bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of C‐terminus of Kir7.1 potassium channel in cell‐surface expression
Authors: Tateno Toru , Nakamura Nobuhiro , Hirata Yukio , Hirose Shigehisa 
Published: January 2006

AbstractInward rectifier K+channel Kir7.1 is predominantly expressed on the plasma membrane of a variety of ion‐transporting epithelia. The electrophysiological property of Kir7.1 has been well characterized but the mechanism underlying the plasma‐membrane targeting remains elusive. To address this issue, we examined the effect of deletion and site‐directed mutagenesis on the plasma‐membrane localization of Kir7.1 in Madin‐Darby canine kidney cells by immunofluorescence microscopy and cell‐surface biotinylation. Although deletions of up to 37 amino acid residues from the C‐terminus had no effect, further deletion resulted in accumulation of the mutant proteins in intracellular membranes. No sequence motif for subcellular targeting was found in the distal C‐terminal region. The cell‐surface expression of the deletion mutant lacking 38 or 40 C‐terminal residues was restored by addition of one or three alanine residues, respectively, to the C‐terminus end. These results suggest that the C‐terminal length plays an important role in the plasma‐membrane localization of Kir7.1.
Effects of scallop dredging on macrobenthic communities in west Iceland
Authors: Guijarro Garcia Elena , Ragnarsson Stefán Áki , Eiríksson Hrafnkell 
Published: January 2006

Abstract
Effects of scallop dredging on benthic communities in Breidafjordur, west Iceland, were investigated by analysing bycatch data from scallop stock assessment surveys and effort data from the commercial scallop fishery. Bycatch constituted 28% of the total catch, with eight benthic macrofaunal taxa alone making up nearly 98% of the bycatch. Modiolus modiolus and Cucumaria frondosa dominated in terms of abundance and biomass in most of the study area regardless of intensity of fishing effort, although both have been identified as sensitive to fishing in other studies. The macrofaunal benthic community in Breidafjordur consisted mostly of hard-shelled molluscs, holothurians, crabs, and starfish. Emerging epifauna was absent in the samples taken since 1993. These results suggest that our study was carried out within an already altered community that would have suffered the greatest impact during the early years of the scallop fishery. However, the available data are not enough to endorse this assumption with complete certainty.
Impaired verbal self-monitoring in psychosis: effects of state, trait and diagnosis
Authors: JOHNS LOUISE C. , GREGG LYNSEY , ALLEN PAUL , McGUIRE PHILIP K. 
Published: January 2006

Background. Cognitive models propose that auditory verbal hallucinations arise through defective self-monitoring and external attribution of inner speech. We used a paradigm that engages verbal self-monitoring to examine how deficits in this process are related to symptoms and diagnosis in patients with psychosis.Method. We tested 45 patients with schizophrenia. Fifteen had current auditory hallucinations, 15 had a history of (but no current) auditory hallucinations, and 15 had delusions but neither current nor previous hallucinations. We also tested 10 patients with affective psychosis and current auditory hallucinations, and 20 healthy volunteers. Participants read single adjectives aloud while the source and the pitch of the on-line auditory verbal feedback was manipulated, then immediately identified the source of the speech they heard (‘self’/‘other’/‘unsure’).Results. When reading aloud with distorted feedback of their own voice, patients with schizophrenia who had auditory hallucinations were more likely than controls to misidentify its source as ‘other’. Patients with delusions but no current hallucinations displayed a similar deficit, although there was a trend for this to be less marked. Patients with a history of hallucinations did not differ from controls. Patients with hallucinations in the context of an affective disorder made more unsure responses rather than misattributions.Conclusions. Difficulty with source monitoring was related to the acute psychotic state rather than a predisposition to hallucinations, and was evident in patients with affective psychosis as well as schizophrenia. External misattribution of source may reflect an impairment in verbal self-monitoring and/or the appraisal of ambiguous sensory material.
Thought disorder in schizophrenia is associated with both executive dysfunction and circumscribed impairments in semantic function
Authors: STIRLING JOHN , HELLEWELL JONATHAN , BLAKEY ANDREW , DEAKIN WILLIAM 
Published: January 2006

Background. Formal thought disorder (FTD) has long been regarded as a key sign of schizophrenia but little is known about its origins or aetiology. One suggestion is that it is directly related to disordered language functioning; a second is that it is a reflection of poor neurocognitive functioning. A current model posits that it is related to a combination of executive dysfunction and impaired semantic processing.Method. To examine these alternative ideas, a heterogeneous group of 30 patients, all carrying a diagnosis of schizophrenia, and 18 non-patient controls completed a series of neurocognitive and psycholinguistic tests, and a clinical review that, inter alia, permitted assessment of thought disorder (TD) using the Thought, Language and Communication Scale (TLC).Results. Patients generally performed at a lower level on most components of the test battery, but there was little evidence of a relationship between TD and syntactic psycholinguistic function. However, schizophrenic patients manifesting higher levels of TD performed at a lower level on tests sensitive to executive dysfunction and semantic impairments.Conclusions. The origins of TD seem more closely linked to deficits in executive functioning and semantic processing than to impairments in other language functions or general cognition.
Incremental cost-effectiveness of a collaborative care intervention for panic disorder
Authors: KATON WAYNE , RUSSO JOAN , SHERBOURNE CATHY , B. STEIN MURRAY , CRASKE MICHELLE , FAN MING-YU , ROY-BYRNE PETER 
Published: January 2006

Background. Panic disorder is a prevalent, often disabling, disorder among primary-care patients, but there are large gaps in quality of treatment in primary care. This study describes the incremental cost-effectiveness of a combined cognitive behavioral therapy (CBT) and pharmacotherapy intervention for patients with panic disorder versus usual primary-care treatment.Method. This randomized control trial recruited 232 primary-care patients meeting DSM-IV criteria for panic disorder from March 2000 to March 2002 from six primary-care clinics from university-affiliated clinics at the University of Washington (Seattle) and University of California (Los Angeles and San Diego). Patients were randomly assigned to receive either treatment as usual or a combined CBT and pharmacotherapy intervention for panic disorder delivered in primary care by a mental health therapist. Intervention patients had up to six sessions of CBT modified for the primary-care setting in the first 12 weeks, and up to six telephone follow-ups over the next 9 months. The primary outcome variables were total out-patient costs, anxiety-free days (AFDs) and quality adjusted life-years (QALYs).Results. Relative to usual care, intervention patients experienced 60·4 [95% confidence interval (CI) 42·9–77·9] more AFDs over a 12-month period. Total incremental out-patient costs were $492 higher (95% CI $236–747) in intervention versus usual care patients with a cost per additional AFD of $8.40 (95% CI $2.80–14.0) and a cost per QALY ranging from $14158 (95% CI $6791–21496) to $24776 (95% CI $11885–37618). The cost per QALY estimate is well within the range of other commonly accepted medical interventions such as statin use and treatment of hypertension.Conclusions. The combined CBT and pharmacotherapy intervention was associated with a robust clinical improvement compared to usual care with a moderate increase in ambulatory costs.
Evidence that the outcome of developmental expression of psychosis is worse for adolescents growing up in an urban environment
Authors: SPAUWEN JANNEKE , KRABBENDAM LYDIA , LIEB ROSELIND , WITTCHEN HANS-ULRICH , VAN OS JIM 
Published: January 2006

Background. The urban environment may increase the risk for psychotic disorder in interaction with pre-existing risk for psychosis, but direct confirmation has been lacking. The hypothesis was examined that the outcome of subclinical expression of psychosis during adolescence, as an indicator of psychosis-proneness, would be worse for those growing up in an urban environment, in terms of having a greater probability of psychosis persistence over a 3·5-year period.Method. A cohort of 918 adolescents from the Early Developmental Stages of Psychopathology Study (EDSP), aged 14–17 years (mean 15·1 years), growing up in contrasting urban and non-urban environments, completed a self-report measure of psychotic symptoms at baseline (Baseline Psychosis) and at first follow-up around 1 year post-baseline (T1). They were again interviewed by trained psychologists for the presence of psychotic symptoms at the second follow-up on average 3·5 years post-baseline (T2).Results. The rate of T2 psychotic symptoms was 14·2% in those exposed to neither Baseline Psychosis nor Urbanicity, 12·1% in those exposed to Urbanicity alone, 14·9% in those exposed to Baseline Psychosis alone and 29·0% in those exposed to both Baseline Psychosis and Urbanicity. The odds ratio (OR) for the combined exposure was 2·46 [95% confidence interval (CI) 1·46–4·14], significantly greater than that expected if Urbanicity and Baseline Psychosis acted independently.Conclusion. These findings support the suggestion that the outcome of the developmental expression of psychosis is worse in urban environments. The environment may impact on risk for psychotic disorder by causing an abnormal persistence of a developmentally common expression of psychotic experiences.
INTERNATIONAL AID: WHEN GIVING BECOMES A VICE
Authors: Badhwar Neera K. 
Published: January 2006

Peter Singer and Peter Unger argue that moral decency requires giving
away all one's “surplus” for the relief or prevention of “absolute poverty,”
because not doing so is analogous to refusing to save a drowning child to
avoid making one's clothes muddy.
I argue that there is a crucial disanalogy between the two cases and,
moreover, that there are four independent moral objections to their thesis:
it is monomaniacal in ignoring the variety of morally worthy ideals and
elevating self-sacrificial aid to the global poor into the sole ideal; it is
misanthropic in its indifference to the happiness of those it adjures to
give; it is incompatible with integrity; it would have disastrous effects
for the poor if it were generally adopted. I argue that genuine beneficence
aims at creating or restoring the conditions that enable its beneficiaries
to become self-sufficient creators themselves — creators of wealth and of
meaningful and enjoyable lives. Small-scale beneficence is necessary for
moral goodness, but large-scale beneficence is optional, so long as its
absence is not due to a lack of regard for those in need. The uncharitable
person violates the neo-Lockean non-waste proviso that we acquire or keep
for ourselves and those we love as much, but only as much, as we can use or
invest meaningfully or enjoyably, now or in the long run. But someone who
invests all his resources in creating something of worth leads a morally
worthy life even if he reserves nothing for large-scale charity. Both our
capacity for beneficence, which bids us stretch out a hand to those in need,
and our capacity for creation, which bids us reach for the stars, are
important aspects of our humanity. The Singer-Unger ideal advocates not
genuine beneficence but the profligate giving away of wealth to prolong
lives, while failing to appreciate what makes life worth living.
RESPONSIBILITY AND GLOBAL JUSTICE: A SOCIAL CONNECTION MODEL
Authors: Young Iris Marion 
Published: January 2006

The essay theorizes the responsibilities moral agents may be said to
have in relation to global structural social processes that have unjust
consequences. How ought moral agents, whether individual or institutional,
conceptualize their responsibilities in relation to global injustice? I
propose a model of responsibility from social connection as an
interpretation of obligations of justice arising from structural social
processes. I use the example of justice in transnational processes of
production, distribution and marketing of clothing to illustrate operations
of structural social processes that extend widely across regions of the
world.
The social connection model of responsibility says that all agents who
contribute by their actions to the structural processes that produce
injustice have responsibilities to work to remedy these injustices. I
distinguish this model from a more standard model of responsibility, which I
call a liability model. I specify five features of the social connection
model of responsibility that distinguish it from the liability model: it
does not isolate perpetrators; it judges background conditions of action; it
is more forward looking than backward looking; its responsibility is
essentially shared; and it can be discharged only through collective action.
The final section of the essay begins to articulate parameters of reasoning
that agents can use for thinking about their own action in relation to
structural injustice.
The role of inflammation in CNS injury and disease
Authors: Lucas Sian‐Marie , Rothwell Nancy J , Gibson Rosemary M 
Published: January 2006

For many years, the central nervous system (CNS) was considered to be ‘immune privileged’, neither susceptible to nor contributing to inflammation. It is now appreciated that the CNS does exhibit features of inflammation, and in response to injury, infection or disease, resident CNS cells generate inflammatory mediators, including proinflammatory cytokines, prostaglandins, free radicals and complement, which in turn induce chemokines and adhesion molecules, recruit immune cells, and activate glial cells. Much of the key evidence demonstrating that inflammation and inflammatory mediators contribute to acute, chronic and psychiatric CNS disorders is summarised in this review. However, inflammatory mediators may have dual roles, with detrimental acute effects but beneficial effects in long‐term repair and recovery, leading to complications in their application as novel therapies. These may be avoided in acute diseases in which treatment administration might be relatively short‐term. Targeting interleukin (IL)‐1 is a promising novel therapy for stroke and traumatic brain injury, the naturally occurring antagonist (IL‐1ra) being well tolerated by rheumatoid arthritis patients. Chronic disorders represent a greater therapeutic challenge, a problem highlighted in Alzheimer's disease (AD); significant data suggested that anti‐inflammatory agents might reduce the probability of developing AD, or slow its progression, but prospective clinical trials of nonsteroidal anti‐inflammatory drugs or cyclooxygenase inhibitors have been disappointing. The complex interplay between inflammatory mediators, ageing, genetic background, and environmental factors may ultimately regulate the outcome of acute CNS injury and progression of chronic neurodegeneration, and be critical for development of effective therapies for CNS diseases.British Journal of Pharmacology (2006) 147, S232–S240. doi:10.1038/sj.bjp.0706400
Cannabinoid pharmacology: the first 66 years
Authors: Pertwee Roger G 
Published: January 2006

Research into the pharmacology of individual cannabinoids that began in the 1940s, several decades after the presence of a cannabinoid was first detected in cannabis, is concisely reviewed. Also described is how this pharmacological research led to the discovery of cannabinoid CB1 and CB2 receptors and of endogenous ligands for these receptors, to the development of CB1‐ and CB2‐selective agonists and antagonists and to the realization that the endogenous cannabinoid system has significant roles in both health and disease, and that drugs which mimic, augment or block the actions of endogenously released cannabinoids must have important therapeutic applications. Some goals for future research are identified.British Journal of Pharmacology (2006) 147, S163–S171. doi:10.1038/sj.bjp.0706406
Neuropharmacology of 5‐hydroxytryptamine
Authors: Richard Green A 
Published: January 2006

This review outlines the history of our knowledge of the neuropharmacology of 5‐hydroxytryptamine (5‐HT; serotonin), focusing primarily on the work of U.K. scientists. The existence of a vasoconstrictive substance in the blood has been known for over 135 years. The substance was named serotonin and finally identified as 5‐HT in 1949. The presence of 5‐HT in the brain was reported by Gaddum in 1954 and it was Gaddum who also demonstrated that the action of 5‐HT (in the gut) was antagonised by the potent hallucinogen lysergic acid diethylamide. This provoked the notion that 5‐HT played a pivotal role in the control of mood and subsequent investigations have generally confirmed this hypothesis. Over the last 50 years a good understanding has been gained of the mechanisms involved in control of the storage, synthesis and degradation of 5‐HT in the brain. Knowledge has also been gained on control of the functional activity of this monoamine, often by the use of behavioural models. A considerable literature also now exists on the mechanisms by which many of the drugs used to treat psychiatric illness alter the functional activity of 5‐HT, particularly the drugs used to treat depression. Over the last 20 years the number of identified 5‐HT receptor subtypes has increased from 2 to 14, or possibly more. A major challenge now is to utilise this knowledge to develop receptor‐specific drugs and use the information gained to better treat central nervous system disorders.British Journal of Pharmacology (2006) 147, S145–S152. doi:10.1038/sj.bjp.0706427
Neurotransmitter transporters and their impact on the development of psychopharmacology
Authors: Iversen Leslie 
Published: January 2006

The synaptic actions of most neurotransmitters are inactivated by reuptake into the nerve terminals from which they are released, or by uptake into adjacent cells. A family of more than 20 transporter proteins is involved. In addition to the plasma membrane transporters, vesicular transporters in the membranes of neurotransmitter storage vesicles are responsible for maintaining vesicle stores and facilitating exocytotic neurotransmitter release. The cell membrane monoamine transporters are important targets for CNS drugs. The transporters for noradrenaline and serotonin are key targets for antidepressant drugs. Both noradrenaline‐selective and serotonin‐selective reuptake inhibitors are effective against major depression and a range of other psychiatric illnesses. As the newer drugs are safer in overdose than the first‐generation tricyclic antidepressants, their use has greatly expanded. The dopamine transporter (DAT) is a key target for amphetamine and methylphenidate, used in the treatment of attention deficit hyperactivity disorder. Psychostimulant drugs of abuse (amphetamines and cocaine) also target DAT. The amino‐acid neurotransmitters are inactivated by other families of neurotransmitter transporters, mainly located on astrocytes and other non‐neural cells. Although there are many different transporters involved (four for GABA; two for glycine/D‐serine; five forL‐glutamate), pharmacology is less well developed in this area. So far, only one new amino‐acid transporter‐related drug has become available: the GABA uptake inhibitor tiagabine as a novel antiepileptic agent.British Journal of Pharmacology(2006)147, S82–S88. doi:10.1038/sj.bjp.0706428
Purinergic signalling
Authors: Burnstock Geoffrey 
Published: January 2006

While there were early papers about the extracellular actions of purines, the role of ATP as a purinergic neurotransmitter in nonadrenergic, noncholinergic nerves in the gut and bladder in 1972 was a landmark discovery, although it met considerable resistance for the next 20 years. In the early 1990s, receptors for purines were cloned: four P1 receptor subtypes and seven P2X ionotropic and eight P2Y metabotropic receptor subtypes are currently recognized and characterized. The mechanisms underlying ATP release and breakdown are discussed. Purines and pyrimidines have major roles in the activities of non‐neuronal cells as well as neurons. This includes fast signalling roles in exocrine and endocrine secretion, platelet aggregation, vascular endothelial cell‐mediated vasodilation and nociceptive mechanosensory transduction, as well as acting as a cotransmitter and neuromodulator in most, if not all, nerve types in the peripheral and central nervous systems. More recently, slow (trophic) purinergic signalling has been implicated in cell proliferation, migration, differentiation and death in embryological development, wound healing, restenosis, atherosclerosis, ischaemia, cell turnover of epithelial cells in skin and visceral organs, inflammation, neuroprotection and cancer.British Journal of Pharmacology(2006)147, S172–S187. doi:10.1038/sj.bjp.0706429
75 years of opioid research: the exciting but vain quest for the Holy Grail
Authors: Corbett Alistair D , Henderson Graeme , McKnight Alexander T , Paterson Stewart J 
Published: January 2006

Over the 75‐year lifetime of the British Pharmacological Society there has been an enormous expansion in our understanding of how opioid drugs act on the nervous system, with much of this effort aimed at developing powerful analgesic drugs devoid of the side effects associated with morphine – the Holy Grail of opioid research. At the molecular and cellular level multiple opioid receptors have been cloned and characterised, their potential for oligomerisation determined, a large family of endogenous opioid agonists has been discovered, multiple second messengers identified and our understanding of the adaptive changes to prolonged exposure to opioid drugs (tolerance and physical dependence) enhanced. In addition, we now have greater understanding of the processes by which opioids produce the euphoria that gives rise to the intense craving for these drugs in opioid addicts. In this article, we review the historical pathway of opioid research that has led to our current state of knowledge.British Journal of Pharmacology(2006)147, S153–S162. doi:10.1038/sj.bjp.0706435