bluuebunny/crossref_metadata_2025 huggingface dataset:
How sympatric is speciation in the Howea palms of Lord Howe Island?
Authors: BABIK WIESŁAW , BUTLIN ROGER K. , BAKER WILLIAM J. , PAPADOPULOS ALEXANDER S. T. , BOULESTEIX MATTHIEU , ANSTETT MARIE‐CHARLOTTE , LEXER CHRISTIAN , HUTTON IAN , SAVOLAINEN VINCENT
Published: August 2009

The two species of the palm genus Howea (Arecaceae) from Lord Howe Island, a minute volcanic island in the Tasman Sea, are now regarded as one of the most compelling examples of sympatric speciation, although this view is still disputed by some authors. Population genetic and ecological data are necessary to provide a more coherent and comprehensive understanding of this emerging model system. Here, we analyse data on abundance, juvenile recruitment, pollination mode and genetic variation and structure in both species. We find that Howea forsteriana is less abundant than Howea belmoreana. The genetic data based on amplified fragment length polymorphisms markers indicate similar levels of variation in the two species, despite the estimated census population size of H. belmoreana being three times larger than that of H. forsteriana. Genetic structure within species is low although some weak isolation by distance is detectable. Gene flow between species appears to be extremely limited and restricted to early‐generation hybrids – only three admixed individuals, classified as F2s or first generation backcrosses to a parental species, were found among sampled palms. We conclude that speciation in Howea was indeed sympatric, although under certain strict definitions it may be called parapatric.
Strong founder effects and low genetic diversity in introduced populations of Coqui frogs
Authors: PEACOCK MARY M. , BEARD KAREN H. , O’NEILL ERIC M. , KIRCHOFF VERONICA S. , PETERS MAUREEN B.
Published: August 2009

The success of non‐native species may depend on the genetic resources maintained through the invasion process. The Coqui (Eleutherodactylus coqui), a frog endemic to Puerto Rico, was introduced to Hawaii in the late 1980s via the horticulture trade, and has become an aggressive invader. To explore whether genetic diversity and population structure changed with the introduction, we assessed individuals from 15 populations across the Hawaiian Islands and 13 populations across Puerto Rico using six to nine polymorphic microsatellite loci and five dorsolateral colour patterns. Allelic richness (RT) and gene diversity were significantly higher in Puerto Rico than in Hawaii populations. Hawaii also had fewer colour patterns (two versus three to five per population) than Puerto Rico. We found no isolation by distance in the introduced range, even though it exists in the native range. Results suggest extensive mixing among frog populations across Hawaii, and that their spread has been facilitated by humans. Like previous research, our results suggest that Hawaiian Coquis were founded by individuals from sites around San Juan, but unlike previous research the colour pattern and molecular genetic data (nuclear and mtDNA) support two separate introductions, one on the island of Hawaii and one on Maui. Coquis are successful invaders in Hawaii despite the loss of genetic variation. Future introductions may increase genetic variation and potentially its range.
Historical vicariance and male‐mediated gene flow in the toad‐headed lizards Phrynocephalus przewalskii
Authors: URQUHART JOHN , WANG YUEZHAO , FU JINZHONG
Published: August 2009

Using mitochondrial and microsatellite DNA data and a population genetic approach, we tested male‐mediated gene flow in the toad‐headed lizards Phrynocephalus przewalskii. The mitochondrial DNA (ND2 gene), on the one hand, revealed two major lineages and a strong population genetic structure (FST = 0.692; FST′ = 0.995). The pairwise differences between the two lineages ranged from 2.1% to 6.4% and the geographical division of the two lineages coincided with a mountain chain consisting of the Helan and Yin Mountains, suggesting a historical vicariant pattern. On the other hand, the nuclear microsatellite DNA revealed a significant but small population genetic structure (FST = 0.017; FST′ = 0.372). The pairwise FST among the nine populations examined with seven microsatellite DNA loci ranged from 0.0062 to 0.0266; the assignment test failed to detect any naturally occurring population clusters. Furthermore, the populations demonstrated a weak isolation by distance and a northeast to southwest clinal variation, rather than a vicariant pattern. A historical vicariant event followed by male‐mediated gene flow appears to be the best explanation for the data. Approximately 2–5 Ma, climatic change may have created an uninhabitable zone along the Helan‐Yin mountain chain and initiated the divergence between the two mitochondrial lineages. With further climatic changes, males were able to disperse across the mountain chain, causing sufficient gene flow that eventually erased the vicariant pattern and drastically reduced the population genetic structure, while females remained philopatric and maintained the mitochondrial DNA (mtDNA) divergence. Although polygyny mating system and female philopatry may partially contribute to the reduced movement of females, other hypotheses, such as female intrasexual aggression, should also be explored.
Genetic variation in the G72 (DAOA) gene affects temporal lobe and amygdala structure in subjects affected by bipolar disorder
Authors: Zuliani Riccardo , Moorhead T William J , Job Dominic , McKirdy James , Sussmann Jessika E D , Johnstone Eve C , Lawrie Stephen M , Brambilla Paolo , Hall Jeremy , McIntosh Andrew M
Published: August 2009

Background:  Variation in the G72 (DAOA) gene is understood to convey susceptibility for bipolar disorder through an uncertain mechanism. Little is known about the structural brain phenotypes associated with this gene. We hypothesised that reductions in temporal lobe and amygdala gray matter would be associated with variation at two loci in the gene for which evidence of genetic linkage has been repeatedly demonstrated.

Methods:  We examined the temporal lobe and amygdala gray matter associations of the risk variants M23 and M24 at the 5′ end of the gene encoding G72 in 81 controls and 38 people with bipolar disorder.

Results:  Genetic variation at both the M23 and M24 loci in G72 were associated with decreased gray matter density within the left temporal pole in people with bipolar disorder. M23 was also associated with reductions in right amygdala gray matter density. The genetic imaging associations were found only in patients with bipolar disorder.

Conclusions:  Genetic variation at single nucleotide polymorphisms in the G72 gene previously associated with bipolar disorder is related to reductions in temporal pole and amygdala gray matter structure in people with bipolar disorder.
An initial report of a new biological marker for bipolar disorder: P85 evoked brain potential
Authors: Patterson Julie V , Sandman Curt A , Ring Alex , Jin Yi , Bunney Jr. William E
Published: August 2009

Objectives:  Progress toward understanding the neurobiological and genetic underpinnings of bipolar disorder has been limited by the scarcity of potential biological markers that predict its occurrence. A measure of the integrity of brain inhibitory function, sensory gating, measured using the amplitude of the evoked potential at 50 ms to the first of two paired clicks divided by the response to the second, has been characterized as a biological marker for schizophrenia. Currently, no such biological marker exists for bipolar disorder. The goal of this research was to determine how gating of an auditory brain potential at 85 ms (P85), not previously examined in sensory gating studies, differentiated control and patient groups.

Methods:  P50 and P85 auditory evoked potentials were collected from individuals diagnosed with schizoaffective disorder (n = 45), paranoid schizophrenia (n = 66), and bipolar I disorder (n = 42) using DSM‐IV criteria and the Structured Clinical Interview for DSM‐IV; and from 56 healthy controls.

Results:  The P85 gating ratio was significantly larger in the bipolar disorder group compared to each of the other groups (F3,204 = 5.47, p = 0.001, and post‐hoc tests). The P50 gating ratio was significantly larger for the schizoaffective group than for the control group (F3,204 = 2.81, p = 0.040), but did not differ from the ratio for the schizophrenia, paranoid type (p = 0.08) and bipolar groups.

Conclusions:  The previously unstudied P85 gating ratio may provide a new marker specific to bipolar disorder. The findings will promote further studies to investigate the unique contribution of this measure as an endophenotype.
Mood episodes and mood disorders: patterns of incidence and conversion in the first three decades of life
Authors: Beesdo Katja , Höfler Michael , Leibenluft Ellen , Lieb Roselind , Bauer Michael , Pfennig Andrea
Published: August 2009

Objectives:  Significant questions remain regarding both the incidence patterns of mood episodes in adolescents and young adults from the community and the conversion rate from unipolar to bipolar disorders. We addressed these issues by examining data from a prospective longitudinal community study to (i) determine the cumulative incidence of mood episodes and disorders in the first three decades of life; (ii) determine the risk for first onset of depression among individuals with a previous history of hypomanic/manic episodes and vice versa; and (iii) determine the clinical and treatment characteristics of these subjects.

Methods:  Using the Munich‐Composite International Diagnostic Interview, clinically trained interviewers assessed mood episodes and mental disorders in 3,021 community subjects (aged 14–24 at baseline and 21–34 at third follow‐up).

Results:  The estimated cumulative incidence at age 33 was 2.9% for manic, 4.0% for hypomanic, 29.4% for major depressive, and 19.0% for minor depressive episodes; overall, 26.0% had unipolar major depression, 4.0% bipolar depression, 1.5% unipolar mania, and 3.6% unipolar hypomania (no major depression). Overall, 0.6% and 1.8% had unipolar mania or hypomania, respectively, without indication for even minor depression. A total of 3.6% of the initial unipolar major depression cases subsequently developed (hypo)mania, with particularly high rates in adolescent onset depression (< 17 years: 9%). A total of 49.6% of the initial unipolar mania cases subsequently developed major depression and 75.6% major or minor depression. While bipolar cases had more adverse clinical and course depression characteristics and higher treatment rates than unipolar depressed cases, bipolar cases did not significantly differ in mania characteristics from unipolar mania cases.

Conclusions:  Unipolar and bipolar mood disorders are more frequent than previously thought in adolescence and young adulthood, a time period when both the recognition and the intervention rates by the healthcare system are rather low. ‘Conversion’ to bipolar disorder is limited in initial unipolar depression, but common in initial unipolar mania. The remaining unipolar mania cases appear to be significant in terms of clinical and course characteristics and thus require more research attention to replicate these findings.
Behaviorally evoked transient reorganization of hippocampal spines
Authors: Kitanishi Takuma , Ikegaya Yuji , Matsuki Norio
Published: August 2009

Dendritic spines, microstructures that receive the majority of excitatory synaptic inputs, are fundamental units to integrate and store neuronal information. The morphological reorganization of spines accompanies the functional alterations in synaptic strength underlying memory‐relevant modifications of network connectivity. Here we report the rapid dynamics of cell population‐selective spine reorganizations related to behavioral experiences. In Thy1‐GFP transgenic mice, hippocampal CA1 pyramidal neurons that were putatively activated during environmental explorations were detected with their post hoc immunoreactivity for Arc, an activity‐dependent immediately‐early gene. Immediately after a 60‐min exposure to a familiar environment, the spine densities of Arc‐positive and Arc‐negative neurons were differently distributed. This density imbalance was due exclusively to changes in the number of small, rather than large, spines. The change disappeared within 60 min after mice were returned to the home cages. Thus, spines possess the ability to rapidly and reversibly alter their morphology in response to a brief environmental change. We propose that these transient spine dynamics represent a latent preliminary stage for longer‐term plasticity on demand.
The fusiform face area and occipital face area show sensitivity to spatial relations in faces
Authors: Rhodes Gillian , Michie Patricia T. , Hughes Matthew E. , Byatt Graham
Published: August 2009

Behavioral research indicates that successful face individuation is associated with sensitivity to subtle spatial relations between facial features, as well as to the features themselves. We used a blocked functional magnetic resonance adaptation paradigm to examine the sensitivity of the core face network to spatial relations in faces. The fusiform face area (FFA) was sensitive to spatial relations, responding more strongly to a single face presented with various feature spacings than to repeated presentations of an identical face. This response to spacing variations was as strong as the response to a series of distinct identities. There were no hemisphere effects in sensitivity to spatial relations, although FFAs were larger on the right. The right occipital face area (OFA) was also sensitive to spatial relations in faces. Few participants showed left OFAs. The superior temporal sulcus (STS), which does not code identity, showed little sensitivity to either relational changes or changes in identity. We suggest that the sensitivity of the FFA and right OFA to spatial relations in faces may contribute to our impressive ability to individuate faces despite their similarity as visual patterns.
Development of epileptiform excitability in the deep entorhinal cortex after status epilepticus
Authors: Bragin Denis E. , Sanderson Jennifer L. , Peterson Steven , Connor John A. , Müller Wolfgang S.
Published: August 2009

Epileptiform neuronal activity during seizures is observed in many brain areas, but its origins following status epilepticus (SE) are unclear. We have used the Li low‐dose pilocarpine rat model of temporal lobe epilepsy to examine early development of epileptiform activity in the deep entorhinal cortex (EC). We show that during the 3‐week latent period that follows SE, an increasing percentage of neurons in EC layer 5 respond to a single synaptic stimulus with polysynaptic burst depolarizations. This change is paralleled by a progressive depolarizing shift of the inhibitory postsynaptic potential reversal potential in layer 5 neurons, apparently caused by upregulation of the Cl− inward transporter NKCC1 and concurrent downregulation of the Cl− outward transporter KCC2, both changes favoring intracellular Cl− accumulation. Inhibiting Cl− uptake in the latent period restored more negative GABAergic reversal potentials and eliminated polysynaptic bursts. The changes in the Cl− transporters were highly specific to the deep EC. They did not occur in layers 1–3, perirhinal cortex, subiculum or dentate gyrus during this period. We propose that the changes in Cl− homeostasis facilitate hyperexcitability in the deep entorhinal cortex leading to epileptiform discharge there, which subsequently affects downstream cortical regions.
Reconstruction of the nigrostriatal dopamine pathway in the adult mouse brain
Authors: Thompson Lachlan H. , Grealish Shane , Kirik Deniz , Björklund Anders
Published: August 2009

Transplants of fetal dopamine neurons can be used to restore dopamine neurotransmission in animal models of Parkinson’s disease, as well as in patients with advanced Parkinson’s disease. In these studies the cells are placed in the striatum rather than in the substantia nigra where they normally reside, which may limit their ability to achieve full restoration of motor function. Using a microtransplantation approach, which allows precise placement of small cell deposits directly into the host substantia nigra, and fetal donor cells that express green fluorescent protein under the control of the tyrosine hydroxylase promoter, we show that dopamine neuroblasts implanted into the substantia nigra of adult mice are capable of generating a new nigrostriatal pathway with an outgrowth pattern that matches the anatomy of the intrinsic system. This target‐directed regrowth was closely aligned with the intrinsic striatonigral fibre projection and further enhanced by over‐expression of glial cell line‐derived neurotrophic factor in the striatal target. Results from testing of amphetamine‐induced rotational behaviour suggest, moreover, that dopamine neurons implanted into the substantia nigra are also capable of integrating into the host circuitry at the functional level.
PHENOMENOLOGY AND INTERPRETATION BEYOND THE FLESH
Authors: BOETZKES AMANDA
Published: August 2009

This article explores the ethical questions surrounding the phenomenological approach to interpretation in art history. It addresses contemporary art, from postminimalist sculpture to installation. Although the risk of phenomenology is that it merely confirms and reproduces the viewer's perceptual expectations, in fact, on a deeper level, the notion of the ontological intertwining of the viewer and the artwork demands a receptive stance in the face of art. Through an investigation of the notions of embodiment, intentionality, and mode of confrontation, I suggest that phenomenology not only mediates a trenchant understanding of the perceptual experience of the artwork, it is predicated on an acknowledgement of the artwork's alterity from interpretation. In this way, it invites a consideration of the linguistic malleability implicit in the fleshly chiasm that binds the viewer to the artwork.
SURVEYING CONTEMPORARY ART: POST‐WAR, POSTMODERN, AND THEN WHAT?
Authors: KARLHOLM DAN
Published: August 2009

This article looks at influential survey texts on world art history since c. 1980, and considers how they have dealt with the art nearest to them in time. I examine the terminology used, and problems of classification, periodization, and history writing at large. In order to describe how these texts struggle with the terms contemporary and postmodern, I focus on their treatment of conceptual art and two artists: Joseph Beuys and Cindy Sherman. The symbolic and economic consolidation of contemporary art during the last decade or so prompts me to establish a broader frame of understanding, linking it to constructions of the contemporary in the nineteenth century and to the idea of co‐existing temporalities for art.
MICHEL FOUCAULT AND THE POINT OF PAINTING
Authors: SOUSSLOFF CATHERINE M.
Published: August 2009

This article offers a historiographical analysis of Foucault's contribution to art theory by arguing that the philosopher used the medium of painting and its history since Alberti to explore the differences in the concept of realism between 1650 and his own day. I argue that in his four essays on painting written between 1966 and 1976 Foucault took up the relation of painting to knowledge (savoir), particularly the question of how painting means using an innovative approach that he termed historical. Like the phenomenologists who immediately preceded him, Foucault understood painting as related to our understanding of how knowledge is communicated or felt rather than of how it exists as philosophy. This article explores the consequences of Foucault's contribution to the history of painting for both art history and visual studies.
KARL MANNHEIM AND ALOIS RIEGL: FROM ART HISTORY TO THE SOCIOLOGY OF CULTURE
Authors: TANNER JEREMY
Published: August 2009

Karl Mannheim and Erwin Panofsky took Alois Riegl's concept of Kunstwollen as their point of departure in the development of the sciences of cultural interpretation. This article seeks to elucidate the very different readings of Riegl made by Mannheim and Panofsky, and to show how the sociological appropriation and transformation of the concept of Kunstwollen was central to the development of Mannheim's sociology of knowledge, and in particular to the analysis of ‘styles of thought’ in his classic study Conservative Thought (1927). The limited reception of Mannheim's synthesis of sociology and art history is interpreted in the intellectual context of Britain immediately after the 1939–45 war.
CONSUETUDO CARNALIS IN AUGUSTINE'S CONFESSIONS: Confessing Identity/Belonging to Difference
Authors: Skerrett Kathleen Roberts
Published: August 2009

The political theorist William E. Connolly reads Augustine's Confessions as an exhortation to deny the paradox of identity/difference. The paradox for Connolly is this: if one confesses a true identity, one must be false to difference, but if one is true to difference, one must sacrifice the promise of true identity. I revisit Augustine's Confessions here in order to offer a reading of their paradoxical character that contrasts with Connolly's. I will argue that Augustine's confession does not deny the paradox of identity/difference but exemplifies what it means to struggle within it. I turn to James Wetzel's work on Augustine's idea of free will and Catherine Keller's work on the doctrine of creatio ex nihilo to suggest that treating Augustine's confession as confession reveals this struggle.
Why Seek Asylum? The Roles of Integration and Financial Support
Authors: Zimmermann Susan
Published: August 2009

The suspicion that asylum seekers seek beneficial conditions in host areas has become a controversial and popular topic. It has led to accusations of economic migration, with deterrent and preventative measures introduced to try to control this “problem”, and in particular, the intended uniformity of asylum procedures has been a key aim of European harmonisation talks. As a small, qualitative study, this article is based upon thirteen semi‐structured interviews held with Somali individuals who sought asylum. It aims to explore destination choices with reference to the experiences and explanations given by some whose voices are otherwise largely excluded from debates. It asks to what extents and why they occurred. It reveals that having homes, jobs, educations, and more were key parts of what exile meant to these individuals, and so demonstrates reactivity behind topics more typically held to be “voluntary” concerns. Choices upon destinations were limited, however, and far bigger influences were the people smugglers or agents whom most relied upon to facilitate their entries past the preventative border controls. Beyond this, deterrence or prevention measures had no effect. The data is also used to explore the controversial and similarly under‐researched role of financial support. It is shown to have been connected with the interests that persons had in adjusting to new areas and dealing with their interim disadvantage, and not as something that justifies suspicions. This study supports arguments that policy makers should concentrate less upon deterrence or prevention, and more on the conditions that exist to propel such movements. Its findings suggest that insufficient certainty, support, or quality of life can create pressures for seeking asylum and that these should be addressed by policy makers; it also argues that “voluntary” aspects of movements might more recognisably be parts of exile.
A new trigemino-nociceptive stimulation model for event-related fMRI
Authors: Stankewitz A , Voit HL , Bingel U , Peschke C , May A
Published: August 2009

Functional imaging of human trigemino-nociceptive processing provides meaningful insights into altered pain processing in head and face pain diseases. Although functional magnetic resonance imaging (fMRI) offers high temporal and spatial resolution, most studies available were done with radioligand-positron emission tomography, as fMRI requires non-magnetic stimulus equipment and fast on–off conditions. We developed a new approach for painful stimulation of the trigeminal nerve that can be implemented within an event-related design using fMRI and aimed to detect increased blood-oxygen-level-dependent (BOLD) signals as surrogate markers of trigeminal pain processing. Using an olfactometer, 20 healthy volunteers received intranasally standardized trigeminal nociceptive stimuli (ammonia gas) as well as olfactory (rose odour) and odourless control stimuli (air puffs). Imaging revealed robust BOLD responses to the trigeminal nociceptive stimulation in cortical and subcortical brain areas known to be involved in pain processing. Focusing on the trigeminal pain pathway, significant activations were observed bilaterally in brainstem areas at the trigeminal nerve entry zone, which are agreeable with the principal trigeminal nuclei. Furthermore, increased signal changes could be detected ipsilaterally at anatomical localization of the trigeminal ganglion and bilaterally in the rostral medulla, which probably represents the spinal trigeminal nuclei. However, brainstem areas involved in the endogenous pain control system that are close to this anatomical localization, such as raphe nuclei, have to be discussed. Our findings suggest that mapping trigeminal pain processing using fMRI with this non-invasive experimental design is feasible and capable of evoking specific activations in the trigeminal nociceptive system. This method will provide an ideal opportunity to study the trigeminal pain system in both health and pathological conditions such as idiopathic headache disorders.
Methylprednisolone therapy for short-term prevention of SUNCT syndrome
Authors: Trauninger A , Alkonyi B , Kovács N , Komoly S , Pfund Z
Published: August 2009

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is characterized by severe and frequent daily pain attacks causing transient physical disability for the patients during the headache period. Currently there is no option for abortive treatment of the attacks, mainly due to the short-lived nature and frequency of the repeated headaches, while highly efficacious therapy is also unavailable for short-term prevention. We report rapidly suppressed headache attacks with orally administered methylprednisolone in eight headache periods of three patients with idiopathic, episodic SUNCT syndrome. The remission was maintained until the period was over in all cases. Although the mechanism of methylprednisolone action is unclear, it is probably based on the anti-inflammatory effects of the drug.
Incidence and predictors of chronic headache attributed to whiplash injury
Authors: Obermann M , Nebel K , Riegel A , Thiemann D , Yoon M-S , Keidel M , Stude P , Diener HC , Katsarava Z
Published: August 2009

We identified clinical, demographic and psychological predictive factors that may contribute to the development of chronic headache associated with mild to moderate whiplash injury [Quebec Task Force (QTF) ≤ II] and determined the incidence of this chronic pain state. Patients were recruited prospectively from six participating accident and emergency departments. While 4.6% of patients developed chronic headache attributed to whiplash injury according to the International Classification of Headache Disorders, 2nd edn criteria, 15.2% of patients complained about headache lasting > 42 days (QTF criteria). Predictive factors were pre-existing facial pain [odds ratio (OR) 9.7, 95% confidence interval (CI) 2.1, 10.4; P = 0.017], lack of confidence to recover completely (OR 5.5, 95% CI 2.0, 13.2; P = 0.005), sore throat (OR 5.0, 95% CI 1.5, 8.9; P = 0.013), medication overuse (OR 4.2, 95% CI 1.4, 12.3; P = 0.009), high Neck Disability Index (OR 4.0, 95% CI 1.3, 12.6; P = 0.019), hopelessness/anxiety (OR 3.8, 95% CI 1.3, 8.7; P = 0.024), and depression (OR 3.3, 95% CI 1.2, 9.4; P = 0.024). The lack of a control group limits the conclusions that can be drawn from this study. Identified predictors closely resemble those found in chronic primary headache disorders.
Clinical and neuroimaging evidence of interictal cerebellar dysfunction in FHM2
Authors: Grimaldi D , Tonon C , Cevoli S , Pierangeli G , Malucelli E , Rizzo G , Soriani S , Montagna P , Barbiroli B , Lodi R , Cortelli P
Published: August 2009

We used multimodal magnetic resonance (MR) techniques [brain diffusion-weighted magnetic resonance imaging, diffusion-weighted imaging (DWI), proton MR spectroscopy (MRS), 1H-MRS; and skeletal muscle phosphorous MRS, 31P-MRS] to investigate interictal brain microstructural changes and tissue energy metabolism in four women with genetically determined familial hemiplegic migraine type 2 (FHM2), belonging to two unrelated families, compared with 10 healthy women. Brain DWI revealed a significant increase of the apparent diffusion coefficient median values in the vermis and cerebellar hemispheres of FHM2 patients, preceding in two subjects the onset of interictal cerebellar deficits. 31P-MRS revealed defective energy metabolism in skeletal muscle of FHM2 patients, while brain 1H-MRS showed a mild pathological increase in lactate in the lateral ventricles of one patient and a mild reduction of cortical N-acetyl-aspartate to creatine ratio in another one. Our MRS results showed that a multisystem energy metabolism defect in FHM2 is associated with microstructural cerebellar changes detected by DWI, even before the onset of cerebellar symptoms.
Endemicity and palaeobiogeography of the Osteostraci and Galeaspida: a test of scenarios of gnathostome evolution
Authors: SANSOM ROBERT S.
Published: August 2009

Abstract: Armoured stem‐gnathostomes (jawless vertebrates previously termed ‘ostracoderms’) have long been assumed to exhibit strong endemicity. This assumption has underpinned their utility in many palaeobiogeographic studies as well as scenarios regarding the evolution and dominance of jawed vertebrates over their jawless relatives. The hypothesis of endemicity in stem‐gnathostomes is investigated for the first time in the light of the phylogeny of the closest relatives of jawed vertebrates – Osteostraci and Galeaspida. Palaeobiogeography of each is reconstructed using Fitch optimization and modified Brooks Parsimony Analysis. Palaeobiogeographic distributions corroborate phylogeny. Results, along with consideration of the Heterostraci, enable identification of similar patterns across groups (broad ancestral range, Early Devonian expansion, endemic and pandemic clades within each, and Middle Devonian radiation events) and inferences to the palaeogeographic relationship between major terranes (i.e. Laurentia, Baltica, Avalonia, Kara, Altaids, South China, Tarim). Comparison of basin and terrane level analyses identifies the different palaeogeographic processes responsible for the distributions of each group: sea‐level changes in the case of the Osteostraci and rifting in the case of the Galeaspida. The general endemic nature of the Osteostraci and Galeaspida is confirmed, and thus the hypothesis that the demise and extinction of stem‐gnathostomes was because of their limited dispersal capacity is supported.
Pharmacological and electrophysiological characterization of nine, single nucleotide polymorphisms of the hERG‐encoded potassium channel
Authors: Männikkö R , Overend G , Perrey C , Gavaghan CL , Valentin J‐P , Morten J , Armstrong M , Pollard CE
Published: August 2009

Background and purpose:  Potencies of compounds blocking KV11.1 [human ether‐ago‐go‐related gene (hERG)] are commonly assessed using cell lines expressing the Caucasian wild‐type (WT) variant. Here we tested whether such potencies would be different for hERG single nucleotide polymorphisms (SNPs).

Experimental approach:  SNPs (R176W, R181Q, Del187‐189, P347S, K897T, A915V, P917L, R1047L, A1116V) and a binding‐site mutant (Y652A) were expressed in Tet‐On CHO‐K1 cells. Potencies [mean IC50; lower/upper 95% confidence limit (CL)] of 48 hERG blockers was estimated by automated electrophysiology [IonWorks™ HT (IW)]. In phase one, rapid potency comparison of each WT‐SNP combination was made for each compound. In phase two, any compound‐SNP combinations from phase one where the WT upper/lower CL did not overlap with those of the SNPs were re‐examined. Electrophysiological WT and SNP parameters were determined using conventional electrophysiology.

Key results:  IW detected the expected sixfold potency decrease for propafenone in Y652A. In phase one, the WT lower/upper CL did not overlap with those of the SNPs for 77 compound‐SNP combinations. In phase two, 62/77 cases no longer yielded IC50 values with non‐overlapping CLs. For seven of the remaining 15 cases, there were non‐overlapping CLs but in the opposite direction. For the eight compound‐SNP combinations with non‐overlapping CLs in the same direction as for phase 1, potencies were never more than twofold apart. The only statistically significant electrophysiological difference was the voltage dependence of activation of R1047L.

Conclusion and implications:  Potencies of hERG channel blockers defined using the Caucasian WT sequence, in this in vitro assay, were representative of potencies for common SNPs.

This article is part of a themed section on QT safety. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2010
Armington Elasticities and Tariff Regime: An Application to European Union Rice Imports
Authors: Huchet‐Bourdon Marilyne , Pishbahar Esmaeil
Published: August 2009

The European Union’s (EU) import sources for rice include developing countries and least developed countries (LDCs). The EU has made a commitment to allow duty‐free and quota‐free access to rice imports originating in the LDCs from September 2009 onward. The purpose of this article is to answer two questions: (1) does the inclusion of import tariffs lead to different estimated Armington elasticities? (2) when a discriminating tariff is introduced, what happens to the market share of large rice exporters to the EU, especially of poor countries? We present the Armington model, derived from a constant elasticity of substitution (CES) utility function, and a non‐homothetic CES utility functional form, which is more flexible. We then estimate the Armington model, with and without the inclusion of a tariff, and we compare the elasticities. Lastly, we model five scenarios with different discriminated import tariff rates to calculate the changes in the market access of large rice exporters to the EU. Our empirical results show the importance of non‐homothetic preferences and import tariffs. Ignoring import tariffs and the non‐homothetic parameter may produce results which are biased and of uncertain validity. Furthermore, the simulation findings demonstrate that, in spite of a large difference between import tariff rate of Suriname and other countries (scenario V), its market access would not change greatly. This may be caused by supply side problems like poor infrastructures, weak technology and small capacity production in LDCs.
Consumer Acceptance of Second‐Generation GM Foods: The Case of Biofortified Cassava in the North‐east of Brazil
Authors: González Carolina , Johnson Nancy , Qaim Matin
Published: August 2009

Biofortified staple foods are currently being developed to reduce problems of micronutrient malnutrition among the poor. This partly involves use of genetic modification. Yet, relatively little is known about consumer acceptance of such second‐generation genetically modified (GM) foods in developing countries. Here, we analyse consumer attitudes towards provitamin A GM cassava in the north‐east of Brazil. Based on stated preference data, mean willingness to pay is estimated at 60–70% above market prices for traditional cassava. This is higher than the results from similar studies in developed countries, which is plausible given that micronutrient malnutrition is more severe in developing countries. GM foods with enhanced nutritive attributes seem to be well received by poor consumers. However, the results also suggest that acceptance would be still higher if provitamin A were introduced to cassava through conventional breeding. Some policy implications are discussed.
A Functional Polymorphism of the NFKB1 Gene Increases the Risk for Alcoholic Liver Cirrhosis in Patients With Alcohol Dependence
Authors: Marcos Miguel , Pastor Isabel , González‐Sarmiento Rogelio , Laso Francisco Javier
Published: August 2009

Background:  The genetic basis for the predisposition to alcoholic liver cirrhosis (ALC) remains unknown. Increasing evidence supports a role for the nuclear factor (NF)‐κB, the NF‐κB inhibitor α (NFKBIA), and the peroxisome proliferator‐activated receptor (PPAR)‐γ in the pathogenesis of alcoholic liver disease, raising the possibility that common polymorphisms in genes encoding these molecules may confer susceptibility to ALC. The objective of this study was to analyze the relationship between common polymorphisms in NFKB1, NFKBIA, and PPARG2 genes and the presence of ALC.

Methods:  A total of 258 male alcoholics (161 without liver disease and 97 with ALC) and 101 healthy controls were genotyped for the −94ins/delATTG NFKB1, 3′‐UTR+126G>A NFKBIA, and 34C>G PPARG2 polymorphisms. The association of these genetic variants with ALC was tested in alcoholic patients with alcohol abuse and alcohol dependence. A logistic regression analysis was further performed to analyze the model of inheritance.

Results:  We found an association between the presence of the deletion allele in NFKB1 polymorphism and ALC in patients with alcohol dependence. We found no association between NFKBIA and PPARG2 polymorphisms and the presence of ALC.

Conclusions:  The deletion allele of the −94ins/del NFKB1 polymorphism could be associated with a higher risk of developing ALC through an increase in inflammation, as supported by previous data.
A Randomized, Double‐Blind, Placebo‐Controlled Pilot Study of Naltrexone in Outpatients With Bipolar Disorder and Alcohol Dependence
Authors: Brown E. Sherwood , Carmody Thomas J. , Schmitz Joy M. , Caetano Raul , Adinoff Bryon , Swann Alan C. , Rush A. John
Published: August 2009

Background:  Alcohol dependence is extremely common in patients with bipolar disorder and is associated with unfavorable outcomes including treatment nonadherence, violence, increased hospitalization, and decreased quality of life. While naltrexone is a standard treatment for alcohol dependence, no controlled trials have examined its use in patients with co‐morbid bipolar disorder and alcohol dependence. In this pilot study, the efficacy of naltrexone in reducing alcohol use and on mood symptoms was assessed in bipolar disorder and alcohol dependence.

Methods:  Fifty adult outpatients with bipolar I or II disorders and current alcohol dependence with active alcohol use were randomized to 12 weeks of naltrexone (50 mg/d) add‐on therapy or placebo. Both groups received manual‐driven cognitive behavioral therapy designed for patients with bipolar disorder and substance‐use disorders. Drinking days and heavy drinking days, alcohol craving, liver enzymes, and manic and depressed mood symptoms were assessed.

Results:  The 2 groups were similar in baseline and demographic characteristics. Naltrexone showed trends (p < 0.10) toward a greater decrease in drinking days (binary outcome), alcohol craving, and some liver enzyme levels than placebo. Side effects were similar in the 2 groups. Response to naltrexone was significantly related to medication adherence.

Conclusions:  Results suggest the potential value and acceptable tolerability of naltrexone for alcohol dependence in bipolar disorder patients. A larger trial is needed to establish efficacy.
Binge Drinking Affects Attentional and Visual Working Memory Processing in Young University Students
Authors: Crego Alberto , Holguín Socorro Rodriguez , Parada María , Mota Nayara , Corral Montserrat , Cadaveira Fernando
Published: August 2009

Background:  Binge Drinking (BD) typically involves heavy drinking over a short time, followed by a period of abstinence, and is common among young people, especially university students. Animal studies have demonstrated that this type of alcohol consumption causes brain damage, especially in the nonmature brain. The aim of the present study was to determine how BD affects brain functioning in male and female university students, during the performance of a visual working memory task.

Methods:  Event‐related potentials (ERPs) were recorded, with an extensive set of 32 scalp electrodes, in 95 first‐year university students (age range 18 to 20 years), comprising 42 binge drinkers (BD) and 53 controls, in a visual “identical pairs” continuous performance task. Principal components analysis was used to identify and analyze the N2 (negative waveform with a latency around 200 to 300 ms related to attentional processes) and P3 (positive waveform with a latency around 300 to 600 ms related to working memory processes) components of the ERPs.

Results:  In the matching condition of the task, the N2 component in central and parietal regions was significantly larger in the BD than in the control group. In the control group, the P3 component was larger in the matching than in the nonmatching condition in the frontal, central, and parietal regions, whereas the BD group did not show any significant differences between conditions in any region.

Conclusions:  The results of this study confirm the presence of electrophysiological differences between young university student binge drinkers and controls during the execution of a visual task with a high working memory load. The larger N2 in the BD group suggests higher levels of attentional effort required by this group to perform the task adequately. The absence of any differences in the P3 component in the different conditions (matching and nonmatching stimuli) in the BD group suggests a deficiency in the electrophysiological differentiation between relevant and irrelevant information, which may reflect some impairment of working memory processes.
Alcoholism and Dampened Temporal Limbic Activation to Emotional Faces
Authors: Marinkovic Ksenija , Oscar‐Berman Marlene , Urban Trinity , O’Reilly Cara E. , Howard Julie A. , Sawyer Kayle , Harris Gordon J.
Published: August 2009

Background: Excessive chronic drinking is accompanied by a broad spectrum of emotional changes ranging from apathy and emotional flatness to deficits in comprehending emotional information, but their neural bases are poorly understood.

Methods: Emotional abnormalities associated with alcoholism were examined with functional magnetic resonance imaging in abstinent long‐term alcoholic men in comparison to healthy demographically matched controls. Participants were presented with emotionally valenced words and photographs of faces during deep (semantic) and shallow (perceptual) encoding tasks followed by recognition.

Results: Overall, faces evoked stronger activation than words, with the expected material‐specific laterality (left hemisphere for words, and right for faces) and depth of processing effects. However, whereas control participants showed stronger activation in the amygdala and hippocampus when viewing faces with emotional (relative to neutral) expressions, the alcoholics responded in an undifferentiated manner to all facial expressions. In the alcoholic participants, amygdala activity was inversely correlated with an increase in lateral prefrontal activity as a function of their behavioral deficits. Prefrontal modulation of emotional function as a compensation for the blunted amygdala activity during a socially relevant face appraisal task is in agreement with a distributed network engagement during emotional face processing.

Conclusions: Deficient activation of amygdala and hippocampus may underlie impaired processing of emotional faces associated with long‐term alcoholism and may be a part of the wide array of behavioral problems including disinhibition, concurring with previously documented interpersonal difficulties in this population. Furthermore, the results suggest that alcoholics may rely on prefrontal rather than temporal limbic areas in order to compensate for reduced limbic responsivity and to maintain behavioral adequacy when faced with emotionally or socially challenging situations.
Ethanol Inhibits Muscarinic Receptor‐Induced Axonal Growth in Rat Hippocampal Neurons
Authors: VanDeMark Kathryn L. , Guizzetti Marina , Giordano Gennaro , Costa Lucio G.
Published: August 2009

Background: In utero alcohol exposure can lead to fetal alcohol spectrum (FAS) disorders characterized by cognitive and behavioral deficits. In vivo and in vitro studies have shown that ethanol alters neuronal development. One mechanism through which ethanol has been shown to exert its effects is the perturbation of activated signaling cascades. The cholinergic agonist carbachol has been shown to induce axonal outgrowth through intracellular calcium mobilization, protein kinase C (PKC) activation, and ERK1/2 phosphorylation. This study investigated the effect of ethanol on the differentiation of rat hippocampal pyramidal neurons induced by carbachol as a possible mechanism involved in the developmental neurotoxicity of ethanol.

Methods: Prenatal rat hippocampal pyramidal neurons were treated with ethanol (50 to 75 mM) in the presence or absence of carbachol for 24 hours. Neurite outgrowth was assessed spectrophotometrically; axonal length was measured in neurons fixed and immunolabeled with the neuron‐specific βIII tubulin antibody; cytotoxicity was analyzed using the thiazolyl blue tetrazolium bromide assay. The effect of ethanol on carbachol‐stimulated intracellular calcium mobilization was assessed utilizing the fluorescent calcium probe, Fluo‐3AM. The PepTag® assay for nonradioactive detection of PKC from Promega was used to measure PKC activity, and ERK1/2 activation was determined by densitometric analysis of Western blots probed for phospo‐ERK1/2.

Results: Ethanol treatment (50 to 75 mM) caused an inhibition of carbachol‐induced axonal growth, without affecting neuronal viability. Neuron treatment for 15 minutes with ethanol did not inhibit the carbachol‐stimulated rise in intracellular calcium, while inhibiting PKC activity at the highest tested concentration and ERK1/2 phosphorylation at both the concentrations used in this study. On the other hand, neuron treatment for 24 hours with ethanol significantly inhibited carbachol‐induced increase in intracellular calcium.

Conclusions: Ethanol inhibited carbachol‐induced neurite outgrowth by inhibiting PKC and ERK1/2 activation. These effects may be, in part, responsible for some of the cognitive deficits associated with in utero alcohol exposure.
Inflation Differentials between Spain and the EMU: A DSGE Perspective
Authors: RABANAL PAU
Published: August 2009

This paper estimates a dynamic stochastic general equilibrium model of a currency union with nominal rigidities to explain the sources of inflation differentials between the Economic Monetary Union (EMU) and one of its member countries, Spain. The paper finds that productivity shocks account for 85% of the variability of the inflation differential. Demand shocks explain a large fraction of output growth volatility but not variability in inflation differentials. In addition, the estimated model finds evidence that inflation dynamics are different across countries in the nontradable sector only. Finally, the Balassa–Samuelson effect does not appear to be an important driver of the inflation differential during the EMU period.
The Composition of Government Spending and the Real Exchange Rate
Authors: GALSTYAN VAHAGN , LANE PHILIP R.
Published: August 2009

We show that the composition of government spending influences the long‐run behavior of the real exchange rate. We develop a two‐sector small open‐economy model in which an increase in government consumption is associated with real appreciation, while an increase in government investment may generate real depreciation. Our empirical work confirms that government consumption and government investment have differential effects on the real exchange rate and the relative price of nontradables.