bluuebunny/crossref_metadata_2025 huggingface dataset:
A lock-and-key model for protein–protein interactions
Authors: Morrison Julie L. , Breitling Rainer , Higham Desmond J. , Gilbert David R.
Published: June 2006

Motivation: Protein–protein interaction networks are one of the major post-genomic data sources available to molecular biologists. They provide a comprehensive view of the global interaction structure of an organism's proteome, as well as detailed information on specific interactions. Here we suggest a physical model of protein interactions that can be used to extract additional information at an intermediate level: It enables us to identify proteins which share biological interaction motifs, and also to identify potentially missing or spurious interactions.

Results: Our new graph model explains observed interactions between proteins by an underlying interaction of complementary binding domains (lock-and-key model). This leads to a novel graph-theoretical algorithm to identify bipartite subgraphs within protein–protein interaction networks where the underlying data are taken from yeast two-hybrid experimental results. By testing on synthetic data, we demonstrate that under certain modelling assumptions, the algorithm will return correct domain information about each protein in the network. Tests on data from various model organisms show that the local and global patterns predicted by the model are indeed found in experimental data. Using functional and protein structure annotations, we show that bipartite subnetworks can be identified that correspond to biologically relevant interaction motifs. Some of these are novel and we discuss an example involving SH3 domains from the Saccharomyces cerevisiae interactome.

Availability: The algorithm (in Matlab format) is available (see )

Contact: jmorriso@dcs.gla.ac.uk

Supplementary information: Supplementary data are available at .
American Ginseng Stimulates Insulin Production and Prevents Apoptosis through Regulation of Uncoupling Protein‐2 in Cultured β Cells
Authors: Luo John Zeqi , Luo Luguang
Published: June 2006

American ginseng root displays the ability to achieve glucose homeostasis both experimentally and clinically but the unknown mechanism used by ginseng to achieve its therapeutic effects on diabetes limits its application. Disruption in the insulin secretion of pancreatic β cells is considered the major cause of diabetes. A mitochondrial protein, uncoupling protein‐2 (UCP‐2) has been found to play a critical role in insulin synthesis and β cell survival. Our preliminary studies found that the extracts of American ginseng inhibit UCP‐2 expression which may contribute to the ability of ginseng protecting β cell death and improving insulin synthesis. Therefore, we hypothesized that ginseng extracts suppress UCP‐2 in the mitochondria of pancreatic β cells, promoting insulin synthesis and anti‐apoptosis (a programmed cell‐death mechanism). To test the hypothesis, the serum‐deprived quiescent β cells were cultured with or without interleukin‐1β (IL‐1β), (200 pg ml−1, a cytokine to induce β cell apoptosis) and water extracts of American ginseng (25 μg per 5 μl administered to wells of 0.5 ml culture) for 24 h. We evaluated effects of ginseng on UCP‐2 expression, insulin production, anti‐/pro‐apoptotic factors Bcl‐2/caspase‐9 expression and cellular ATP levels. We found that ginseng suppresses UCP‐2, down‐regulates caspase‐9 while increasing ATP and insulin production/secretion and up‐regulates Bcl‐2, reducing apoptosis. These findings suggest that stimulation of insulin production and prevention of β cell loss by American ginseng extracts can occur via the inhibition of mitochondrial UCP‐2, resulting in increase in the ATP level and the anti‐apoptotic factor Bcl‐2, while down‐regulation of pro‐apoptotic factor caspase‐9 occurs, lowering the occurrence of apoptosis, which support the hypothesis.
Aqueous Extracts of Teucrium polium Possess Remarkable Antioxidant Activity In Vitro
Authors: Ljubuncic Predrag , Dakwar Suha , Portnaya Irina , Cogan Uri , Azaizeh Hassan , Bomzon Arieh
Published: June 2006

Teucrium polium L. (Lamiaceae) (RDC 1117) is a medicinal plant whose species have been used for over 2000 years in traditional medicine due to its diuretic, diaphoretic, tonic, antipyretic, antispasmodic and cholagogic properties. The therapeutic benefit of medicinal plants is often attributed to their antioxidant properties. We previously reported that an aqueous extract of the leaves and stems of this plant could inhibit iron‐induced lipid peroxidation in rat liver homogenate at concentrations that were not toxic to cultured hepatic cells. Others have reported that organic extracts of the aerial components of this plant could inhibit oxidative processes. Against this background, we felt further investigation on the antioxidant action of the extract of T. polium prepared according to traditional Arab medicine was warranted. Accordingly, we assessed (i) its ability to inhibit (a) oxidation of β‐carotene, (b) 2,2′‐azobis(2‐amidinopropan) dihydrochloride (AAPH)‐induced plasma oxidation and (c) iron‐induced lipid peroxidation in rat liver homogenates; (ii) to scavenge the superoxide ($${\hbox{ O }}_{2}^{\bullet ‐}$$) radical and the hydroxyl radical (OH•); (iii) its effects on the enzyme xanthine oxidase activity; (iv) its capacity to bind iron; and (v) its effect on cell glutathione (GSH) homeostasis in cultured Hep G2 cells. We found that the extract (i) inhibited (a) oxidation of β‐carotene, (b) AAPH‐induced plasma oxidation (c) Fe2+‐induced lipid peroxidation in rat liver homogenates (IC50 = 7 ± 2 μg ml−1); (ii) scavenged $${\hbox{ O }}_{2}^{\bullet ‐}$$(IC50 = 12 ± 3 μg ml−1) and OH• (IC50 = 66 ± 20 μg ml−1); (iii) binds iron (IC50 = 79 ± 17 μg ml−1); and (iv) tended to increase intracellular GSH levels resulting in a decrease in the GSSG/GSH ratio. These results demonstrate that the extract prepared from the T. polium possesses antioxidant activity in vitro. Further investigations are needed to verify whether this antioxidant effect occurs in vivo.
Older parents are less responsive to a stressor in a long-lived seabird: a mechanism for increased reproductive performance with age?
Authors: Heidinger Britt J , Nisbet Ian C.T , Ketterson Ellen D
Published: June 2006

In many taxa, reproductive performance increases throughout the lifespan and this may occur in part because older adults invest more in reproduction. The mechanisms that facilitate an increase in reproductive performance with age, however, are poorly understood. In response to stressors, vertebrates release glucocorticoids, which enhance survival but concurrently shift investment away from reproduction. Consequently, when the value of current reproduction is high relative to the value of future reproduction and survival, as it is in older adults, life history theory predicts that the stress response should be suppressed. In this study, we tested the hypothesis that older parents would respond less strongly to a stressor in a natural, breeding population of common terns (
Sterna hirundo
). Common terns are long-lived seabirds and reproductive performance is known to increase throughout the lifespan of this species. As predicted, the maximum level of glucocorticoids released in response to handling stress decreased significantly with age. We suggest that suppression of the stress response may be an important physiological mechanism that facilitates an increase in reproductive performance with age.
Resolving multisensory conflict: a strategy for balancing the costs and benefits of audio-visual integration
Authors: Roach Neil W , Heron James , McGraw Paul V
Published: June 2006

In order to maintain a coherent, unified percept of the external environment, the brain must continuously combine information encoded by our different sensory systems. Contemporary models suggest that multisensory integration produces a weighted average of sensory estimates, where the contribution of each system to the ultimate multisensory percept is governed by the relative reliability of the information it provides (maximum-likelihood estimation). In the present study, we investigate interactions between auditory and visual rate perception, where observers are required to make judgments in one modality while ignoring conflicting rate information presented in the other. We show a gradual transition between partial cue integration and complete cue segregation with increasing inter-modal discrepancy that is inconsistent with mandatory implementation of maximum-likelihood estimation. To explain these findings, we implement a simple Bayesian model of integration that is also able to predict observer performance with novel stimuli. The model assumes that the brain takes into account prior knowledge about the correspondence between auditory and visual rate signals, when determining the degree of integration to implement. This provides a strategy for balancing the benefits accrued by integrating sensory estimates arising from a common source, against the costs of conflating information relating to independent objects or events.
A host-race difference in begging calls of nestling cuckoosCuculus canorusdevelops through experience and increases host provisioning
Authors: Madden Joah R , Davies Nicholas B
Published: June 2006

The structure of common cuckoo nestling begging calls differs between the two host-races parasitizing reed warblers (reed warbler-cuckoos) and dunnocks (dunnock-cuckoos; longer syllable duration, lower peak and maximum frequency, narrower bandwidth). Cross-fostering experiments demonstrated that this difference is not genetically fixed but develops through experience. When newly hatched reed warbler-cuckoos were transferred to dunnock nests, they developed begging calls more like those of dunnock-cuckoos, whereas controls transferred to the nests of robins or left to be raised by reed warblers developed calls more typical of reed warbler-cuckoos. We tested the effectiveness of these different calls in stimulating host provisioning by placing in host nests a single blackbird or song thrush nestling (of similar size to a young cuckoo, but lacking its exuberant begging calls); when it begged we broadcast, from a small loudspeaker on the nest rim, recordings of either dunnock-cuckoo or reed warbler-cuckoo begging calls. Playback of dunnock-cuckoo begging calls induced higher levels of provisioning by dunnocks, whereas playback of reed warbler-cuckoo begging calls did so for both reed warblers and robins. We suggest that the young cuckoo (which ejects the host's eggs/chicks and so is raised alone) learns by experience which calls best stimulate host provisioning.
Overconfidence in wargames: experimental evidence on expectations, aggression, gender and testosterone
Authors: Johnson Dominic D.P , McDermott Rose , Barrett Emily S , Cowden Jonathan , Wrangham Richard , McIntyre Matthew H , Peter Rosen Stephen
Published: June 2006

Overconfidence has long been noted by historians and political scientists as a major cause of war. However, the origins of such overconfidence, and sources of variation, remain poorly understood. Mounting empirical studies now show that mentally healthy people tend to exhibit psychological biases that encourage optimism, collectively known as ‘positive illusions’. Positive illusions are thought to have been adaptive in our evolutionary past because they served to cope with adversity, harden resolve, or bluff opponents. Today, however, positive illusions may contribute to costly conflicts and wars. Testosterone has been proposed as a proximate mediator of positive illusions, given its role in promoting dominance and challenge behaviour, particularly in men. To date, no studies have attempted to link overconfidence, decisions about war, gender, and testosterone. Here we report that, in experimental wargames: (i) people are overconfident about their expectations of success; (ii) those who are more overconfident are more likely to attack; (iii) overconfidence and attacks are more pronounced among males than females; and (iv) testosterone is related to expectations of success, but not within gender, so its influence on overconfidence cannot be distinguished from any other gender specific factor. Overall, these results constitute the first empirical support of recent theoretical work linking overconfidence and war.
Neuropeptide Y in normal eating and in genetic and dietary-induced obesity
Authors: Beck B
Published: June 2006

Neuropeptide Y (NPY) is one the most potent orexigenic peptides found in the brain. It stimulates food intake with a preferential effect on carbohydrate intake. It decreases latency to eat, increases motivation to eat and delays satiety by augmenting meal size. The effects on feeding are mediated through at least two receptors, the Y1 and Y5 receptors. The NPY system for feeding regulation is mostly located in the hypothalamus. It is formed of the arcuate nucleus (ARC), where the peptide is synthesized, and the paraventricular (PVN), dorsomedial (DMN) and ventromedial (VMN) nuclei and perifornical area where it is active. This activity is modulated by the hindbrain and limbic structures. It is dependent on energy availability, e.g. upregulation with food deprivation or restriction, and return to baseline with refeeding. It is also sensitive to diet composition with variable effects of carbohydrates and fats. Leptin signalling and glucose sensing which are directly linked to diet type are the most important factors involved in its regulation. Absence of leptin signalling in obesity models due to gene mutation either at the receptor level, as in the Zucker rat, the Koletsky rat or thedb/dbmouse, or at the peptide level, as inob/obmouse, is associated with increased mRNA abundance, peptide content and/or release in the ARC or PVN. Other genetic obesity models, such as the Otsuka–Long–Evans–Tokushima Fatty rat, the agouti mouse or the tubby mouse, are characterized by a diminution in NPY expression in the ARC nucleus and by a significant increase in the DMN. Further studies are necessary to determine the exact role of NPY in these latter models. Long-term exposure to high-fat or high-energy palatable diets leads to the development of adiposity and is associated with a decrease in hypothalamic NPY content or expression, consistent with the existence of a counter-regulatory mechanism to diminish energy intake and limit obesity development. On the other hand, an overactive NPY system (increased mRNA expression in the ARC associated with an upregulation of the receptors) is characteristic of rats or rodent strains sensitive to dietary-induced obesity. Finally, NPY appears to play an important role in body weight and feeding regulation, and while it does not constitute the only target for drug treatment of obesity, it may nevertheless provide a useful target in conjunction with others.
Phylogeographical history of the widespread meadow fescue (Festuca pratensis Huds.) inferred from chloroplast DNA sequences
Authors: Fjellheim Siri , Rognli Odd Arne , Fosnes Kjetil , Brochmann Christian
Published: June 2006

Aim  Here we explore the variation in chloroplast DNA (cpDNA) in a widespread Eurasian diploid forage grass, meadow fescue (Festuca pratensis Huds.), to address its phylogeographical history. In particular, we aim to answer whether the post‐glacial migration routes of meadow fescue are associated with the spread of agriculture or concurrent with well‐documented natural migration pathways from glacial refugia.

Location  A total of 56 Eurasian accessions of F. pratensis were analysed, representing the entire native distribution area as well as non‐native areas in northernmost Europe.

Methods  Based on initial sequencing of 10 non‐coding cpDNA regions, three regions were sequenced for all F. pratensis accessions. For reference, three closely related species [the diploid Lolium perenne L. and the polyploids Festuca arundinacea Schreb. and Festuca gigantea (L.) Vill.] were also sequenced, as well as the more distantly related Festuca ovina L. Divergence times were estimated assuming a simple molecular clock, calibrated using a previously published estimate of 9 Myr for the divergence between fine‐leaved (F. ovina) and broad‐leaved fescues (F. pratensis, F. arundinacea and F. gigantea).

Results  Limited, but geographically structured, cpDNA variation was observed in F. pratensis. Three haplotypes, estimated to have diverged 0.16 Ma, were identified: one western European (A), one with a wide eastern distribution from central‐eastern Europe into Asia (B) and one Caucasian (C). The haplotypes of the polyploids and L. perenne were estimated to have diverged from haplotype A in F. pratensis 0.8–1.3 Ma.

Main conclusions  We found no definite evidence for migration of the diploid F. pratensis associated with the spread of agriculture from the Fertile Crescent after the last glaciation. The distinct geographical structuring of the present‐day variation in cpDNA can rather be explained by northwards expansion of the western haplotype from an Iberian refugium, expansion of the eastern haplotype from an unlocated (south‐)eastern refugium and glacial survival without subsequent expansion from a Caucasian refugium. The high level of cpDNA divergence observed between this diploid and the polyploids which have probably been derived from it may suggest that the very low level of cpDNA variation in the diploid is caused by a recent bottleneck. Today, F. pratensis is widespread in the open agricultural landscape but appears otherwise confined to naturally open habitats such as river banks, and its populations may have been decimated when dense forests dominated in the previous interglacial.
Are islands more susceptible to plant invasion than continents? A test using Oxalis pes‐caprae L. in the western Mediterranean
Authors: Gimeno Isabel , Vilà Montserrat , Hulme Philip E.
Published: June 2006

Aim  We tested the relative vulnerability of islands to Oxalis pes‐caprae L. invasion compared to mainland regions. Oxalis pes‐caprae is a South African annual geophyte that reproduces via bulbils, and has spread in many Mediterranean and temperate regions of the world where introduced. Our study is one of the first detailed regional analyses of the occurrence and local abundance of a non‐native plant.

Methods  We conducted an extensive survey (2000 sampling points) to examine local and coarse‐scale patterns in both the occurrence and abundance of O. pes‐caprae on islands and in neighbouring mainland regions of Spain.

Location  We analysed occurrence (number of samples where present) and abundance (percentage cover) on two Balearic Islands (Menorca and Mallorca) and in two mainland administrative provinces of Spain (Murcia and València).

Results  Oxalis pes‐caprae occurrence was consistently higher on islands. Occurrence varied among habitats, being the highest in tree groves and the lowest in forests and shrublands. It was never found in these two habitats on the mainland. Mean O. pes‐caprae abundance was greatest in tree groves on the mainland, and in field margins and old fields on the islands. However, in general there were not significant differences in local abundances between island and mainland locations.

Main conclusions  These findings suggest that local processes (such as the biotic resistance of plant communities) are less important than coarse‐scale phenomena (such as environmental driving forces) in explaining differences in the invasion patterns observed between islands and adjacent mainland regions. We suggest that O. pes‐caprae has occupied a larger proportion of available habitats on islands due to: (1) its strong dependence on domestic animal and human‐mediated dispersal which are probably greater on the islands than in mainland areas, and (2) the smaller area encompassed by islands that, over a comparable period of time, enables a greater proportion of available habitats to be colonized (and hence higher occurrence) than equivalent larger mainland areas.
Less diverse forest is more resistant to hurricane disturbance: evidence from montane rain forests in Jamaica
Authors: TANNER E. V. J. , BELLINGHAM P. J.
Published: June 2006

Are more diverse ecosystems more or less resistant to disturbance? Does diversity increase in a forest after being hit by a hurricane? We answer these questions using a 30‐year study of four Jamaican forests, which differ in soil fertility and diversity, and which were hit by Hurricane Gilbert in 1988; the decades were: pre‐Gilbert (1974–84), Gilbert (1984–94), and post‐Gilbert (1994–2004).

Diversity (Shannon index) was always higher in the three forests (Col H′ 3.00, Mull H′ 2.91 and Slope H′ 2.99) on more fertile soils (C : N ratios 10–13, N : P 16–24), and significantly lower in the Mor forest (H′ 2.26) with the least fertile soil (C : N ratio 24, N : P ratio 44). Diversity increased during the Gilbert decade in two of the more diverse forests (Mull and Slope), it did not increase in the least diverse, Mor forest. The overall increase in diversity during the Gilbert decade was due to the recruitment of eight, mostly light‐demanding, species and the increased abundance of uncommon species.

We used turnover rates (the average of mortality and recruitment of stems) as a measure of resistance. We equate low turnover with high resistance to hurricane damage. Turnover increased during the Gilbert decade in all forests, but increased more in the three more diverse forests (Mull 1.5% year−1 1974–84 to 3.1% year−1 1984–94; Slope 1.3–2.6; Col 1.5–3.2); than in the least diverse Mor forest (1.2–1.9).

Stem diameter growth rates pre‐Gilbert were very low in all forests and were lowest in the Mor forest (Mor 0.3 mm year−1, Mull 0.4, Slope 0.5, Col 0.6). They increased during the Gilbert decade and remained, in the post‐Gilbert decade, double those of the pre‐Gilbert decade (Mor 0.6 mm year−1, Mull 0.6, Slope 0.8, Col 1.1). Smaller stems increased growth more than larger stems. The stems recruited during the Gilbert and post‐Gilbert decades grew faster than those present in 1974.

Thus, in montane forest in Jamaica the least diverse forest was most resistant to hurricane damage, and although there was a strong similarity in species rank abundances over 30 years including a hurricane, the hurricane increased diversity.
Bluetongue vector species of Culicoides in Switzerland
Authors: CAGIENARD A. , GRIOT C. , MELLOR P. S. , DENISON E. , STÄRK K. D. C.
Published: June 2006

Abstract Switzerland is historically recognized by the Office Internationale des Epizooties as free from bluetongue disease (BT) because of its latitude and climate. With bluetongue virus (BTV) moving north from the Mediterranean, an entomological survey was conducted in Switzerland in 2003 to assess the potential of the BTV vectors present. A total of 39 cattle farms located in three geographical regions, the Ticino region, the Western region and the region of the Grisons, were monitored during the vector season. Farms were located in areas at high risk of vector introduction and establishment based on the following characteristics: annual average temperature > 12.5°C, average annual humidity ≥ 60%, cattle farm. Onderstepoort black light traps were operated at the cattle farms generally for one night in July and one night in September. A total of 56 collections of Culicoides (Diptera: Ceratopogonidae) were identified morphologically. Only one single individual of Culicoides (Avaritia) imicola, the major Old World vector of BTV, was found in July 2003 in the Ticino region, one of the southernmost regions of Switzerland. In the absence of further specimens of C. imicola from Switzerland it is suggested that this individual may be a vagrant transported by wind from regions to the south of the country where populations of this species are known to occur. Alternative potential BTV vectors of the Culicoides (Culicoides) pulicaris and Culicoides (Avaritia) obsoletus complexes were abundant in all sampled regions with individual catches exceeding 70 000 midges per trap night.
The tick Ixodes ricinus: distribution and climate preferences in the western Palaearctic
Authors: ESTRADA‐PEÑA A. , VENZAL J. M. , SÁNCHEZ ACEDO C.
Published: June 2006

Abstract In this study, multivariate spatial clustering on monthly normalized difference vegetation index (NDVI) maps is used to classify ecological regions over the western Palaearctic. This classification is then used to delineate the distribution and climate preferences of populations (clades) of the tick Ixodes ricinus L. (Acari: Ixodidae) from a geographically extensive dataset of tick records and a gridded 2.5‐km resolution climate dataset. Using monthly layers of the NDVI, regions of similar ecological attributes were defined and nine populations with significant differences in critical climate parameters (P < 0.005) were detected. Grouping of tick records according to other categories, such as political divisions, a 4°× 4° grid overlying the study area, or the CORINE) and USGS) vegetation classification schemes did not provided significantly separated populations (P= 0.094–0.304). Factor analysis and hierarchical tree clustering provided an ecological overview of these tick clades: two Mediterranean and one Scandinavian (western) clades are clearly separated from a node that includes clades of different parts of central Europe and the British Isles, with contrasting affinities between the different clades. The capture records of these ecologically separated clades produce a clear bias when bioclimate envelope modelling is applied to the mapping of habitat suitability for the tick in the western Palaearctic. The best‐performing methods (Cohen’s kappa = 0.834–0.912) use partial models developed with data from each ecoregion, which are then overlapped over the region of study. It is concluded that the use of ecologically derived ecoregions is an objective step in assessing the presence of ecologically different clades, and provides a guide in the development of data partitioning for habitat suitability modelling.
The ‘ghosts’ that pester studies on learning in mosquitoes: guidelines to chase them off
Authors: ALONSO W. J. , SCHUCK‐PAIM C.
Published: June 2006

AbstractThe identification of memory and learning in medically important mosquito species has been of epidemiological interest mainly because of the implications of learning on the pattern of contact between vectors and hosts. Empirical results either showing or suggesting the existence of cognitive abilities in mosquitoes have been reported in a number of experimental studies, mainly based on the observation of individual fidelity towards subsets of specific resources, such as hosts, resting sites or breeding sites. A closer inspection of the design of these experiments shows that, with the exception of recent studies providing stronger evidence of learning in the genus Culex (Diptera: Culicidae), methodological shortcomings still hinder the possibility of eliminating alternative interpretations for these findings, in some cases because the experiments were not specifically designed to identify the phenomenon, but mostly because of a lack of appropriate controls or replication. By highlighting these limitations, while acknowledging the practical difficulties that are inherent to the field, we aim to help expel from future research the ‘ghosts’ that still preclude the achievement of more definite conclusions about the prevalence of memory and learning in this group of insects.
The early interaction between the Caribbean Plateau and the NW South American Plate
Authors: Vallejo Cristian , Spikings Richard A. , Luzieux Leonard , Winkler Wilfried , Chew David , Page Laurence
Published: June 2006

The determination of accurate and precise ages for the timing of collision between oceanic plateaus and continental crust requires an understanding of how the indenting and buttressing plates respond to the collision. We present geochronological, thermochronological, geochemical and isotopic analyses of magmatic rocks from the Ecuadorian Andes, which relate to the collision of the Late Cretaceous Caribbean Plateau and Great Arc sequence with NW South America. The cessation of subduction magmatism during 65–64 Ma beneath the eastern edge of Caribbean Plateau was synchronous with accelerated surface uplift and exhumation within the buttressing continental margin during 75–65 Ma. We interpret this as the collision of the leading edge of the Caribbean Plateau and arc sequence with the South American Plate at 75–65 Ma. A U/Pb (zircon) SHRIMP age of 87.10 ± 1.66 (2σ) Ma, yielded by an accreted fragment of the plateau, precludes previous estimates of collision at 85–80 Ma if the plateau erupted above the Galápagos hotspot.

Terra Nova, 18, 264–269, 2006
The role of EDS1 (enhanced disease susceptibility) during singlet oxygen‐mediated stress responses of Arabidopsis
Authors: Ochsenbein Christian , Przybyla Dominika , Danon Antoine , Landgraf Frank , Göbel Cornelia , Imboden André , Feussner Ivo , Apel Klaus
Published: June 2006

Upon a dark/light shift the conditional flu mutant of Arabidopsis starts to generate singlet oxygen (1O2) that is restricted to the plastid compartment. Distinct sets of genes are activated that are different from those induced by hydrogen peroxide/superoxide. One of the genes that is rapidly upregulated is EDS1 (enhanced disease susceptibility). The EDS1 protein has been shown to be required for the resistance to biotrophic pathogens and the accumulation of salicylic acid (SA) that enhances the defenses of a plant by inducing the synthesis of pathogen‐related (PR) proteins. Because of the similarity of its N‐terminal portion to the catalytic site of lipases, EDS1 has also been implicated with the release of polyunsaturated fatty acids and the subsequent formation of various oxylipins. The release of singlet oxygen in the flu mutant triggers a drastic increase in the concentration of free SA and activates the expression of PR1 and PR5 genes. These changes depend on the activity of EDS1 and are suppressed in flu/eds1 double mutants. Soon after the beginning of singlet oxygen production, the synthesis of oxylipins such as jasmonic acid (JA) and 12‐oxophytodienoic acid (OPDA) also start and plants stop growing and induce a cell‐death response. The inactivation of EDS1 does not affect oxylipin synthesis, growth inhibition and the initiation of cell death, but it does allow plants to recover much faster from singlet oxygen‐mediated growth inhibition and it also suppresses the spread of necrotic lesions in leaves. Hence, singlet oxygen activates a complex stress‐response program with EDS1 playing a key role in initiating and modulating several steps of it. This program includes not only responses to oxidative stress, but also responses known to be activated during plant–pathogen interactions and wounding.
Genetic, physiologic and ecogeographic factors contributing to variation in Homo sapiens: Homo floresiensis reconsidered
Authors: Richards Gary D.
Published: June 2006

A new species, Homo floresiensis, was recently named for Pleistocene hominid remains on Flores, Indonesia. Significant controversy has arisen regarding this species. To address controversial issues and refocus investigations, I examine the affinities of these remains with Homo sapiens. Clarification of problematic issues is sought through an integration of genetic and physiological data on brain ontogeny and evolution. Clarification of the taxonomic value of various ‘primitive’ traits is possible given these data. Based on this evidence and using a H. sapiens morphological template, models are developed to account for the combination of features displayed in the Flores fossils. Given this overview, I find substantial support for the hypothesis that the remains represent a variant of H. sapiens possessing a combined growth hormone–insulin-like growth factor I axis modification and mutation of the MCPH gene family. Further work will be required to determine the extent to which this variant characterized the population.
Photoinactivation of Leishmania donovani infantum in red cell suspensions by a flexible thiopyrylium sensitizer
Authors: Wagner S. J. , Skripchenko A. , Salata J. , Cardo L. J.
Published: June 2006

Background and Objectives  Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania, which are intracellular parasites of monocytes and macrophages. Transmission of the organism has been observed by transfusion of infected blood from asymptomatic donors to immunocompromised recipients, leading to clinically apparent disease. There is no licensed Leishmania screening test currently available.

Materials and Methods  This study investigated the potential for a novel DNA‐intercalating photosensitizer, thiopyrylium (TP), to inactivate Leishmania donovani infantum in red cell (RBC) suspensions.

Results  A 5·7 TCID50 reduction of Leishmania was observed in samples treated with 12·5 µmole l−1 TP and 1·1 J cm−2 light.

Conclusions  Leishmania is highly sensitive to photoinactivation under conditions that have been previously demonstrated to maintain RBC properties during 42 days of storage.
Emmprin (basigin/CD147): Matrix metalloproteinase modulator and multifunctional cell recognition molecule that plays a critical role in cancer progression
Authors: Nabeshima Kazuki , Iwasaki Hiroshi , Koga Kaori , Hojo Hironobu , Suzumiya Junji , Kikuchi Masahiro
Published: June 2006

Emmprin (basigin, CD147) is a cell surface glycoprotein that belongs to the immunoglobulin superfamily. It is highly expressed on the surface of tumor cells and stimulates adjacent fibroblasts or tumor cells to produce matrix metalloproteinases. Moreover, it has recently been shown that emmprin also stimulates expression of vascular endothelial growth factor and hyaluronan, which leads to angiogenesis and anchorage‐independent growth/multidrug resistance, respectively. These findings have made emmprin an important molecule in tumor progression and, thus, more attractive as a target for antitumor treatment. However, other functions of emmprin, including as an activator of T cells, a chaperone for monocarboxylate transporters, a receptor for cyclophilin A and a neural recognition molecule, are also being identified in physiological and pathological conditions. Therefore, it is essential to develop specific means to control particular functions of emmprin, for which elucidation of each mechanism is crucial. This review will discuss the role of emmprin in tumor progression and recent advances in the molecular mechanisms of diverse phenomena regulated by emmprin.
Histopathological approach to prostatic contour alterations with the concept of left–right asymmetry
Authors: Kiyoshima Keijiro , Oda Yoshinao , Tamiya Sadafumi , Hori Yoshifumi , Yamada Tomomi , Naito Seiji , Tsuneyoshi Masazumi
Published: June 2006

It has been suggested that prostate cancer spread has predictable patterns, with prostate cancers known to affect the prostatic contours. However, few systematic investigations have documented the associated contour alterations, especially at a clinically localized stage. The purpose of the present paper was to objectively evaluate prostatic contour alterations based on left–right asymmetry, and analyze the histopathological features and prognostic impact. One hundred and sixty‐two asymmetrical contours with left–right asymmetry in the length ≥10%, and 278 cancer foci were observed in 114 radical prostatectomy specimens. Of the asymmetrical contours, 55 (34%) were caused by cancer, and of the cancer foci, 55 (20%) generated asymmetrical contours. Cancer‐associated asymmetries showed significant correlations with aggressive behaviors such as cancer volume, Gleason score, positive surgical margin, and extraprostatic extension, although these were not significantly associated with unfavorable prognosis. The authors present basic data relating to altered prostatic contours, such as spatial distribution and causative pathological conditions. Clinicopathological characteristics concerning cancer‐associated contour alterations, are also presented in detail.
Jugular foramen chordoid meningioma
Authors: Takei Hidehiro , Rivera Andreana , Suzuki Hiroyoshi , Bahrami Armita , Powell Suzanne Z.
Published: June 2006

Chordoid meningioma (CM) is a rare histological variant of meningioma and is classified as an atypical meningioma on pattern alone. Herein is described the first case of CM occurring in the jugular foramen. The patient was a 45‐year‐old woman with a 2 year history of progressive right hearing loss. Magnetic resonance imaging (MRI) demonstrated a large, dumbbell‐shaped, homogenously gadolinium‐enhanced mass in the right jugular foramen, extending medially to the cerebellopontine angle and caudally into the upper carotid space. Angiographic findings supported a diagnosis of schwannoma. Intraoperatively, the tumor appeared to involve the right glossopharyngeal nerve completely and the vagus nerve incompletely, and was incompletely resected. Microscopically, the tumor consisted predominantly of cords and nests of medium‐sized cells with bland cytological features, surrounded by a pale basophilic mucin. Immunohistochemically, the tumor cells demonstrated reactivity for epithelial membrane antigen (membranous) and vimentin, with negative staining for S‐100 protein, cytokeratin, CD34, glial fibrillary acidic protein (GFAP), synaptophysin, and chromogranin A. Based on the chordoid histology, an organoid lobular arrangement of the tumor cells, and the location of the tumor (jugular foramen), the differential diagnosis included not only a chordoma but also a paraganglioma (glomus jugulare tumor). Histological identification of typical meningotheliomatous areas, plus selective immunohistochemical panel, is important to establish the correct diagnosis.
Severe congestive heart failure with cardiac liver cirrhosis 10 years after orthotopic liver transplantation for familial amyloidotic polyneuropathy
Authors: Sakashita Naomi , Ando Yukio , Haraoka Katsuki , Terazaki Hisayasu , Yamashita Taro , Nakamura Masaaki , Takeya Motohiro
Published: June 2006

Reported herein is an autopsy case of familial amyloidotic polyneuropathy (FAP) with cardiac liver cirrhosis associated with amyloid cardiomyopathy after liver transplantation. At 47 years of age a Japanese woman with a transthyretin Val30Met mutation and sensorimotor polyneuropathy underwent liver transplantation; no postoperative deterioration related to the graft or polyneuropathy occurred. However, cardiovascular dysfunction associated with amyloid deposition gradually worsened. Pacemaker implantation and diuretics were ineffective against the heart failure; 10 years after transplantation the patient died. Autopsy revealed massive pleural and pericardial effusions and amyloid cardiomyopathy, especially in the right atrium and cardiac conduction system. Amyloid deposition was slight in all organs except the heart, but liver cirrhosis with reversed lobulation and centrilobular hemorrhagic necrosis was prominent. There was no histological evidence for chronic liver graft rejection. These findings suggest that liver transplantation effectively stopped amyloid deposition and ameliorated clinical FAP symptoms but that amyloid cardiomyopathy after liver transplantation in advanced clinical stages may lead to severe congestive heart failure and cardiac liver cirrhosis.
Carcinosarcoma of the liver producing granulocyte‐colony stimulating factor
Authors: Aita Kumi , Seki Kunihiko
Published: June 2006

An autopsy case of carcinosarcoma of the liver producing granulocyte‐colony stimulating factor (G‐CSF) is reported. The patient, a 74‐year‐old Japanese man, presented with multiple liver masses. His serum G‐CSF was elevated to 286 pg/mL and a marked leukocytosis of 19 100/µL was observed. The patient had a rapidly aggravated clinical course and died 57 days after admission. Autopsy revealed a liver carcinosarcoma composed both of hepatocellular carcinoma (HCC) and sarcomatous elements immunoreactive with α‐smooth muscle actin and desmin. Immunohistochemistry revealed positive staining of G‐CSF in the cytoplasm of HCC, whereas none of the spindle cells was positively stained. Production of G‐CSF was also confirmed by enzyme‐linked immunosorbent assay, using the frozen tumor tissue taken at the autopsy. Similar to the majority of G‐CSF‐producing tumors in the literature, only the epithelial elements of the present case were immunopositive for G‐CSF. Although a monoclonal origin of carcinosarcomas has generally been proposed, heterologous differentiation from a single clone might lead to the production of G‐CSF only in the epithelial element in the present case. It is suggested that G‐CSF was associated with the high‐grade transformation of the epithelial elements, as well as the reported phenomenon of conventional HCC producing G‐CSF.
Local balance of transforming growth factor‐β1 secreted from cholangiocarcinoma cells and stromal‐derived factor‐1 secreted from stromal fibroblasts is a factor involved in invasion of cholangiocarcinoma
Authors: Ohira Shusaku , Itatsu Keita , Sasaki Motoko , Harada Kenichi , Sato Yasunori , Zen Yoh , Ishikawa Akira , Oda Koji , Nagasaka Tetsuro , Nimura Yuji , Nakanuma Yasuni
Published: June 2006

Tumor–stromal interactions are important for the progression of malignant tumors. The purpose of the present study was to examine interactions of cholangiocarcinoma (CC) cells and stromal fibroblasts with respect to stromal‐derived factor‐1 (SDF‐1) and transforming growth factor (TGF)‐β1. Two cell lines of CC (HuCCT‐1 and CCKS‐1) and WI‐38 fibroblast cell line were used for cell culture, and 12 CC tissue specimens for immunohistochemical studies. Invasion of CC cells was increased significantly by the supernatant from fibroblast cultures, but not by the supernatant from fibroblasts cocultured with CC cells. Expression of SDF‐1 in cultured fibroblasts was downregulated by TGF‐β1 treatment, and coculture with CC cells and anti‐TGF‐β1 neutralizing antibody restored the decreased SDF‐1 expression, suggesting that TGF‐β1 secreted from CC cells might have reduced the expression of SDF‐1 by fibroblasts and might have reduced the increased invasion of CC cells induced by the supernatant from fibroblasts. Immunohistochemical expression of TGF‐β1 in CC cells was focal or negative and that of SDF‐1 was evident in stromal fibroblasts at the invasive front of CC. In conclusion, local mutual influence of TGF‐β1 secreted from carcinoma cells and SDF‐1 expressed by stromal fibroblasts may be involved in invasion of CC cells.
The causes and consequences of rent‐seeking in Northern Ireland, 1945–721
Authors: BROWNLOW GRAHAM
Published: June 2006

Northern Ireland’s economic performance during the ‘golden age’ was weak. Crafts suggested that rent‐seeking was an important determinant of this poor record. This article offers support for such a conclusion. It is suggested that the growth record was shaped by British regulations preventing conflicts of ministerial interest not being made operational until 1963. This institutional divergence tended to promote rent‐seeking behaviour, which impeded the pursuit of an industrial policy that could promote economic efficiency. In 1963 the institutional structure and the industrial policy framework changed. These changes stimulated the pursuit of efficiency and contributed to an improved regional economic performance.
Breeding system variation, genetics and evolution in the Turneraceae
Authors: Shore Joel S. , Arbo Maria M. , Fernández Aveliano
Published: June 2006

We review the genetics and evolution of breeding systems in the Turneraceae. Distyly occurs in seven of 10 genera and 81% of species. The remaining species are homostylous. Polyploid evolution has been significant inTurnera. Approximately 60% of species are polyploid ranging from diploid through decaploid. No relationship between breeding system and polyploidy is evident. The genetics of distyly involves a one‐locus two‐allele system (Sand s). Evidence from crosses with homostylous species and mutants is consistent with the possibility that a ‘Primula‐type’ supergene underlies distyly but does not prove this to be the case. A polygalacturonase, and an α‐dioxygenase specific to the transmitting tissue of short‐styled plants both exhibit morph‐limited expression in concert with predictions from an evolutionary model. The function of the proteins in distyly, if any, is unknown. We have begun constructing a fine‐scale genetic map ofTurnera. Two genetic markers lie within 0.2 cmof the distyly locus. This should provide a starting point for positional cloning of the distyly locus and reveal the genetic architecture and molecular basis of distyly.
Grading infantile cataracts
Authors: Forster J. E. , Abadi R. V. , Muldoon M. , Lloyd I. C.
Published: June 2006

Purpose:  To introduce and describe two methods of grading the severity of infantile cataracts, and thereby propose a useful clinical guide for early surgical intervention.

Methods:  Thirty‐three subjects, aged 1 week to 8 years, participated in the study. Twenty‐two were evaluated soon after birth (1 week), and 11 in childhood (3–8 years). All had isolated infantile cataracts, of which 16 were bilateral and 17 unilateral. Nine cataract types were examined; nuclear (n = 9), lamellar (n = 9), posterior lenticonus (n = 4), persistent hyperplastic primary vitreous (n = 4), posterior polar (n = 3) and single cases of total, cortical, sutural and anterior polar. Grading the infantile cataracts was performed subjectively based on the cataract morphology, density and position using an 11‐point (0–10) ordinal scale. Objective measures of the cataracts were performed by scanning and then digitising photo‐slit lamp images to provide cataract intensity profiles. Subjects without cataracts acted as controls.

Results:  Subjective gradings of 0 and 10 were assigned to the clear, cataract‐free lens and the total cataract, respectively. Fixed grades of 1 (anterior polar, sutural) and 6 (posterior polar) were assigned to the three remaining cataracts with static morphologies. The five cataracts which were all progressive were given grading ranges, reflecting the initial and likely final morphological states. Objective measures were found to be valuable in indicating the exact position and relative density of the cataract, as well as accurately defining boundaries.

Conclusions:  The magnitude and severity of infantile cataracts can be usefully characterised by an 11‐point ordinal subjective grading scale. Although subjective grading alone is satisfactory, it can be greatly assisted by objective measures, particularly in the documentation of cataract progression. Cataracts assigned grades 1–4 were considered minor obstructions to vision and therefore not candidates for early surgery. Cataracts graded 5 and above were considered major visual defects, and ideally should be removed early in life.
Visual impairment and the useful field of vision
Authors: Leat Susan J. , Lovie‐Kitchin Jan
Published: June 2006

The aim of this study was to measure the useful field of vision (UFoV) in people with visual impairment and to compare results with clinical measures of vision. UFoV, visual acuity, contrast sensitivity and visual fields were measured in 36 participants with low vision and 22 age‐matched controls in two age groups. For both the low vision and control groups the presence of distractors (cluttered field) increased the error rates on our UFoV measure but there was no significant effect of the presence of a central task (divided attention). Participants with low vision made more errors on UFoV than did controls, but this difference disappeared once their visual field defects were accounted for. By multiple regression analysis, age, visual fields and contrast sensitivity were shown to predict the different UFoV scores. As for observers with normal vision, standard clinical visual field tests may not fully describe the difficulties that may be encountered by people with visual impairment undertaking tasks in the cluttered environments and multiple demands of everday life.