bluuebunny/crossref_metadata_2025 huggingface dataset:
Aboriginal Right: A Conciliatory Concept
Authors: MORITO BRUCE
Published: February 2008

The confusion that persists over Aboriginal claim in North America calls for close examination. The paper begins by sorting out various versions of ‘Aboriginal right’and some of the main factors that govern its use. Confusion is analysed as the result of conflating different frames of reference which determine different sets of expectations by Aboriginal and government representatives.

To appreciate the significance of this conflation, it is helpful if not necessary to view the move to use the concept ‘Aboriginal right’as a strategic rather than a legally substantive one. Understanding the move in this way helps to explain why it is that definitions remain elusive. The effect of using the concept has indeed been to enable Aboriginals finally and effectively to table their claim. However, the strategy has its cost. Using the language of the courts places Aboriginal negotiators at a disadvantage, since that language is ineluctably tied to European social and legal sensibilities that militate against understanding Aboriginal claim.

If, in the end, we understand that the move to use the language of the courts has been conciliatory, we can better recognise the nature of Aboriginal claim. We can begin to understand that it involves a complex web of responsibilities and commitments, most of which have either been forgotten or perverted to suit government agendas. We can begin to see that it has to do with restoring a relationship of mutual respect and protection.
Warren, Plumwood, a Rock and a Snake: Some Doubts about Critical Ecological Feminism
Authors: ANDREWS JOHN
Published: February 2008

In this paper I expound and criticise the arguments of two leading exponents of critical ecological feminism. According to critical ecological feminism responsibility for the oppressions of the natural world and the oppressions of racism and sexism can be traced to a logic of domination that is based on suspect value dualities and presupposes an unacceptable ‘moral extensionism’(the view that moral status depends on membership of a specified class). I argue firstly that critical ecological feminism's critique of value dualism presupposes the truth of the thesis that humans and non‐humans are morally equal, a thesis for which it offers no persuasive arguments (indeed critical ecological feminism advocates a kind of virtue ethic which is itself incompatible with such supposed equality). Secondly I maintain that moral extensionism, contrary to the claims of critical ecological feminism, can support a genuine respect for the natural world. Finally I suggest that the arguments for one version of critical ecological feminism, in order to be made convincing, themselves require the truth of moral extensionism.
Who Benefits?— Why personal identity does not matter in a moral evaluation of germ‐line gene therapy
Authors: HOLTUG NILS , SANDØE PETER
Published: February 2008

Recently it has been argued that some instances of germ‐line gene therapy will change the identity of the person who receives the benefit of therapy, and that in these instances there is no good moral reason to conduct germ‐line gene therapy. Against this we argue that even if gene therapy should have an effect on the identity of the resulting person, this would not diminish the urgency of the therapy. Not only would impersonal moral reasons speak in favour of such radical gene therapy, there would also be person‐affecting reasons to perform it.
On Reasonableness
Authors: MOORE MARGARET
Published: February 2008

This essay argues that the concept of ‘reasonableness’plays an important role in Scanlon's, Rawls's, and Barry's theories of justice (or morality). The relationship between moral motivation and reasonableness is critically analysed. Specifically, the paper questions whether it is plausible to impute to the agents of construction the desire ‘to justify our actions to others on impartial terms’. It also argues that most of the work is done by the assumption that people are reasonable rather than by the contractarian formulation. Indeed, the paper argues, the argument could proceed entirely by making explicit and arguing for the moral assumptions embedded in the concept of reasonableness [1].
Tackling Crime by Other Means
Authors: LUKE ANDREW
Published: February 2008

If crime is a social problem, then ways of preventing it must be sought. Punishment has been the traditional approach to preventing crime, either as a deterrent, or as a means of reforming the offender. Neither of these approaches is wholly acceptable. Even if deterrence punishment, as grounded in utilitarianism, effectively prevents crime, there may be other methods which produce better results. Reform fails to justify any form of punishment since not only does punishment not reform, but it interferes with the reformative process. Reform is limited in scope to those people who commit crimes and are caught. If crime is to be prevented, then it is necessary to go beyond the crime and the criminal and consider the social contexts in which people act, and the ways in which they learn to react to them. By shaping both the environment and people's responses to it, society can solve the problem of preventing crime, without the need for punishment.
The Value of Truth and the Care of the Soul
Authors: WITHERALL ARTHUR
Published: February 2008

Although the argument against the neo‐Darwinian theory of evolution presented by Stephen R. L. Clark in From Athens to Jerusalem is based upon sound principles, it fails to provide an a priori refutation. If it did work, it would refute all objective scientific theories, since all of them make consciousness and subjectivity, as Clark characterises them, incomprehensible. Scientism, the thesis that science is the only source of truth, is Clark's real target, rather than science per se, but he does not diagnose this error as it is made by authors such as Jacques Monod and Richard Dawkins. Scientism is not essential to materialism in general, and a successful version of ‘supervenience‐materialism’could avoid both reductionism and scientism. However, Clark still has a reply. He may use his discussion of the value of truth to provide a more general critique of materialism, which in my view is far more effective.
On Making and Keeping Promises
Authors: FOX RICHARD M. , DeMARCO JOSEPH P.
Published: February 2008

Do the conditions under which promises are made determine whether they ought to be kept? Philosophers have placed a number of conditions on promising which, they hold, must be met in order to make promise‐keeping obligatory. In so doing, they have distinguished valid promises from invalid promises and justified promises from promises that are not justified. Considering such conditions, one by one, we argue that they are mistaken. In the first place, the conditions they lay down are not necessary for either valid or justified promise‐making. In the second place, promises need not meet such conditions in order to create moral obligations. In general, such analyses of promising fail because they suffer from a confusion between promise‐making and promise‐keeping. Philosophers have wrongly supposed that obligations to keep promises are dependent upon, or derivable from, the quality of the promises themselves, at the time they are made, instead of focusing on conditions that must be satisfied at the time when promises are supposed to be kept. It is not the quality of a promise that determines an obligation to keep it but the rightness or wrongness of performing the promised act.
On Applying Applied Philosophy
Authors: DOWNING F. GERALD
Published: February 2008

If ‘applied philosophy’is really to be applied it is necessary for its practical implications to be spelled out in some detail: both the specific goals implied if not entailed, and the life‐style that would be expected to support such goals. To be as specific as this would only be to emulate the ancient Greek philosophers whose influence may still be discerned and is often claimed. Contributions to a recent issue of this Journal are taken as a basis for the discussion.
Should Nationalists be Communitarians?
Authors: ARCHARD DAVID
Published: February 2008

John O'Neill argues in a recent article, ‘Should Communitarians be Nationalists?’, that communitarians are wrong to be committed to the defence of ties of nationhood, both because the nation‐state's rise is associated with the disappearance of the ties of community and because the nation is an illusory community. I argue that the evidence that communitarianism is committed as charged to the defence of nationality is unconvincing. Further, the familiar accusation that the nation is a false or unreal community is neither perspicuous nor obviously true. It is important to evaluate the significance and worth of the nation as a community independently of the nationalist prescription that the nation and the state should coincide. The important question is not whether the political community should be a nation, but what sort of community the nation should be.
Milgram, Method and Morality
Authors: PIGDEN CHARLES R. , GILLET GRANT R.
Published: February 2008

In Milgram's experiments, subjects were induced to inflict what they believed to be electric shocks in obedience to a man in a white coat. This suggests that many can be persuaded to torture, and perhaps kill, another person simply on the say‐so of an authority figure. But the experiments have been attacked on methodological, moral and methodologico‐moral grounds. Patten argues that the subjects probably were not taken in by the charade; Bok argues that lies should not be used in research; and Patten insists that any excuse for Milgram's conduct can be adapted on behalf of his subjects. (Either he was wrong to conduct the experiments or they do not establish the phenomenon of immoral obedience). We argue that the subjects were indeed taken in, that lies (though usually wrong) were in this case legitimate, and that there were excuses available to Milgram which were not available to his subjects. So far from ‘disrespecting’his subjects, Milgram enhanced their autonomy as rational agents. We concede however that it might be right to prohibit what it was right to do. [1]
Directed Evolution
Authors: VAN EYKEN ALBERT
Published: February 2008

Though we humans are immensely more gifted than other animals, yet we are not the outcome of an inevitable selection of the ‘fittest’. Nor on the other hand is our importance diminished by our evolutionary inheritance. Besides, we are already here! Faith in inevitable progress is a ‘scientific’, not a Christian, delusion. We realise that the universe has its own rules and complications which intrude on our lives and often thwart our choices. It is therefore legitimate to talk of chance, but we often fail to appreciate the real significance of this word. Chance is not a cause; in essence it refers to our own consciousness that we are immersed in circumstance, and it has no reality without our own purposiveness. Thus chance is not some blind and indifferent or even hostile cosmic mystery; it is the occasion of our own responses, and it even offers the opportunity of human growth. Just as we accept the laws (and dangers) of physics (e.g. gravitation), as the framework of our ordered existence, so also we may accept the surprises of chance without any despairing conclusion either from our latest researches in astronomy or from a fatal accident in the street.
What is Philosophical in Philosophical Counselling?
Authors: LAHAV RAN
Published: February 2008

After a short description of the nature of philosophical counselling, this paper suggests that what makes philosophical counselling philosophical is that it helps the counsellee in philosophical self‐investigations. These are critical non‐empirical investigations of the fundamental principles underlying the counsellee's ‘lived understanding’(i.e. conceptions which the counsellee lives by, though not necessarily articulates in words), aimed at the development of wisdom.

In order to illustrate the nature of philosophical self‐investigation, two case studies are presented. The nature and measurability of success in philosophical counselling is then discussed. A questionnaire filled out by a counsellee is quoted as an illustration of the possible effects and success of philosophical counselling.
The ‘Person’in Philosophical Counselling vs. Psychotherapy and the Possibility of Interchange between the Fields
Authors: BLASS RACHEL B.
Published: February 2008

This paper suggests that a basic distinction between philosophical counselling and psychotherapy is to be found in the conception of ‘the person’that is inherent in each of the fields. Understanding this distinction allows not only for a more profound recognition of what is unique to philosophical counselling but also for a better view of possibilities of interchange between the fields. [1]
Philosophical Counselling, Truth and Self‐Interpretation
Authors: JOPLING DAVID A.
Published: February 2008

Philosophical counselling, Ran Lahav and others claim, helps clients deepen their philosophical self‐understanding. The counsellor's role is the minimalist one of providing the client with the philosophical tools needed for reflective self‐evaluation. Respect for the client's autonomy entails refraining from intervening with substantive moral criticism, theories, and methods; the client's ways of working out fundamental questions like ‘Who am I and what do I really want?’cannot be assessed by the counsellor in terms of their truth‐value, but only in terms of whether they reflect the client's autonomous choice to express him/herself in a certain way.

I argue that this view, which is informed by an anti‐realist account of self and life‐history, undermines the distinction between self‐knowledge and self‐deception. Once interpretive and criteriological free rein is given to the client, and once personal, pragmatic and aesthetic considerations take precedence over truth‐value, then the way is left open to clients to generate the most morally convenient self‐interpretation to suit their current needs.

I defend the view that truth matters in philosophical counselling; more specifically, that there is a basic distinction between true and false forms of self‐understanding. To do this, I offer a broadly realist account of self and reflective self‐evaluation. If this is right, then philosophical counsellors shoulder a significant burden of responsibility in helping their clients achieve an accurate, defensible, action‐guiding and truth‐oriented self‐understanding.
Feinberg on the Criterion of Moral Personhood
Authors: HUDSON HUD
Published: February 2008

In a very influential paper, Abortion, Joel Feinberg offers a series of arguments against four popular proposals for the criterion of moral personhood and defends a fifth proposal. In this paper, I demonstrate that two widely‐accepted arguments employed by Feinberg against the modified species criterion and the strict potentiality criterion, respectively, are unsound. Moreover, I argue that there is a general feature of his inquiry into the criteria for moral personhood which undermines his efforts to argue convincingly either in favour of his own candidate or against other candidates.
Assessment of post‐mortem‐induced changes to the mouse brain proteome
Authors: Hunsucker Stephen W. , Solomon Benjamin , Gawryluk Jeremy , Geiger Jonathan D. , Vacano Guido N. , Duncan Mark W. , Patterson David
Published: February 2008

This study was designed to assess the influence of high‐energy head‐focused microwave irradiation and the post‐mortem interval on measurements of the mouse brain proteome. Difference gel electrophoresis was used to compare mouse brain protein levels in animals killed by decapitation, where the tissue was held at 25°C for selected time intervals post‐mortem, and by high‐energy head‐focused microwave irradiation followed by immediate resection. Microwave‐mediated killing was used because it comprehensively snap‐inactivates enzymes while largely retaining brain cytoarchitecture. Of the 912 protein spots common to at least eight of 10 gels analyzed, 35 (3.8%) showed significant differences in levels (t‐test; p < 0.05) depending on whether animals were killed by microwave irradiation or decapitation. When animals were killed by decapitation, 43 protein spots (4.7%) showed changes in levels over the post‐mortem interval (anova; p < 0.05). The vast majority of the near 1000 proteins evident on a 2D gel were stable for up to 4 h. These data have important implications for studies of proteins in the brain, whether based on analysis of tissue derived from animal models or from humans.
Host‐cell specific effects of the nicotinic acetylcholine receptor chaperone RIC‐3 revealed by a comparison of human and Drosophila RIC‐3 homologues
Authors: Lansdell Stuart J. , Collins Toby , Yabe Arisa , Gee Veronica J. , Gibb Alasdair J. , Millar Neil S.
Published: February 2008

RIC‐3 is a transmembrane protein which enhances maturation (folding and assembly) of neuronal nicotinic acetylcholine receptors (nAChRs). In this study, we report the cloning and characterisation of 11 alternatively spliced isoforms of Drosophila melanogaster RIC‐3 (DmRIC‐3). Heterologous expression studies of alternatively spliced DmRIC‐3 isoforms demonstrate that nAChR chaperone activity does not require a predicted coiled‐coil domain which is located entirely within exon 7. In contrast, isoforms containing an additional exon (exon 2), which is located within a proline‐rich N‐terminal region, have a greatly reduced ability to enhance nAChR maturation. The ability of DmRIC‐3 to influence nAChR maturation was examined in co‐expression studies with human α7 nAChRs and with hybrid nAChRs containing both Drosophila and rat nAChR subunits. When expressed in a Drosophila cell line, several of the DmRIC‐3 splice variants enhanced nAChR maturation to a significantly greater extent than observed with human RIC‐3. In contrast, when expressed in a human cell line, human RIC‐3 enhanced nAChR maturation more efficiently than DmRIC‐3. The cloning and characterisation of 11 alternatively spliced DmRIC‐3 isoforms has helped to identify domains influencing RIC‐3 chaperone activity. In addition, studies conducted in different expression systems suggest that additional host cell factors may modulate the chaperone activity of RIC‐3.
A broadly neuroprotective derivative of curcumin
Authors: Liu Yuanbin , Dargusch Richard , Maher Pamela , Schubert David
Published: February 2008

The plant polyphenolic curcumin alters the response of nerve cells to some forms of toxic stress. The steroid‐like compound, cyclohexyl bisphenol A, has broad neuroprotective properties that are very distinct from those of curcumin. To incorporate both families of biological activities into a single molecule, a pyrazole derivative of curcumin, called CNB‐001, was synthesized. CNB‐001 acquires a new activity and is far superior in neuroprotection assays to either parental molecule, but retains some of the properties of both. It is neuroprotective in cell culture assays for trophic factor withdrawal, oxidative stress, excitotoxicity, and glucose starvation, as well as toxicity from both intracellular and extracellular amyloid. While the creation of CNB‐001 was based upon an uncommon approach to drug design, it has the potential of a lead drug candidate for treating multiple conditions involving nerve cell death.
Minocycline neuroprotects, reduces microglial activation, inhibits caspase 3 induction, and viral replication following Japanese encephalitis
Authors: Mishra Manoj Kumar , Basu Anirban
Published: February 2008

Minocycline is broadly protective in neurological disease models featuring inflammation and cell death and is being evaluated in clinical trials. Japanese encephalitis virus (JEV) is one of the most important causes of viral encephalitis worldwide. There is no specific treatment for Japanese encephalitis (JE) and no effective antiviral drugs have been discovered. Studies indicate that JE involves profound neuronal loss as well as secondary inflammation caused because of cell death. Minocycline is a semisynthetic second‐generation tetracycline that exerts anti‐inflammatory and antiapoptotic effects that are completely separate from its antimicrobial action. Because tetracycline treatment is clinically well tolerated, we investigated whether minocycline protects against experimental model of JE. Intravenous inoculation of GP78 strain of JEV in adult mice results in lethal encephalitis and caused primarily because of neuronal death and secondary inflammation caused because of cell death. Minocycline confers complete protection in mice following JEV infection (p < 0.0001). Neuronal apoptosis, microglial activation, active caspase activity, proinflammatory mediators, and viral titer were markedly decreased in minocycline‐treated JEV infected mice on ninth day post‐infection. Treatment with minocycline may act directly on brain cells, because neuronal cell line Neuro2a were also salvaged from JEV‐induced death. Our data suggest that minocycline may be a candidate to consider in human clinical trials for JE patients.
Regulation of psychostimulant‐induced signaling and gene expression in the striatum
Authors: McGinty Jacqueline F. , Shi Xiangdang D. , Schwendt Marek , Saylor Alicia , Toda Shigenobu
Published: February 2008

J. Neurochem. (2008) 104, 1440–1449.

Amphetamine (AMPH) and cocaine are indirect dopamine agonists that activate multiple signaling cascades in the striatum. Each cascade has a different subcellular location and duration of action that depend on the strength of the drug stimulus. In addition to activating D1 dopamine‐Gs‐coupled‐protein kinase A signaling, acute psychostimulant administration activates extracellular‐regulated kinase transiently in striatal cells; conversely, inhibition of extracellular‐regulated kinase phosphorylation decreases the ability of psychostimulants to elevate locomotor behavior and opioid peptide gene expression. Moreover, a drug challenge in rats with a drug history augments and prolongs striatal extracellular‐regulated kinase phosphorylation, possibly contributing to behavioral sensitization. In contrast, AMPH activates phosphoinositide‐3 kinase substrates, like protein kinase B/Akt, only in the nuclei of striatal cells but this transient increase induced by AMPH is followed by a delayed decrease in protein kinase B/Akt phosphorylation whether or not the rats have a drug history, suggesting that the phosphoinositide‐3 kinase pathway is not essential for AMPH‐induced behavioral sensitization. Chronic AMPH or cocaine also alters the regulation of inhibitory G protein‐coupled receptors in the striatum, as evident by a prolonged decrease in the level of regulator of G protein signaling 4 after non‐contingent or contingent (self‐administered) drug exposure. This decrease is exacerbated in behaviorally sensitized rats and reversed by re‐exposure to a cocaine‐paired environment. A decrease in regulator of G protein signaling 4 levels may weaken its interactions with metabotropic glutamate receptor 5, Gαq, and phospholipase C β that may enhance drug‐induced signaling. Alteration of these protein–protein interactions suggests that the striatum responds to psychostimulants with a complex molecular repertoire that both modulates psychomotor effects and leads to long‐term neuroadaptations.
Osmotic swelling characteristics of glial cells in the murine hippocampus, cerebellum, and retina in situ
Authors: Hirrlinger Petra G. , Wurm Antje , Hirrlinger Johannes , Bringmann Andreas , Reichenbach Andreas
Published: February 2008

Glial cells are proposed to play a major role in the ionic and osmotic homeostasis in the CNS. Swelling of glial cells contributes to the development of edema in neural tissue under pathological conditions such as trauma and ischemia. In this study, we compared the osmotic swelling characteristics of murine hippocampal astrocytes, cerebellar Bergmann glial cells, and retinal Müller glial cells in acutely isolated tissue slices in response to hypoosmotic stress and pharmacological blockade of Kir channels. Hypoosmotic challenge induced an immediate swelling of somata in the majority of Bergmann glial cells and hippocampal astrocytes investigated, whereas Müller cell bodies displayed a substantial delay in the onset of swelling and hippocampal astroglial processes remained unaffected. Blockade of Kir channels under isoosmotic conditions had no swelling‐inducing effect in Müller cell somata but caused a swelling in brain astrocytic somata and processes. Blockade of Kir channels under hypoosmotic conditions induced an immediate and strong swelling in Müller cell somata, but had no cumulative effect to brain astroglial somata. No regulatory volume decrease could be observed in all cell types. The data suggest that Kir channels are differently implicated in cell volume homeostasis of retinal Müller cells and brain astrocytes and that Müller cells and brain astrocytes differ in their osmotic swelling properties.
Structure‐activity analysis of ginkgolide binding in the glycine receptor pore
Authors: Heads Judith A. , Hawthorne Rebecca L. , Lynagh Timothy , Lynch Joseph W.
Published: February 2008

Ginkgolides, active constituents of Ginkgo biloba extracts, potently block the glycine receptor chloride channel (GlyR). Ginkgolides A, B, C and J are structurally similar, varying only by the presence or absence of oxygens at their R1 and R2 positions. The aim of this study was to understand how variable ginkgolide groups bind to pore‐lining 2′ and 6′ residues in the α1 GlyR. Ginkgolide potency was not affected by G2′A or G2′S mutations, suggesting 2′ residues are not important for ginkgolide coordination. Analysis of the α1T6′S GlyR suggests that ginkgolides bind to this receptor via hydrogen bonds between T6′S and ginkgolide R1 hydroxyls. The abolition of block by the T6′A and T6′V mutations but not by the T6′S mutation implies the existence a second transmembrane domain α‐helical kink formed by hydrogen bonding between 6′ threonine and serine sidechains and backbone carbonyl oxygens. We also found that ginkgolide A binds in different orientations in the closed and open states of a mutant GlyR, possibly reflecting its enhanced flexibility relative to other ginkgolides. Together these results indicate that small variations in ginkgolide structure or pore structure can lead to drastic potency variations. This property may be exploited to create improved pharmacological probes for discriminating among anionic Cys‐loop receptor isoforms with 6′ structural variations.
In vitro high affinity α‐synuclein binding sites for the amyloid imaging agent PIB are not matched by binding to Lewy bodies in postmortem human brain1
Authors: Ye Liang , Velasco Ana , Fraser Graham , Beach Thomas G. , Sue Lucia , Osredkar Tracy , Libri Vincenzo , Spillantini Maria Grazia , Goedert Michel , Lockhart Andrew
Published: February 2008

Amyloid containing deposits are a defining neuropathological feature of a wide range of dementias and movement disorders. The positron emission tomography tracer PIB (Pittsburgh Compound‐B, 2‐[4′‐(methylamino)phenyl]‐6‐hydroxybenzothiazole) was developed to target senile plaques, an amyloid containing pathological hallmark of Alzheimer’s disease, formed from the amyloid‐β peptide. Despite the fact that PIB was developed from the pan‐amyloid staining dye thioflavin T, no detailed characterisation of its interaction with other amyloid structures has been reported. In this study, we demonstrate the presence of a high affinity binding site (Kd∼4 nM) for benzothiazole derivatives, including [3H]‐PIB, on α‐synuclein (AS) filaments generated in vitro, and further characterise this binding site through the use of radioligand displacement assays employing 4‐N‐methylamino‐4′‐hydroxystilbene (SB13) (Ki = 87 nM) and 2‐(1‐{6‐[(2‐fluoroethyl(methyl)amino]‐2‐naphthyl}ethylidene)malononitrile (FDDNP) (Ki = 210 nM). Despite the presence of a high‐affinity binding site on AS filaments, no discernible interaction of [3H]‐PIB was detected with amygdala sections from Parkinson’s disease cases containing frequent AS‐immunoreactive Lewy bodies and related neurities. These findings suggest that the density and/or accessibility of AS binding sites in vivo are significantly less than those associated with amyloid‐β peptide lesions. Lewy bodies pathology is therefore unlikely to contribute significantly to the retention of PIB in positron emission tomography imaging studies.
The separation of antagonist from agonist effects of trisubstituted purines on CaV2.2 (N‐type) channels
Authors: Buraei Zafir , Elmslie Keith S.
Published: February 2008

Dihydropyridines can affect L‐type calcium channels (CaV1) as either agonists or antagonists. Seliciclib or R‐roscovitine, a 2,6,9‐trisubstituted purine, is a potent cyclin‐dependent kinase inhibitor that induces both agonist and antagonist effects on CaV2 channels (N‐, P/Q‐ and R‐type). We studied the effects induced by various trisubstituted purines on CaV2.2 (N‐type) channels to learn about chemical structure–function relationships. We found that S‐roscovitine and R‐roscovitine showed similar potency to inhibit, but agonist activity of S‐roscovitine required at least a 20‐fold higher concentration, suggesting stereospecificity of the agonist‐binding site. The testing of other trisubstituted purines showed a correlation between CaV2.2 inhibition and cyclin‐dependent kinase affinity that broke down after determining that a chemically unrelated inhibitor, kenpaullone, was a poor CaV2.2 inhibitor, and a kinase inactive analog (dimethylamino‐olomoucine; DMAO) was a strong inhibitor, which together support a kinase independent effect. In fact, like dihydropyridine‐induced L‐channel inhibition, R‐roscovitine left‐shifted the closed‐state inactivation versus voltage relationship, which suggests that inhibition results from CaV2 channels moving into the inactivated state. Trisubstituted purine antagonists could become clinically important drugs to treat diseases, such as heart failure and neuropathic pain that result from elevated CaV2 channel activity.
Expression of multiple AQP4 pools in the plasma membrane and their association with the dystrophin complex
Authors: Nicchia Grazia Paola , Cogotzi Laura , Rossi Andrea , Basco Davide , Brancaccio Andrea , Svelto Maria , Frigeri Antonio
Published: February 2008

Altered aquaporin‐4 (AQP4) expression has been reported in brain edema, tumors, muscular dystrophy, and neuromyelitis optica. However, the plasma membrane organization of AQP4 and its interaction with proteins such as the dystrophin‐associated protein complex are not well understood. In this study, we used sucrose density gradient ultracentrifugation and 2D blue native/sodium dodecyl sulfate–polyacrylamide gel electrophoresis and showed the expression of several AQP4 multi‐subunit complexes (pools) of different sizes, ranging from ≫ 1 MDa to ∼500 kDa and containing different ratios of the 30/32 kDa AQP4 isoforms, indicative of orthogonal arrays of particles of various sizes. A high molecular weight pool co‐purified with dystrophin and β‐dystroglycan and was drastically reduced in the skeletal muscle of mdx3cv mice, which have no dystrophin. The number and size of the AQP4 pools were the same in the kidney where dystrophin is not expressed, suggesting the presence of dystrophin‐like proteins for their expression. We found that AQP2 is expressed only in one major pool of ∼500 kDa, indicating that the presence of different pools is a peculiarity of AQP4 rather than a widespread feature in the AQP family. Finally, in skeletal muscle caveolin‐3 did not co‐purify with any AQP4 pool, indicating the absence of interaction of the two proteins and confirming that caveolae and orthogonal arrays of particles are two independent plasma membrane microdomains. These results contribute to a better understanding of AQP4 membrane organization and raise the possibility that abnormal expression of specific AQP4 pools may be found in pathological states.
Transcriptional activation of human mu‐opioid receptor gene by insulin‐like growth factor‐I in neuronal cells is modulated by the transcription factor REST
Authors: Bedini Andrea , Baiula Monica , Spampinato Santi
Published: February 2008

The human mu‐opioid receptor gene (OPRM1) promoter contains a DNA sequence binding the repressor element 1 silencing transcription factor (REST) that is implicated in transcriptional repression. We investigated whether insulin‐like growth factor I (IGF‐I), which affects various aspects of neuronal induction and maturation, regulates OPRM1 transcription in neuronal cells in the context of the potential influence of REST. A series of OPRM1‐luciferase promoter/reporter constructs were transfected into two neuronal cell models, neuroblastoma‐derived SH‐SY5Y cells and PC12 cells. In the former, endogenous levels of human mu‐opioid receptor (hMOPr) mRNA were evaluated by real‐time PCR. IGF‐I up‐regulated OPRM1 transcription in: PC12 cells lacking REST, in SH‐SY5Y cells transfected with constructs deficient in the REST DNA binding element, or when REST was down‐regulated in retinoic acid‐differentiated cells. IGF‐I activates the signal transducer and activator of transcription‐3 signaling pathway and this transcription factor, binding to the signal transducer and activator of transcription‐1/3 DNA element located in the promoter, increases OPRM1 transcription. We propose that a reduction in REST is a critical switch enabling IGF‐I to up‐regulate hMOPr. These findings help clarify how hMOPr expression is regulated in neuronal cells.
IL‐1F5 mediates anti‐inflammatory activity in the brain through induction of IL‐4 following interaction with SIGIRR/TIR8
Authors: Costelloe Ceire , Watson Melanie , Murphy Aine , McQuillan Keith , Loscher Christine , Armstrong Michelle E. , Garlanda Cecilia , Mantovani Alberto , O’Neill Luke A. J. , Mills Kingston H. G. , Lynch Marina A.
Published: February 2008

Similarity in structure and sequence homology has led to the identification of new members of the interleukin‐1 (IL‐1) ligand and receptor superfamilies. IL‐1F6, IL‐1F8 and IL‐1F9 have been shown to signal through IL‐1R‐related protein 2 and IL‐1 receptor accessory protein leading to activation of NFκB, while IL‐1F7 and IL‐1F10 interact with the IL‐18 receptor and the soluble IL‐1 receptor type I respectively. In contrast, identification of a biological role for IL‐1F5 has remained elusive, with conflicting data relating to its possible ability to antagonize IL‐1F9‐stimulated activation of NFκB in Jurkat cells transfected with IL‐1R‐related protein 2. In this study, we set out to investigate a possible role for IL‐1F5 in the brain and report that it antagonizes the inflammatory effects of IL‐1β and lipopolysaccharide (LPS) in vivo and in vitro including the inhibitory effect on long‐term potentiation (LTP) in rat hippocampus. We demonstrate that IL‐1F5 induces IL‐4 mRNA and protein expression in glia in vitro and enhances hippocampal expression of IL‐4 following intracerebroventricular (i.c.v.) injection. The inhibitory effect of IL‐1F5 on LPS‐induced IL‐1β is attenuated in cells from IL‐4‐defective (IL−4−/− mice). Our findings suggest that IL‐1F5 mediates anti‐inflammatory effects through its ability to induce IL‐4 production and that this is a consequence of its interaction with the orphan receptor, single Ig IL‐1R‐related molecule (SIGIRR)/TIR8, as the effects were not observed in SIGIRR−/− mice. In contrast to its effects in brain tissue, IL‐1F5 did not attenuate LPS‐induced changes, or up‐regulated IL‐4 in macrophages or dendritic cells, suggesting that the effect is confined to the brain.
Impacts of Market Reform on Spatial Volatility of Maize Prices in Tanzania
Authors: Kilima Fredy T. M. , Chung Chanjin , Kenkel Phil , Mbiha Emanuel R.
Published: February 2008

Maize is one of the major staples and cash crops for many Tanzanians. Excessive volatility of maize prices destabilises farm income in maize‐growing regions and is likely to jeopardise nutrition and investment in many poor rural communities. This study investigates whether market reform policies in Tanzania have increased the volatility of maize prices, and identifies regional characteristics that can be attributed to the spatial price volatility. To achieve the objectives, an autoregressive conditional heteroskedasticity in mean (ARCH‐M) model is developed and estimated in this study. Results show that the reforms have increased farm‐gate prices and overall price volatility. Maize prices are lower in surplus and less developed regions than those in deficit and developed regions. Results also show that the developed and maize‐deficit regions, and regions bordering other countries have experienced less volatile prices than less developed, maize‐surplus and non‐bordering regions. Our findings indicate that investments in communication and transportation infrastructures from government and donor countries are likely to increase inter‐regional and international trade, thereby reducing the spatial price volatility in Tanzanian maize prices in the long run.
Forecasting the Adoption of GM Oilseed Rape: Evidence from a Discrete Choice Experiment in Germany
Authors: Breustedt Gunnar , Müller‐Scheeßel Jörg , Latacz‐Lohmann Uwe
Published: February 2008

This paper explores farmers’ willingness to adopt genetically modified (GM) oilseed rape prior to its commercial release and estimates the ‘demand’ for the new technology. The analysis is based upon choice experiments with 202 German arable farmers. A multinomial probit estimation reveals that GM attributes such as gross margin, expected liability from cross pollination, or flexibility in returning to conventional oilseed rape significantly affect the likelihood of adoption. Neighbouring farmers’ attitudes towards GM cropping and a number of farmer and farm characteristics were also found to be significant determinants of prospective adoption. Demand simulations suggest that adoption rates are very sensitive to the profit difference between GM and non‐GM rape varieties. A monopolistic seed price would substantially reduce demand for the new technology. A monopolistic seed supplier would reap between 45% and 80% of the GM rent, and the deadweight loss of the monopoly would range between 15% and 30% of that rent. The remaining rent for farmers may be too small to outweigh possible producer price discounts resulting from the costs of segregating GM and non‐GM oilseed rape along the supply chain.
The Spatial Integration of Paddy Markets in Vietnam
Authors: Baulch Bob , Hansen Henrik , Trung Le Dang , Tam Tran Ngo Minh
Published: February 2008

This paper examines whether there is spatial integration between and within paddy markets in the north and south of Vietnam. The empirical model developed uses estimates of transfer costs to generalise Ravallion's model of spatial market integration to allow for threshold effects. A sequential testing strategy is used to test for market segmentation, the number of thresholds, long‐run integration, informational efficiency and the Law of One Price within an error‐correction framework. We find neither threshold effects nor weak evidence of paddy market integration between northern and southern Vietnam. There is, however, evidence of both threshold effects and stronger market integration within the Red and Mekong River deltas. Whenever price spreads exceed their thresholds, at least 60% of price changes are transmitted between regional markets within a month. Nonetheless, the instantaneous version of the Law of One Price only holds for a few regimes and market pairs. These results suggest that national level policies cannot be relied upon to stabilise or support paddy prices in Vietnam. Instead, policies need to be designed with the specific production, consumption and marketing characteristics of northern and southern Vietnam in mind.
Cost Structure and Vertical Integration between Farming and Processing
Authors: Kvaløy Ola , Tveterås Ragnar
Published: February 2008

In several food‐producing sectors, we observe vertical integration between the farming and processing stages. The salmon industry, which has motivated this paper, has seen a rise in large vertically integrated companies over the last decade, with direct ownership of production activities including hatcheries, fish processing and exporting. Both the farming and processing stages have become more capital intensive, which has led to a steeper U‐shaped average cost (AC) curve. In this paper we present a theoretical link between this technological shift and vertical integration: in a repeated game model of relational contracting, we show that when the AC curve is sufficiently steep, then processors and farmers are more likely to vertically integrate. The reason is that steep AC curves make it costly to deviate from the optimal production scale, which in turn makes processors more vulnerable to hold‐up and opportunistic behaviours from its suppliers.
Evaluating the Potential of Index Insurance Schemes to Reduce Crop Yield Risk in an Arid Region
Authors: Breustedt Gunnar , Bokusheva Raushan , Heidelbach Olaf
Published: February 2008

We evaluate yield risk reduction through weather index, area yield index and farm yield insurance contracts for wheat farms in Kazakhstan by employing data from 1980 to 2002. We use the usual mean variance (MV) approach and also a second‐degree stochastic dominance (SSD) criterion. While MV is not necessarily consistent with the expected utility (EU) theory, SSD results only in a minimum but EU‐consistent benefit from insuring. Differences in the estimation results for both approaches underline the advantage of applying both criteria to analyse the risk‐reducing potential of crop insurance. Bootstrapping results show that none of the analysed insurance schemes provides statistically significant risk reduction for every single farm. In addition, weather‐based index insurance is found to provide less risk reduction than area yield insurance based on the rayon (county) yield. Moreover, rayon yield index insurance can reduce yield risk more effectively for Kazakhstan's wheat producers than farm yield insurance with a low strike yield.
Modelling the Crop Variety Demand of Semi‐Subsistence Households: Bananas in Uganda
Authors: Edmeades Svetlana , Phaneuf Daniel J. , Smale Melinda , Renkow Mitch
Published: February 2008

We propose an approach to model the derived demand for crop varieties among semi‐subsistence farmers in a developing economy, and apply it to smallholder banana producers in Uganda. We model variety planting decisions as being composed of an extensive margin decision to grow a subset of locally available varieties (variety choice); and an intensive margin decision about the scale or extent of variety cultivation per farm (variety demand). We estimate variety demand equations using a more complete representation of the choice set upon which observed planting decisions are made. Computed elasticities of variety demand with respect to variety attributes indicate that the relative importance of consumption and production attributes varies by location and proximity to markets, from which we draw implications for the social and economic impact of crop improvement. The approach that we propose has broad appeal for analysing adoption decisions for modern or traditional varieties of both major and minor crops in developing countries.
Dental caries and body mass index by socio‐economic status in Swedish children
Authors: Gerdin Elisabeth Wärnberg , Angbratt Marianne , Aronsson Kerstin , Eriksson Elin , Johansson Ingegerd
Published: February 2008

Objectives:  The aim of the present study was to evaluate the association between dental caries, childhood body mass index (BMI), and socioeconomic status in Swedish children.

Methods:  The study cohort consisted of 2303 10‐year‐old children with data on socioeconomic status, BMI at 4, 5, 7 and 10 years of age, and caries at 6, 10 and 12 years of age. Anthropometric measures were carried out by trained nurses according to standardized routines. The occurrence of caries was registered from county records, and the children were classified into one of five socioeconomic clusters based on their census registration address.

Results:  Caries prevalence decreased with increasing socioeconomic status at all ages, whereas childhood BMI and proportion of overweight/obese children were unrelated to socioeconomic status. Obese, but not overweight, children had more caries affected teeth than non‐obese, and BMI had an independent, though weak, effect on caries variation in multiple regression. Interestingly, overweight/obese 4‐year‐olds, who had normal body weight at 5, 7 and 10 years of age, had significantly less caries than children who had normal body weight from 4 to 10 years of age.

Conclusions:  Overweight and caries prevalence are significantly associated in Swedish children. However, the association is weak. Nevertheless, the concept that child dental services and child welfare services can benefit from joint programs is supported.
The consequences of orofacial pain symptoms: a population‐based study in Hong Kong
Authors: Wong May C. M. , McMillan Anne S. , Zheng Jun , Lam Cindy L. K.
Published: February 2008

Objectives:  To investigate the impacts associated with orofacial pain symptoms among adult Chinese people in Hong Kong. Associations between impacts, pain characteristics and professional treatment seeking behaviour were explored.

Methods:  A cross‐sectional, population‐based study was conducted using a telephone survey method. A sample of Cantonese‐speaking Chinese people aged 18 years and over living in Hong Kong was interviewed. The questionnaire incorporated questions on recent orofacial pain experience and characteristics. Respondents with orofacial pain symptoms were asked about the consequences of the pain on various aspects of daily life and whether they had sought treatment for the pain.

Results:  Of the 1222 survey respondents, 41.6% reported some form of orofacial pain. 79.3% of those who reported orofacial pain and about one‐third of the total sample had experienced at least one impact. The most common impact was worried about oral and dental health (59.8%) followed by avoided certain food (50.4%). Respondents with toothache were found to be more likely to have experienced all the impacts investigated (OR range: 2.048–3.309). People who had stayed in bed more than usual (OR = 2.342), experienced sleep disturbance (OR = 2.149), and worried about their oral and dental health (OR = 2.851) were more likely to seek professional treatment.

Conclusions:  The adverse impact of orofacial pain on the well‐being of the adult population of Hong Kong was substantial. Despite this, treatment seeking was low with a high level of untreated orofacial pain symptoms.