoto Masayuki , Yajima Hirofumi , Tezuka Yoshihiko , Ishii Tadahiro , Takahashi Kazuyoshi , Asai Atsushi
Published: June 2004

DSC measurements of transition of DL-2-amino butanoic acid(DL-ABA) and of DL-norleucine(DL-NL) containing water were made. It was found that peak temperature obtained in transition of DL-ABA-water system was independent of water content and was 359 K compared with the B-A transition temperature, 506 K, whereas the peak temperature of DL-NL-water system was nearly equal to 390 K in solid-solid phase transition.
Novel Neutral Anion Ionophores Based on Fluorinated (Poly)Ether Compounds as a Sensory Molecule for an Ion-Selective Electrode
Authors: Siswanta Dwi , Takenaka Jun , Suzuki Takeshi , Sasakura Hideshi , Hisamoto Hideaki , Suzuki Koji
Published: June 2004

Novel neutral anion ionophores based on fluorinated (poly)ether compounds have been synthesized which were first obtained and applied as anion sensory molecules for an ion-selective electrode (ISE).
A Novel Silver-Silica Catalyst Used for the Manufacture of Formaldehyde
Authors: Dai Wei-Lin , Cao Yong , Li He-Xing , Deng Jing-Fa
Published: June 2004

Several novel silver-silica catalysts were prepared by means of sol-gel method, which exhibited high activity and selectivity in the catalytic oxidation of methanol to formaldehyde. The optimum content of silver was determined as 20%(w/w.), which showed 97% conversion and 85.5% yield of formaldehyde. Some other superiority of the as-prepared silver catalysts was observed by comparing with the commercial silver catalysts, including pumice-supported silver and electrolytic silver. XRD patterns reveal that silver is present as a crystalline state in the Ag-SiO2 catalysts.
29Si and 1H NMR of Expandable Mica Ion-exchanged by NH4+
Authors: Noma Hiroaki , Tateyama Hiroshi , Nishimura Satoshi , Inoue Kouzou
Published: June 2004

The 29Si-NMR chemical shift of expandable mica ion-exchanged by NH4+ changes from −95 to −99.5 ppm after heat-treatment at 600 °C, which indicates a change from the mica to a talc structure. The 1H static NMR spectrum of protons remaining in the structure after heating showed a sharp signal with a full width at half maximum of 0.8 kHz at 1.0 ppm, which suggests a rapid proton motion in the structure.
Direct Electrical Communication between the Redox Center of Glucose Oxidase and Electrode via Conductive Polypyrrole Matrix
Authors: Yamada Katsumi , Koizumi Hiroko , Ikeda Koji , Ohkatsu Yasukazu
Published: June 2004

A glucose oxidase (GOD) modified polypyrrole electrode was prepared by coelectropolymerization with unmodified pyrrole. Direct electrical communication between the redox center of GOD and the metal electrode via the conductive polypyrrole matrix was demonstrated using the electrode.
Formation of Singlet Oxygen Photosensitized by Aromatic Amino Acids in Aqueous Solutions
Authors: Shimizu Okiyasu , Watanabe Jun , Imakubo Keiichi , Naito Shizuo
Published: June 2004

Spectral and kinetic evidences are provided for the formation of singlet oxygen photosensitized by aromatic amino acids in air-saturated water. Irradiation of these solutions at 266 nm induces infrared luminescence with a time-resolved spectrum peaking at 1270 nm and a lifetime characteristic of singlet oxygen. In the cases of tryptophan, tyrosine and phenylalanine, the radiative lifetime are 3.3±0.1μs, 3.9±0.1μs and 3.7±0.1μs, respectively.
Spontaneous Formation of Giant Liposomes from Neutral Phospholipids
Authors: Magome Nobuyuki , Takemura Tatsunobu , Yoshikawa Kenichi
Published: June 2004

Giant liposomes were formed spontaneously from neutral phospholipids in an aqueous solution containing MgCl2. Based on both dark-field microscopy and transmission electron microscopy, we concluded that these giant liposomes are unilamellar.
Prediction of Selectivity Coefficients of Medicine Electrode Using Artificial Neural Networks and Partial Least Squares
Authors: Xing Wan-Li , Zhang Chun-Xun , He Xi-Wen
Published: June 2004

In this paper, the selectivity coefficient of ion selective electrode is first predicted by artificial neural networks (ANN) and partial least squares (PLS), with topological indices of the interference taken as inputs for these two chemometric techniques. The prediction results for ANN were better than that of PLS.
Electropolymerization of Two-Dimensional Polypyrrole with Fractal Patterns under a Mica
Authors: Shan Jingning , Yuan Chunwei , Zhang Haiqian
Published: June 2004

With the needle-circle elctrode configuration, two-dimensional(2-D) Polypyrrole(PPy) with a fractal pattern was electropolymerized under a mica which was set on the electrolyte solution surface. The mica serves as a sample of the induction substrate to support the growth of PPy. The results provide a new way to obtain 2-D PPy and have prospect in research and practice.
Molecular Self-Organization of Liquid Crystals through the Formation of Hydrogen-Bonded Networks among a Mesogenic Diol and Imidazoles
Authors: Kato Takashi , Kawakami Taihei
Published: June 2004

A new class of liquid-crystalline materials consisting of a mesogenic diol and imidazoles exhibits stable smectic liquid-crystalline phases by self-organization through the formation of hetero-intermolecular hydrogen-bonded networks.
Complexation and Crystallization of Rare Earth Salts in DEG and TEG
Authors: Ohno Hiroyuki , Saito Yoshihiro , Yamase Toshihiro
Published: June 2004

Solubility of a series of rare earth salts (LnCl3·6H2O; Ln=La, Ce, Pr, Nd, Sm, Gd, Dy, Er and Yb) was studied in diethylene glycol (DEG) and triethylene glycol (TEG). Almost all rare earth salts were dissolved in TEG and room temperature, and they were separated out as crystals by heating. Against this, their solubility in DEG depended on the atomic number (number of electrons in f-orbital). Crystals grew after heating in DEG. The crystal obtained from DEG solution of NdCl3·6H2O was analyzed with X-ray crystallography. It was anhydrous crystal and one Nd3+ cation was revealed to be solvated with nine oxygen atoms of three DEG molecules.
Preparation of Novel Biodegradable Polyampholyte: Partially Dicarboxylated Chitosan
Authors: Matsumura Shuichi , Yokochi Eiji , Winursito Isananto , Toshima Kazunobu
Published: June 2004

Amphoteric and biodegradable polycarboxylates having a varying amount of unreacted glucosamine moieties as the biologically active group as well as the biodegradable moiety were prepared by the partial oxidation of chitosan using sodium periodate at pH 3.0 followed by oxidation with sodium chlorite. Partially dicarboxylated chitosan containing more than about 50% unreached glucosamine residue showed good biodegradation using activated sludge for 28 days.
Size Growth Factor in the Process of Vesicle Formation from Phospholipid-Detergent Mixed Micelles
Authors: Ueno Masaharu , Kashiwagi Hiroshi , Hirota Noriko
Published: June 2004

Small unilamellar vesicles (SUV*) appeared in the transition region were reproduced by adding proper amount of detergent to SUV prepared by ultrasonication. It was found that SUV* are fusible to grow their size time-dependently resulting in formation of large unilamellar vesicles (LUV) if octylglucoside was used as a detergent, but are not if sodium cholate was used. On the basis above results it was discussed that post-vesiculation size growth is a crucial factor to regulate vesicle size in the process of vesicle formation from detergent-phospholipid mixed micelles.
Thermosensitive Copolymers of N-(2-Hydroxypropyl)methacrylamide and Alkyl Methacrylates
Authors: Sugiyama Kazuo , Mitsuno Satoshi , Yasufuku Yoshihiro , Shiraishi Kohei
Published: June 2004

The aqueous solution of copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) and alkyl methacrylate (RMA, alkyl : methyl or butyl) with molar ratio of RMA more than 0.08 was found to exhibit the LCST though no phase transition occurred for the case of the homopolymer of HPMA.
1,4-Asymmetric Induction in Palladium(II)-catalyzed Intramolecular N-Alkylation Reaction. Construction of 2-Functionalized 5- Hydroxypiperidine
Authors: Hirai Yoshiro , Shibuya Kaori , Fukuda Yoko , Yokoyama Hajime , Yamaguchi Seiji
Published: June 2004

Palladium(II)-catalyzed cyclization of optically active urethanes containing an allylic alcohol moiety was examined. Efficient 1,4-asymmetric induction was found in this reaction. The cycloadducts were converted to pseudoconhydrine.
Solvent-Dependent Quenching of the Lowest Excited Singlet State of 9,10-Dichloroanthracene by Ground-State 2,5-Dimethylhexa-2,4-diene Yielding 9-Chloroanthracene in Acetonitrile or the [4+2] Adduct in n-Heptane
Authors: Nakayama Toshihiro , Amijima Yutaka , Miki Sadao , Hamanoue Kumao
Published: June 2004

In acetonitrile, an exciplex formed between the lowest excited singlet state (1DCA*) of 9,10-dichloroanthracene (DCA) and ground-state 2,5-dimethylhexa-2,4-diene (DMHD) generates the DCA radical anion as an intermediate for dechlorination of DCA yielding 9-chloroanthracene. In n-heptane, however, quenching of 1DCA* by DMHD forms no exciplex and a dibenzobicyclo[2.2.2]octadiene-type compound (the [4+2] adduct) is obtained as the final product.
Two Alkyl Resorcarenes as New Stationary Phases for Isomer Separation by GC
Authors: Zhang Hanbang , Ling Yun , Dai Rongji , Wen Yuxiu , Fu Ruonong , Gu Junling
Published: June 2004

Two resorcarene derivatives were synthesized and used as a new kind of capillary gas chromatography stationary phase. The results showed that they have high efficiency, medium polarity and excellent selectivity for isomers of industrial chemicals such as substituted benzenes. In the separation of naphthalene and analogs, the strong retention ability was observed. The thermal stability of the new stationary phases are approximately 240 °C.
Simultaneous Determination of Sodium(I) and Potassium(I) by Adsorption Voltammetry
Authors: Huang Hailan , Wang Lizeng , Ma Chengsong , Zhang Xiaoli , Liu Chengxia
Published: June 2004

In 0.05mol/dm3 tetrabutylammonium iodide (Dimethylformamide as solvent) buffer solution (pH=4.5), the reduction peaks of Na+ and K+ are very close. After dibenzo-18-crown-6 is added in, K+ may form complex with it. The complex can be reduced at the hanging mercury drop electrode, and gives a new reductive peak at −1.80 V which is more negative than the reductive peak of Na+. The peak current of the two peaks are proportional to the concentration of Na+ and K+ in the range of 1.0×10−8∼1.0×10−6 mol/dm3 and 2.0×10−9∼4.0×10−6 mol/dm3 respectively. The detection limits are 5.0×10−9 mol/dm3 and 6.0×10−10 mol/dm3 separately. The proposed method has been applied to the determination of Na+ and K+ content in banana and its peel.