bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of coffee alkaloids and phenolics on egg-laying by the coffee leaf minerLeucoptera coffeella
Authors: Magalhães S.T.V. , Guedes R.N.C. , Demuner A.J. , Lima E.R.
Published: June 2008

The recognized importance of coffee alkaloids and phenolics mediating insect-plant interactions led to the present investigation aiming to test the hypothesis that the phenolics chlorogenic and caffeic acids and the alkaloid caffeine and some of its derivatives present in coffee leaves affect egg-laying by the coffee leaf minerLeucoptera(=Perileucoptera)coffeella(Guérin-Méneville & Perrottet) (Lepidoptera: Lyonetiidae), one of the main coffee pests in the Neotropical region. These phytochemicals were, therefore, quantified in leaves from 12 coffee genotypes and their effect on the egg-laying preference by the coffee leaf miner was assessed. Canonical variate analysis and partial canonical correlation provided evidence that increased leaf levels of caffeine favour egg-laying by the coffee leaf miner. An egg-laying preference bioassay was, therefore, carried out to specifically test this hypothesis using increasing caffeine concentrations sprayed on leaves of one of the coffee genotypes with the lowest level of this compound (i.e. Hybrid UFV 557-04 generated from a cross betweenCoffea racemosaLour. andC. arabicaL.). The results obtained allowed the recognition of a significant concentration-response relationship, providing support for the hypothesis that caffeine stimulates egg-laying by the coffee leaf miner in coffee leaves.
Exon-primed intron-crossing (EPIC) PCR markers ofHelicoverpa armigera(Lepidoptera: Noctuidae)
Authors: Tay W.T. , Behere G.T. , Heckel D.G. , Lee S.F. , Batterham P.
Published: June 2008

Applying microsatellite DNA markers in population genetic studies of the pest mothHelicoverpa armigerais subject to numerous technical problems, such as the high frequency of null alleles, occurrence of size homoplasy, presence of multiple copies of flanking sequence in the genome and the lack of PCR amplification robustness between populations. To overcome these difficulties, we developed exon-primed intron-crossing (EPIC) nuclear DNA markers forH. armigerabased on ribosomal protein (Rp) and the Dopa Decarboxylase (DDC) genes and sequenced alleles showing length polymorphisms. Allele length polymorphisms were usually from random indels (insertions or deletions) within introns, although variation of short dinucleotide DNA repeat units was also detected. Mapping crosses demonstrated Mendelian inheritance patterns for these EPIC markers and the absence of both null alleles and allele ‘dropouts’. Three examples of allele size homoplasies due to indels were detected in EPIC markers RpL3, RpS6 and DDC, while sequencing of multiple individuals across 11 randomly selected alleles did not detect indel size homoplasies. The robustness of the EPIC-PCR markers was demonstrated by PCR amplification in the related species,H. zea,H. assultaandH. punctigera.
Two mitochondrial lineages occur in the Asian corn borer,Ostrinia furnacalis(Lepidoptera: Crambidae), in Japan
Authors: Hoshizaki S. , Washimori R. , Kubota S. , Ohno S. , Huang Y. , Tatsuki S. , Ishikawa Y.
Published: June 2008

The genealogy and diversity of the mitochondrial cytochrome oxidase subunit II (COII) gene were investigated forOstrinia furnacalisin Japan. A preliminary examination of mitochondrial lineages in China and the Philippines was also made. Two lineages (A and B) were found in the COII gene. Lineage A was frequent throughout the Japanese main islands (Hokkaido, Honshu, Shikoku and Kyushu), while the frequency of lineage B varied among these islands. No clear patterns of geographical population structure were found. Population genetic features suggested that theO. furnacalispopulation harboring the lineage A mitochondria expanded in the recent past, while lineage B showed weak signals of a population expansion. It is not clear whether the two lineages of mtDNA evolved in separate or identical geographical regions. We discuss two hypotheses regarding the two lineages of mtDNA: a cryptic race/species hypothesis and a selective sweep hypothesis.
Petrogenesis of albite-rich mid- to late Proterozoic tephra-fall deposits (‘brown beds’)
Authors: BATCHELOR RICHARD A. , PRAVE ANTHONY R. , OLIVER GRAHAME J. H. , RAEBURN ANDREW S.
Published: June 2008

The discovery of volcanogenic ‘brown beds’ in Dalradian and Torridonian (Sleat Group and Diabaig Group) sequences in Scotland has raised questions about their origin and provenance. New discoveries of a grey facies cognate to the ‘brown beds’ have led to an hypothesis which proposes that these beds originated as tephra-fall deposits of intermediate to mafic composition. Subsequent prehnite–pumpellyite- and greenschist-facies metamorphism generated an albite–chlorite–muscovite–quartz–calcite assemblage. Recent sub-aerial weathering selectively dissolved interstitial calcite and oxidized iron, which left an albite-rich ‘brown bed’ with a porous saccharoidal texture. Field relationships and mineralogy support their origin as tephra-fall deposits and their widespread occurrence suggests they are not localized phenomena. Crucially, the weathered ‘brown beds’ point to the existence of otherwise cryptic grey metamorphosed tuffs which tend to blend in with their host metasediments.
Onset of coherent electromagnetic structures in the relativistic electron beam deuterium-tritium fuel interaction of fast ignition concern
Authors: Deutsch C. , Bret A. , Firpo M.-C. , Gremillet L. , Lefebvre E. , Lifschitz A.
Published: June 2008

We focus attention on the combinations of swiftly growing electromagnetic instabilities (EMI) arising in the interaction of relativistic electron beams (REB) with precompressed deuterium-tritium (DT) fuels of fast ignition interest for inertial confinement fusion (ICF). REB-target system is taken neutral in charge and current with distribution functions including target and beam temperatures. We stress also the significant impact on modes growth rates (GR) of mode-mode coupling and intrabeam scattering. Collisional damping is documented at large wave numbers in terms of inverse skin depth. A quasi-linear approach yields lower GR than linear ones. One of the most conspicuous output of the linear analysis are three-dimensional (3D) broken ridges featuring the largest GR above k-space for an oblique propagation w.r.t initial particle beam direction. The given modes are seen immune to any temperature induced damping. Those novel patterns are easily produced by considering simultaneously Weibel, filamentation and two-stream instabilities. The behaviors persist in the presence of smooth density gradients or strong applied magnetic fields. Moreover, in the very early propagation stage with no current neutralization in the presence of large edge density gradients, REB demonstrate a characteristics ringlike and regularly spiked pattern in agreement with recent experimental results and previous simulations.
PALS laser energy transfer into solid targets and its dependence on the lens focal point position with respect to the target surface
Authors: Kasperczuk A. , Pisarczyk T. , Kalal M. , Martinkova M. , Ullschmied J. , Krousky E. , Masek K. , Pfeifer M. , Rohlena K. , Skala J. , Pisarczyk P.
Published: June 2008

This paper is devoted to investigations of laser energy transfer into solid targets with respect to the focusing lens focal point position relative to the solid target surface as obtained at the PALS laser facility. The third harmonic of the PALS laser beam with energy ~90 J and pulse duration ~250 ps (FWHM) was used for irradiation of two kinds of targets made of Cu: a slab and a 3.6 µm thick foil. The focal point of the beam was located either inside or in front of the target surface, and care was taken to ensure the same laser spot radii in both cases (250 µm). It was demonstrated that these two opposite focal point positions give rise to significantly different laser-plasma interactions: with either depression or maximum of the laser intensity distribution in the center of the beam, respectively. It was also verified that the focal point position inside of the target is favorable for plasma jets creation, whereas the opposite case is more effective for acceleration of flyers.
High energy density and beam induced stress related issues in solid graphite Super-FRS fast extraction targets
Authors: Tahir N.A. , Kim V.V. , Matvechev A.V. , Ostrik A.V. , Shutov A.V. , Lomonosov I.V. , Piriz A.R. , Lopez Cela J.J. , Hoffmann D.H.H.
Published: June 2008

Survival of the production target in successive experiments (with a repetition rate of 1 Hz) over an extended period of time is one of the key problems encountered in designing the Super-FRS (Superconducting Fragment Separator) at the future Facility forAntiprotons and Ion Research (FAIR). Because of the difficulties involved in construction of a liquid jet metal target, it is highly desirable to employ a solid production target at the Super-FRS. However, with the high beam intensities that will be available at the FAIR, the production target may be destroyed in a single experiment due to high specific energy deposition by the beam in the target material. The level of specific energy deposition can be reduced to an acceptable value by increasing the beam focal spot area. However, the spot size is limited by requirements of achieving good isotope resolution and sufficient transmission of the secondary beam through the system. The resolving power of the fragment separator is inversely proportional to the X-dimension of the focal spot whereas the transmission depends on Y-dimension only. It has been previously shown [Tahir et al., 2005c] that an elliptic focal spot with appropriate dimensions, will fulfill the above two conditions simultaneously and will also have a large enough area to reduce the specific energy deposition to an acceptable level for certain beam intensities of interest. In this paper we present numerical simulations of thermodynamic and hydrodynamic behavior of a solid graphite target that is irradiated by 1 GeV/u uranium beam in the intensity range of 1010 –1011 ions per bunch with a bunch length = 50 ns. These simulations have been carried out using a three-dimensional computer code, PIC3D, that includes elastic-plastic effects. This theoretical work has shown that up to a beam intensity of 1011 ions/bunch, one can employ a solid target while for higher intensities the target will be destroyed due to thermal stresses induced by the beam. It has also been found that a circular focal spot leads to minimum thermal stresses as it generates minimum pressure gradients compared to an elliptic focal spot, for the same specific energy deposition. Moreover, the stress level increases with an increase in the ellipticity of the focal spot. It is therefore recommended that one should use a circular focal spot for lower intensities provided that the criteria for isotope resolution and transmission are fulfilled.
Photon wave mechanics in the eikonal limit: Diamagnetic field-plasma interaction
Authors: Keller O.
Published: June 2008

A microscopic eikonal theory based on photon wave mechanics is established. The diamagnetic (solid state) field-plasma interaction is shown to play a central role in the theory, and this interaction enables one to introduce a massive transverse photon concept. This quasi-particle enters the eikonal theory in manner similar to the one in which the classical point particle enters Newtonian Mechanics in the Hamilton-Jacobi formulation. When the spatial fluctuations in the stationary-state plasma density are of importance the microscopic eikonal theory becomes a spatially nonlocal theory, and the nonlocality, originating in the coupling of longitudinal and scalar photons to the massive transverse photon, extends over near-field distances.
Corruption in Transitional China: An Empirical Analysis
Authors: Guo Yong
Published: June 2008

Based on an evaluation of three methods adopted by current empirical analysis of corruption, this article argues for a statistical analysis method of studying corruption cases. It adopts three new indicators: the latency period of corruption, the number of newly occurring corruption cases and the cumulative number of cases. By applying these indicators to an analysis of 594 major corruption cases, the article develops a new method to describe the position of corruption in transitional China, and presents new evidence on characteristics and trends of corruption and its relation with China's economic transition.
Studies of Contemporary Chinese Politics in Korea: An Assessment
Authors: Ho Chung Jae
Published: June 2008

Given the extraordinary pace of across-the-board expansion in Korea–China relations, the lack of assessments on the state of studies of contemporary Chinese politics in Korea is a crucial void to be filled. This evaluative article first offers a socio-demographic sketch of the Korean scholarly community of contemporary Chinese politics. More specifically, it examines how the epistemological community has evolved over the last half century in terms of generational and orientational changes. The second section assesses scholarly outputs in the field of contemporary Chinese politics by looking at monographs, refereed journal articles and doctoral dissertations produced by Korean scholars. The article concludes with some suggestions for further advancement of the studies of contemporary Chinese politics, which may be applicable to Korea as well as to the peer communities in other countries.
Population census of Cook's Petrel Pterodroma cookii breeding on Codfish Island (New Zealand) and the global conservation status of the species
Authors: Rayner Matt J. , Parker Kevin A. , Imber Michael J.
Published: June 2008

Codfish Island is the southernmost breeding location for Cook's Petrel (Pterodroma cookii), endemic to the New Zealand archipelago. To provide a population estimate and indication of population growth following introduced predator eradications we conducted an island-wide survey of Codfish Island within two a priori defined strata. Plot surveys revealed only five burrows within forest habitats from 175 plots surveyed and the locations of these and other burrows observed incidentally were used to identify three key areas of Cook's Petrel breeding activity that were subsequently surveyed using line transects. Within these areas, 42 burrows were counted with burrow densities ranging from 0.0003 to 0.002 burrows m−2. Burrow densities in conjunction with the three-dimensional surface areas of the surveyed locations suggested a minimum of 6,194 ± 956 burrows present and equated to approximately 5,000 (95% CI 3,000–6,000) breeding pairs, using a burrow occupancy estimate of 80%. The Cook's Petrel population on Codfish Island appears to have increased markedly since Weka (Gallirallis australis ) and Pacific Rat (Rattus exulans) were eradicated in 1980 and 1998 and is consistent with a recent upwards revision of the species' world population size of approximately 1,300,000 (900,000–1,800,000) individuals. Revised population data, and ongoing protection of Cook's Petrel's major breeding sites may now qualify the species for a revised conservation status moving from Endangered to Vulnerable under IUCN criteria.
Status review of Belding's Yellowthroat Geothlypis beldingi, and implications for its conservation
Authors: Erickson Richard A. , Hamilton Robert A. , Mlodinow Steven G.
Published: June 2008

Belding's Yellowthroat (Geothlypis beldingi) inhabits freshwater marshes the length of the state of Baja California Sur. A gap in occurrence from approximately 25°50′N to 24°50′N separates the subspecies goldmani to the north from beldingi to the south. According to BirdLife International's (2000, 2007) population estimates, the most important sites for the species are San Ignacio (537–648 birds) and La Purísima (203–450) in the north and San José del Cabo (219–480) and Punta San Pedro (70) in the south. Half of 12 presumed breeding sites in the north and five of 14 in the south were discovered within the last ten years. The species apparently no longer occurs at one historical site in the south. Since 2000, two records from Guerrero Negro and one from Bahía Tortugas approximately 140 km and > 200 km respectively northwest of the known breeding range demonstrate the species' dispersal ability. Belding's Yellowthroat is of utmost conservation concern, but the most recent conservation summaries exaggerated the species' plight, in particular by under-appreciating the bird's capacity for long-range dispersal and the ability of marsh habitat to regenerate quickly. Formal studies of the species should be undertaken and marsh creation should be incorporated in the state's development plans. Previous calls for reintroduction efforts should not be heeded, at least for the time being.
Biometrics as a determinant of the origins of seabirds killed in oil spills and other incidents
Authors: Barrett Robert T. , Anker-Nilssen Tycho , Bakken Vidar , Strøm Hallvard , Krasnov Yuri , Aarvak Tomas
Published: June 2008

Common Guillemots Uria aalge and Brünnich's Guillemots U. lomvia are common victims of oil spills, drowning in fishing nets and winter wrecks. Because the Norwegian population of Common Guillemots is classified as critically endangered and the Russian population of the Brünnich's Guillemot has declined greatly, it is important to be able to identify the origins of birds killed outside the breeding season. Measurements of birds made in nine colonies in the Barents and Norwegian Seas showed that although it is impossible to determine with reasonable accuracy the colony of origin from body measurements, the most likely sea of origin of Common Guillemots may be determined on the basis of wing and head + bill lengths, whereas there was no systematic variation in any measurement of Brünnich's Guillemots.
Roosting behaviour of the endangered Sichuan Hill-partridge Arborophila rufipectus during the breeding season
Authors: Liao Wenbo , Hu Jinchu , Li Cao , Lu Xin
Published: June 2008

Roosting behaviour in diurnal ground-dwelling birds is important to their conservation as they are particularly vulnerable to predation when on their roosts. In 2005, we studied the roosting behaviour of the globally ‘Endangered’ Sichuan Hill-partridge (Arborophila rufipectus) in Laojunshan Nature Reserve, southwest China, a site dominated by evergreen broadleaf forest. Our study showed that the birds roosted on elevated perches and roosting behaviour was associated with social organization. Breeding males roosted alone within their territories before mating or during the female's involvement in incubation, but at other times they roosted with the female bird. After hatching of the brood, the adult males roosted on the ground close to the brooding female for about two weeks. After this time the male left the female and chicks to roost elsewhere in the territory. High vegetation cover around the perch site was a key predictor of roosting sites for the partridges. Only six out of 84 tree and shrub species were typically used by the roosting birds, although individual roosting plants varied from night to night. The median height of roosting plants was 6.9 (3.8–10.5) m, which was significantly lower than many shrubs within the breeding territory. Perches were 1.7–6.4 (median = 2.7) m from the ground and independent of roost tree height, suggesting an optimum roosting height. The partridges preferred roosting sites with denser shrub vegetation. In terms of the species' conservation, our results highlight the importance of protecting primary forest that contains suitable roosting trees and shrubs.
High variation in roost use by Dunlin wintering in California: Implications for habitat limitation
Authors: Conklin Jesse R. , Colwell Mark. A , Fox-Fernandez Nancy W.
Published: June 2008

Effective shorebird conservation requires a greater understanding of use and availability of high-tide roosts in coastal non-breeding areas. In this paper, we explore 1) variation in use of roosts; 2) landscape and environmental correlates of roost use; and 3) responses to predators and humans at roosts, to evaluate roost availability for a wintering population of Dunlin Calidris alpina pacifica at Humboldt Bay, CA, USA. For four winters (2002–2005), Dunlin use of particular roosts was highly variable at the population and individual level, even at the most-used roosts. In any given day, week, or month, most Dunlin roosts were unused, and we continued to record new roosts even in the fourth year of study. Although roost use was influenced by landscape attributes, time of day, and environmental conditions, these variables left most variation in roost use unexplained. Dunlin departures from roosts were associated with the presence of avian predators, but not with human activity. Collectively, these observations revealed no strong evidence that roost availability was limited. This contrasts with findings of other studies, even after considering differences in methodology and spatial scale of analysis. We discuss implications for the interpretation of movement data, protection and/or creation of roosting habitat, and assessment of roost quality.
The Weight and Hopcount of the Shortest Path in the Complete Graph with Exponential Weights
Authors: HOOGHIEMSTRA GERARD , VAN MIEGHEM PIET
Published: June 2008

Both the hopcount HN (the number of links) and the weight WN (the sum of the weights on links) of the shortest path between two arbitrary nodes in the complete graph KN with i.i.d. exponential link weights is computed. We consider the joint distribution of the pair (HN, WN) and derive, after proper scaling, the joint limiting distribution. One of the results is that HN and WN, properly scaled, are asymptotically independent.
Genetic diversity in the USDA Limnanthes germplasm collection assessed by simple sequence repeats
Authors: Donnelly Linda M. , Jenderek Maria M. , Prince James P. , Reeves Patrick A. , Brown Allan , Hannan Richard M.
Published: June 2008

The genus Limnanthes (Limnanthaceae), also known as meadowfoam, has attracted attention for industrial use due to the unique characteristics of its seed oil. Samples from wild populations showed variability in agronomically important traits involved in seed oil yield, warranting the establishment and continued development of a germplasm collection. The level of genetic diversity within the United States Department of Agriculture, Agriculture Research Service, National Plant Germplasm System (USDA-ARS-NPGS) Limnanthes collection was evaluated using 15 simple sequence repeat (SSR) markers across 62 accessions representing 7 species. Parsimony analysis separated the accessions into two main groups consistent with the traditional taxonomic sections Inflexae and Reflexae, but there was little resolution within groups. These two groups were confirmed using neighbour-joining analysis and principal coordinate analysis. SSR marker variation suggests that the Limnanthes germplasm collection is genetically diverse and the accessions within the species likely contain novel alleles, and therefore the collection contributes to the conservation of the wild Limnanthes gene pool.
Technoscience Art: A Bridge between Neuroesthetics and Art History?
Authors: Salah Alkım Almıla Akdağ , Salah Albert Ali
Published: June 2008

One of the most exciting recent developments in mainstream art history is its confrontation with the cognitive sciences and neurology. This study is based on the problems these disciplines face before they can contribute to each other. The authors inspect several critical issues resulting from this encounter, especially in the new field of neuroesthetics. The authors argue that it is a language barrier between the disciplines, rather than any fundamental conceptual division, that causes the lack of understanding on both sides. Shared terms in arts and neuroscience are elusive, and the different connotations of extant terms in these separate disciplines must be addressed. The authors propose technoscience art as a ground in which joint terminology may be developed, an audience familiar to the concerns of both sides can be formed, and a new generation of scientifically knowledgeable artists and scientists can interact for their mutual benefit.
Neuroscience, the Food of Musical Culture?
Authors: Margulis Elizabeth Hellmuth
Published: June 2008

Music has received enough recent attention from researchers seeking to understand the brain to be called “the food of neuroscience” ( R. J. Zatorre & J. McGill, 2005 ). The dissemination of research on the neuroscience of music, through both popular and academic channels, has the potential to shape the cultural conceptualization of music. This paper considers the impact of neuroscientific approaches to music on the ways that music is practiced and thought about.
Genes, Brains, and Language: An Epistemological Examination of how Genes can Underlie Human Cognitive Behavior
Authors: Gontier Nathalie
Published: June 2008

How do genes encode for the formation of morphological structures such as the brain? Can genetic material also encode for behavior such as cognition, language, or culture? For many years, evolutionary biologists as well as scholars who work within extrabiological fields such as psychology, linguistics, and archaeology could only answer the above two questions in a speculative manner. This is because until recently, empirical observations on how genes underlie anatomy or behavior were generally lacking. This situation has now changed. Several genes ( MCPH1-MCPH6) have been implicated in the regulation of brain size and a first gene (the FOXP2 gene) has been identified that might underlie linguistic behavior. These discoveries allow us to finally test some of the long-standing theoretical assumptions on how genes do or do not determine morphology and behavior.
Dualism Redux in Recent Neuroscience: “Theory of Mind” and “Embodied Simulation” Hypotheses in Light of Historical Debates about Perception, Cognition, and Mind
Authors: Kerr Catherine E.
Published: June 2008

How do we, as humans, take in the feelings and thoughts of other people? Theory-of-Mind (ToM) and Embodied Simulation (ES) approaches hypothesize divergent neural and behavioral mechanisms underlying intersubjectivity. ToM investigators assert that humans take in the belief states and intentions of another person by holding “a theory of mind” that cognitively posits the other person's mental contents, with some experiments identifying the right temporo-parietal junction as a specific ToM brain region. ES theorists hypothesize that humans perceive the other's state of mind by simulating his/her actions, emotions, and goals in the “mirror neuron system” in the brain.

A historical review suggests these understandings rely on opposing, dualist models of cognition and perception. William James's intervention on this earlier debate is informative in anticipating recent findings in low-level sensory neuroscience. Of specific interest are studies showing that intersubjectivity and low-level sensory attentional filtering are both processed in the same cortical area (the temporo-parietal junction) suggesting that the ability to entertain other minds may be related to the ability to perceive salient stimuli during attention-demanding tasks.
Cannabinoids reduce granuloma‐associated angiogenesis in rats by controlling transcription and expression of mast cell protease‐5
Authors: De Filippis D , Russo A , D'Amico A , Esposito G , Concetta P , Cinelli M , Russo G , Iuvone T
Published: June 2008

Background and purpose:

Chronic inflammatory conditions, such as granulomas, are associated with angiogenesis. Mast cells represent the main cell type orchestrating angiogenesis, through the release of their granule content. Therefore, compounds able to modulate mast cell behaviour may be considered as a new pharmacological approach to treat angiogenesis‐dependent events. Here, we tested the effect of selective cannabinoid (CB) receptor agonists in a model of angiogenesis‐dependent granuloma formation induced by λ‐carrageenin in rats.

Experimental approach:

Granulomas were induced by λ‐carrageenin‐soaked sponges implanted subcutaneously on the back of male Wistar rats. After 96 h, implants were removed and granuloma formation was measured (wet weight); angiogenesis was evaluated by histological analysis and by the measurement of haemoglobin content. Mast cells in the granulomas were evaluated histologically and by RT‐PCR and immunoblotting analysis for mast cell‐derived proteins (rat mast cell protease‐5 (rMCP‐5) and nerve growth factor). Selective CB1 and CB2 receptor agonists, ACEA and JWH‐015 (0.001–0.1 mg mL−1), were given locally only once, at the time of implantation.

Key results:

The CB1 and CB2 receptor agonists decreased the weight and vascularization of granulomas after 96 h. This treatment also reduced mast cell number and activation in granulomatous tissue. Specifically, these compounds prevented the transcription and expression of rMCP‐5, a protein involved in sprouting and advance of new blood vessels.

Conclusion and implications:

Modulation of mast cell function by cannabinoids reduced granuloma formation and associated angiogenesis. Therefore cannabinoid‐related drugs may be useful in the management of granulomatous diseases accompanied by angiogenesis.

British Journal of Pharmacology (2008) 154, 1672–1679; doi:10.1038/bjp.2008.211; published online 16 June 2008
Oxytocin‐induced contractions within rat and rabbit ejaculatory tissues are mediated by vasopressin V1Areceptors and not oxytocin receptors
Authors: Gupta J , Russell R J , Wayman C P , Hurley D , Jackson V M
Published: June 2008

Background and purpose:

Oxytocin is believed to be involved in ejaculation by increasing sperm number and contracting ejaculatory tissues. However, oxytocin may mediate these effects via oxytocin or vasopressin (AVP) receptors. The aim of this study was to determine the effect of oxytocin and AVP on peripheral tissues involved in ejaculation and to identify the receptor subtype(s) involved.

Experimental approach:

Standard tissue bath techniques were used to measure isometric tension from tissues involved in ejaculation and erection.

Key results:

Oxytocin and AVP failed to elicit a tonic contractile response in rat and rabbit testes, vas deferens, epididymis, seminal vesicles and prostate. In contrast, oxytocin and AVP elicited large tonic contractions in erectile (corpus spongiosum and corpus cavernosum) and ejaculatory (prostatic urethra, bladder neck and ejaculatory duct) tissues in a concentration‐dependent manner. The selective oxytocin agonist, [Thr4,Gly7]‐oxytocin and the V2agonist, [deamino‐Cys1,Val4,D‐Arg8]‐vasopressin (dDAVP), failed to contract tissues. Oxytocin and AVP‐induced contractions were weakly antagonized by the selective oxytocin antagonist, L‐368899 but potently antagonized by the V1Aantagonist, SR49059. The V1Bantagonist SSR149415 failed to antagonize AVP contractions except in rabbit bladder neck. Neither L‐368899 nor SR49059 antagonized endothelin‐1‐induced contractions.

Conclusions and implications:

The contractile effect of oxytocin on rat and rabbit ejaculatory and erectile tissues is mediated via V1Areceptors. Endothelin‐1‐induced contractions are not due to endogenous oxytocin or AVP release. V1Areceptor antagonists may have a therapeutic role in both erectile dysfunction and premature ejaculation.

British Journal of Pharmacology(2008)155, 118–126; doi:10.1038/bjp.2008.226; published online 16 June 2008
A dose escalation study in sheep of the effects of the benzodiazepine CNS 7056 on sedation, the EEG and the respiratory and cardiovascular systems
Authors: Upton R N , Martinez A M , Grant C
Published: June 2008

Background and purpose:

CNS 7056 is a new, rapidly metabolized benzodiazepine. The effects of escalating doses of CNS 7056 on sedation, and respiratory and cardiovascular function, were examined in conscious, chronically instrumented sheep for the first time.

Experimental approach:

Three sheep were given doses of CNS 7056 (0, 0.037, 0.074, 0.18, 0.37, 0.74, 2.21, 4.41 and 8.82 mg kg−1) as 2 min intravenous infusions in order on consecutive days. A range of physiological variables, including the EEG, were measured.

Key results:

Sheep became transiently drowsy for the lowest (0.037 and 0.074 mg kg−1) doses of CNS 7056, whereas the highest (8.82 mg kg−1) dose produced profound loss of consciousness (LOC) for over 30 min. The EEG alpha power correlated well (r=0.91) with duration of LOC and had a high signal‐to‐noise ratio. CNS 7056 reduced respiratory rate (maximum 33%) and dose‐dependently increased arterial carbon dioxide tension (maximum 12%). There was a transient, dose‐related reduction in arterial oxygen tension (maximum 34%), but haemoglobin desaturation was minimal (maximum 4%). CNS 7056 produced a dose‐related transient drop in mean arterial blood pressure (maximum 12%) but cardiac output was unchanged.

Conclusions and implications:

Doses of 0.37–2.21 mg kg−1 of CNS 7056 produced sedation for 9–25 min without excessive respiratory or cardiovascular depression, and would be suitable for pharmacokinetic studies. The power in the alpha band of the EEG can be used as a continuous measure of the sedative effects of CNS 7056.

British Journal of Pharmacology (2008) 155, 52–61; doi:10.1038/bjp.2008.228; published online 16 June 2008
Low concentrations of tetrodotoxin interact with tetrodotoxin‐resistant voltage‐gated sodium channels
Authors: Farmer C E , Smith K J , Docherty R J
Published: June 2008

Background and purpose:

Tetrodotoxin (TTX) is used to distinguish between two classes of voltage‐gated sodium channel (VGSC)—TTX sensitive (TTXS) and TTX resistant (TTXR). The resistance of TTXR VGSCs is thought to result from a low binding affinity of TTX, although at high TTX concentrations channel block does occur. Here, we show that, at concentrations below those which produce block, TTX can bind to TTXR VGSCs.

Experimental approach:

Whole‐cell voltage clamp recordings were made from dissociated rat dorsal root ganglion neurones that expressed both TTXS and TTXR sodium currents. Voltage‐gated calcium currents were blocked by 10 μM extracellular lanthanum chloride. TTXS, but not TTXR, current was suppressed by using a holding potential of −50 mV, and the effect of TTX on the isolated TTXR current was explored.

Key results:

Extracellular application of 0.5 μM TTX produced a 40% increase in TTXR current amplitude, a negative shift in the voltage‐dependence of current activation (approximately −8 mV) and inactivation (approximately −10 mV) and increased rates of current activation and inactivation. The effect of TTX on current amplitude was dose‐dependent (EC50=364 nM). Removal of lanthanum prevented the effect of TTX on TTXR current amplitude, whereas reducing extracellular calcium did not.

Conclusions and implications:

The findings are consistent with an interpretation that TTX relieves a tonic block of the TTXR VGSC by lanthanum. We conclude that TTX binds to the TTXR VGSC at low concentrations, without blocking it. This appears to be the first demonstration of a clear distinction between binding affinity and blocking potency of a channel‐blocking agent.

British Journal of Pharmacology (2008) 155, 34–43; doi:10.1038/bjp.2008.235; published online 16 June 2008
Inhibition of fatty acid amide hydrolase by kaempferol and related naturally occurring flavonoids
Authors: Thors L , Belghiti M , Fowler C J
Published: June 2008

Background and purpose:

Recent studies have demonstrated that the naturally occurring isoflavone compounds genistein and daidzein inhibit the hydrolysis of anandamide by fatty acid amide hydrolase (FAAH) in the low micromolar concentration range. The purpose of the present study was to determine whether this property is shared by flavonoids.

Experimental approach:

The hydrolysis of anandamide in homogenates and intact cells was measured using the substrate labelled in the ethanolamine part of the molecule.

Key results:

Twenty compounds were tested. Among the commonly occurring flavonoids, kaempferol was the most potent, inhibiting FAAH in a competitive manner with a Ki value of 5 μM. Among flavonoids with a more restricted distribution in nature, the two most active toward FAAH were 7‐hydroxyflavone (IC50 value of 0.5–1 μM depending on the solvent used) and 3,7‐dihydroxyflavone (IC50 value 2.2 μM). All three compounds reduced the FAAH‐dependent uptake of anandamide and its metabolism by intact RBL2H3 basophilic leukaemia cells.

Conclusions and implications:

Inhibition of FAAH is an additional in vitro biochemical property of flavonoids. Kaempferol, 7‐hydroxyflavone and 3,7‐dihydroxyflavone may be useful as templates for the synthesis of novel compounds, which target several systems that are involved in the control of inflammation and cancer.

British Journal of Pharmacology (2008) 155, 244–252; doi:10.1038/bjp.2008.237; published online 16 June 2008
Cellular basis of drug‐induced torsades de pointes
Authors: Roden D M
Published: June 2008

Striking QT prolongation and the morphologically distinctive ventricular tachycardia torsades de pointes can occur in up to 5% of patients treated with certain antiarrhythmic drugs. This adverse drug reaction also occurs, albeit far less frequently, during therapy with a range of drugs not used for cardiovascular indications; examples include certain antibiotics, antipsychotics and antihistamines. The common mechanism for drug‐induced torsades de pointes is inhibition of a specific repolarizing potassium current, IKr. The key question facing clinicians, regulators and those who develop drugs is why torsades de pointes only occurs in some patients exposed to IKrblock. This paper reviews the clinical, cellular, molecular and genetic features of the arrhythmia that may provide an answer to this question and proposes future studies in this area.

British Journal of Pharmacology(2008)154, 1502–1507; doi:fn1; published online 16 June 2008
Sensitive and reliable proarrhythmiain vivoanimal models for predicting drug‐induced torsades de pointes in patients with remodelled hearts
Authors: Sugiyama A
Published: June 2008

As an increasing number of non‐cardiac drugs have been reported to cause QT interval prolongation and torsades de pointes (TdP), we extensively studied the utility of atrioventricular (AV) block animals as a model to predict their torsadogenic action in human. The present review highlights suchin vivoproarrhythmia models. In the case of the canine model, test substances were administered p.o. at conscious state >4 weeks after the induction of AV block, with subsequent Holter ECG monitoring to evaluate drug effects. Control AV block dogs (no pharmacological treatment) survive for several years without TdP attack. For pharmacologically treated dogs, drugs were identified as high, low or no risk. High‐risk drugs induced TdP at 1–3 times the therapeutic dose. Low‐risk drugs did not induce TdP at this dose range, but induced it at higher doses. No‐risk drugs never induced TdP at any dose tested. Electrophysiological, anatomical histological and biochemical adaptations against persistent bradycardia‐induced chronic heart failure were observed in AV block dogs. Recently, we have developed another highly sensitive proarrhythmia model using a chronic AV block cynomolgus monkey, which possesses essentially the same pathophysiological adaptations and drug responses as those demonstrated in the canine model. As a common remodelling process leading to a diminished repolarization reserve may present in patients who experience drug‐induced TdP and in the AV block animals, thein vivoproarrhythmia models described in this review may be useful for predicting the risk of pharmacologically induced TdP in humans.

British Journal of Pharmacology(2008)154, 1528–1537; doi:fn1; published online 16 June 2008
Emodin is a novel alkaline nuclease inhibitor that suppresses herpes simplex virus type 1 yields in cell cultures
Authors: Hsiang C‐Y , Ho T‐Y
Published: June 2008

Background and purpose:

Most antiviral therapies directed against herpes simplex virus (HSV) infections are limited to a small group of nucleoside analogues that target the viral polymerase. Extensive clinical use of these drugs has led to the emergence of resistant viral strains, mainly in immunocompromised patients. This highlights the need for the development of new anti‐herpesviral drugs with novel targets. Herein the effects of a plant anthraquinone, emodin, on the HSV‐1 alkaline nuclease activity and virus yields were investigated.

Experimental approach:

HSV‐1 alkaline nuclease activity was examined by nuclease activity assay. Inhibition of virus yields was measured by plaque reduction assay and immunohistochemical staining. Interaction between emodin and alkaline nuclease was analysed by docking technology.

Key results:

Emodin specifically inhibited the nuclease activity of HSV‐1 UL12 alkaline nuclease in a biochemical assay. Plaque reduction assay revealed that emodin reduced the plaque formation with an EC50 of 21.5±4.4 μM. Immunohistochemical staining using the anti‐nucleocapsid protein antibody demonstrated that emodin induced the accumulation of viral nucleocapsids in the nucleus in a dose‐dependent manner. Docking analysis further suggested that the inhibitory effect of emodin on the UL12 activity may result from the interaction between emodin and critical catalytic amino acid residues of UL12.

Conclusions and implications:

Our findings suggest that emodin is a potent anti‐HSV agent that inhibits the yields of HSV‐1 via the suppression of a novel target, UL12.

British Journal of Pharmacology (2008) 155, 227–235; doi:10.1038/bjp.2008.242; published online 16 June 2008
Prediction of clinical response based on pharmacokinetic/pharmacodynamic models of 5‐hydroxytryptamine reuptake inhibitors in mice
Authors: Kreilgaard M , Smith D G , Brennum L T , Sánchez C
Published: June 2008

Background and purpose:

Bridging the gap between preclinical research and clinical trials is vital for drug development. Predicting clinically relevant steady‐state drug concentrations (Css) in serum from preclinical animal models may facilitate this transition. Here we used a pharmacokinetic/pharmacodynamic (PK/PD) modelling approach to evaluate the predictive validity of 5‐hydroxytryptamine (5‐HT; serotonin) transporter (SERT) occupancy and 5‐hydroxytryptophan (5‐HTP)‐potentiated behavioral syndrome induced by 5‐HT reuptake inhibitor (SRI) antidepressants in mice.

Experimental approach:

Serum and whole brain drug concentrations, cortical SERT occupancy and 5‐HTP‐potentiated behavioral syndrome were measured over 6 h after a single subcutaneous injection of escitalopram, paroxetine or sertraline. [3H]2‐(2‐dimethylaminomethylphenylsulphanyl)‐5‐methyl‐phenylamine ([3H]MADAM) was used to assess SERT occupancy. For PK/PD modelling, an effect‐compartment model was applied to collapse the hysteresis and predict the steady‐state relationship between drug exposure and PD response.

Key results:

The predicted Css for escitalopram, paroxetine and sertraline at 80% SERT occupancy in mice are 18 ng mL−1, 18 ng mL−1 and 24 ng mL−1, respectively, with corresponding responses in the 5‐HTP behavioral model being between 20–40% of the maximum.

Conclusions and implications:

Therapeutically effective SERT occupancy for SRIs in depressed patients is approximately 80%, and the corresponding plasma Css are 6–21 ng mL−1, 21‐95 ng mL−1 and 20–48 ng mL−1 for escitalopram, paroxetine and sertraline, respectively. Thus, PK/PD modelling using SERT occupancy and 5‐HTP‐potentiated behavioral syndrome as response markers in mice may be a useful tool to predict clinically relevant plasma Css values.

British Journal of Pharmacology (2008) 155, 276–284; doi:10.1038/bjp.2008.243; published online 16 June 2008
Metabolic responses to BRL37344 and clenbuterol in soleus muscle and C2C12 cells via different atypical pharmacologies and β2‐adrenoceptor mechanisms
Authors: Ngala R A , O'Dowd J , Wang S J , Agarwal A , Stocker C , Cawthorne M A , Arch J R S
Published: June 2008

Background and purpose:

Picomolar concentrations of the β3‐adrenoceptor agonist BRL37344 stimulate 2‐deoxyglucose uptake in soleus muscle via undefined receptors. Higher concentrations alter uptake, apparently via β2‐adrenoceptors. Effects of BRL37344 and β2‐adrenoceptor agonists are compared.

Experimental approach:

Mouse soleus muscles were incubated with 2‐deoxy[1‐14C]‐glucose, [1‐14C]‐palmitate or [2‐14C]‐pyruvate, and BRL37344, β2‐adrenoceptor agonists and selective β‐adrenoceptor antagonists. Formation of 2‐deoxy[1‐14C]‐glucose‐6‐phosphate or14CO2was measured. 2‐Deoxy[1‐14C]‐glucose uptake and β‐adrenoceptor mRNA were measured in C2C12 cells.

Key results:

10 pMBRL37344, 10 pMclenbuterol and 100 pMsalbutamol stimulated 2‐deoxyglucose uptake in soleus muscle by 33–54%. The effect of BRL37344 was prevented by 1 μMatenolol but not by 300 nMCGP20712A or IC3118551, or 1 μMSR59230A; that of clenbuterol was prevented by ICI118551 but not atenolol. 10 nMBRL37344 st4mulated 2‐deoxyglucose uptake, whereas 100 nMclenbuterol and salbutamol inhibited uptake. These effects were blocked by ICI118551. Similar results were obtained in C2C12 cells, in which only β2‐adrenoceptor mRNA could be detected by RT‐PCR. 10 nMBRL37344 and 10 pMclenbuterol stimulated muscle palmitate oxidation. In the presence of palmitate, BRL37344 no longer stimulated 2‐deoxyglucose uptake and the effect of clenbuterol was not significant.

Conclusions and implications:

Stimulation of glucose uptake by 10 pMBRL37344 and clenbuterol involves different atypical pharmacologies. Nanomolar concentrations of BRL37344 and clenbuterol, probably acting via β2‐adrenoceptors, have opposite effects on glucose uptake. The agonists preferentially stimulate fat rather than carbohydrate oxidation, but stimulation of endogenous fat oxidation cannot explain why 100 nMclenbuterol inhibited 2‐deoxyglucose uptake.

British Journal of Pharmacology(2008)155, 395–406; doi:fn1; published online 16 June 2008
The α1A‐adrenoceptor gene is required for the α1L‐adrenoceptor‐mediated response in isolated preparations of the mouse prostate
Authors: Gray K T , Short J L , Ventura S
Published: June 2008

Background and purpose:

This study investigated whether deletion of the α1A‐adrenoceptor gene influences contractile responses of mouse prostate to noradrenaline. Responses of mouse prostate to noradrenaline are known to be mediated by α1L‐adrenoceptors, which are thought to be a functional phenotype of α1A‐adrenoceptor.

Experimental approach:

Prostate tissues from α1A‐adrenoceptor knockout mice which were homozygous (α1A−/−) and heterozygous (α1A+/−) for the disrupted α1A‐adrenoceptor gene, as well as wild‐type (α1A+/+) littermates were mounted in glass‐isolated organ baths. Electrical field stimulation of nerves and exogenous application of noradrenaline were used to investigate the effects of α1A‐adrenoceptor disruption on prostate contractility.

Key results:

Frequency–response curves to electrical field stimulation (0.5 ms pulse duration, 60 V, 0.1–20 Hz) yielded frequency‐dependent contractions. At frequencies of 10 and 20 Hz, prostates from α1A−/− mice elicited an approximately 30% decreased response compared with prostates from α1A+/+ mice. Prazosin (0.3 μM) attenuated responses to electrical field stimulation in prostates from α1A+/+ and α1A+/− mice but not from α1A−/− mice. Increasing concentrations of exogenously administered noradrenaline (10 nM–1 mM) produced mean concentration–response curves in prostates from α1A+/+ and α1A+/− mice, which were not different. Maximum responses to noradrenaline were decreased by approximately 80% in prostates from α1A−/− mice compared with α1A+/+ mice. Prazosin attenuated responses to noradrenaline in all genotypes.

Conclusions and implications:

α1L‐Adrenoceptor‐mediated responses in mouse prostate are abolished in α1A−/− mice, demonstrating that the α1A‐adrenoceptor gene is essential to the manifestation of the prostatic α1L‐adrenoceptor phenotype. This implies that α1L‐adrenoceptors are indeed a functional phenotype of α1A‐adrenoceptor.

British Journal of Pharmacology(2008)155, 103–109; doi:fn1; published online 16 June 2008