bluuebunny/crossref_metadata_2025 huggingface dataset:
Viscous flows in a muddy seabed induced by a solitary wave
Authors: PARK YONG SUNG , LIU PHILIP L.-F. , CLARK STEPHEN J.
Published: February 2008

Liu & Chan (J. Fluid Mech.vol. 579, 2007, p. 467, hereinafter referred to as LC) derived analytical solutions for the interactions between shallow water waves and a viscous fluid seabed. In this paper we present a set of new experimental data on the solitary-wave-induced flows in a viscous muddy seabed so as to validate LC's theory and the approximations employed. In the experiments a clear silicone fluid was used as the viscous mud and particle image velocimetry was employed to measure the velocity field inside the viscous mud. The shear stress along the bottom of the mud bed and the displacement of the water--mud interface were also deduced from data. Experimental results showed excellent agreement with the theoretical solutions. Additional analyses were performed to show that the ratio of the muddy seabed thickness to the corresponding bottom boundary-layer thickness,$\dbar$, plays an important role in characterizing mud flow regimes. When$\dbar\,{\leq}\,1$, the vertical profile of the horizontal velocity in the mud bed can be parameterized as a parabola. On the other hand, when$\dbar\,{\gg}\,1$, the velocity profile appears as a plug flow above a thin viscous layer. When$ \dbar\,{\sim}\,O(1)$, the flow patterns are more complex than the other two regimes and flow reversal can occur inside the viscous mud bed.
Direct numerical simulation of vortex ring evolution from the laminar to the early turbulent regime
Authors: ARCHER P. J. , THOMAS T. G. , COLEMAN G. N.
Published: February 2008

Direct numerical simulation is used to study the temporal development of single vortex rings at various Reynolds numbers and core thicknesses. Qualitative differences between the evolution of thin- and thick-core rings are observed leading to a correction factor to the classical equation for the ring translational velocity. We compare the obtained linear modal growth rates with previous work, highlighting the role of the wake in triply periodic numerical simulations. The transition from a laminar to a turbulent ring is marked by the rearrangement of the outer core vorticity into a clearly defined secondary structure. The onset of the fully turbulent state is associated with shedding of the structure in a series of hairpin vortices. A Lagrangian particle analysis was performed to determine the ring entrainment and detrainment properties and to investigate the possibility of an axial flow being generated around the circumference of the core region prior to the onset of turbulence.
Experimental study of higher-order moments in shear-driven boundary layers with rotation
Authors: FERRERO E. , GENOVESE R. , LONGHETTO A. , MANFRIN M. , MORTARINI L.
Published: February 2008

The results of laboratory wall turbulence experiments on a shear-driven rotating boundary layer are presented. The experiments were carried out in the Turin University Laboratory rotating water tank. The flow was generated by changing the rotation speed of the platform and measured by means of particle image velocimetry. In order to analyse the influence of the rotation and of surface roughness, different cases were examined. Several rotation periods were considered. The measurements were performed both over a smooth surface and over a rough-to-smooth transition. Mean flows and the higher-order moments of the velocity probability density function are shown and discussed together with a comparison of the different experimental cases, theory and large-eddy simulations.
A Lagrangian investigation of the small-scale features of turbulent entrainment through particle tracking and direct numerical simulation
Authors: HOLZNER MARKUS , LIBERZON A. , NIKITIN N. , LÜTHI B. , KINZELBACH W. , TSINOBER A.
Published: February 2008

We report an analysis of small-scale enstrophy ω2and rate of strains2dynamics in the proximity of the turbulent/non-turbulent interface in a flow without strong mean shear. The techniques used are three-dimensional particle tracking (3D-PTV), allowing the field of velocity derivatives to be measured and followed in a Lagrangian manner, and direct numerical simulations (DNS). In both experiment and simulation the Taylor-microscale Reynolds number isReλ= 50. The results are based on the Lagrangian viewpoint with the main focus on flow particle tracers crossing the turbulent/non-turbulent interface. This approach allowed a direct investigation of the key physical processes underlying the entrainment phenomenon and revealed the role of small-scale non-local, inviscid and viscous processes. We found that the entrainment mechanism is initiated by self-amplification ofs2through the combined effect of strain production and pressure--strain interaction. This process is followed by a sharp change of ω2induced mostly by production due to viscous effects. The influence of inviscid production is initially small but gradually increasing, whereas viscous production changes abruptly towards the destruction of ω2. Finally, shortly after the crossing of the turbulent/non-turbulent interface, production and dissipation of both enstrophy and strain reach a balance. The characteristic time scale of the described processes is the Kolmogorov time scale, τη. Locally, the characteristic velocity of the fluid relative to the turbulent/non-turbulent interface is the Kolmogorov velocity,uη.
Experimental investigation of homogeneity, isotropy, and circulation of the velocity field in buoyancy-driven turbulence
Authors: ZHOU QUAN , SUN CHAO , XIA KE-QING
Published: February 2008

We present direct multipoint velocity measurements of the two-dimensional velocity field in the central region of turbulent Rayleigh–Bénard convection. The local homogeneity and isotropy of the velocity field are tested using a number of criteria and are found to hold to an excellent degree. The properties of velocity circulation Γrare also studied. The results show that the circulation appears to be more effective in capturing the effect of local anisotropy than the velocity field itself. The distribution of Γris found to depend on the scaler, reflecting strong intermittency. It is further found that the velocity circulation has the same anomalous scaling exponents as the longitudinal and transverse structure functions for low-order moments (p≲5), whereas, for high-order moments (p≳5), the anomalous scaling exponents for circulation are found to be systematically smaller than the scaling exponents of the longitudinal and transverse structure functions.
Comparative real-time PCR and enzyme analysis of selected gender-associated molecules inSchistosoma japonicum
Authors: MOERTEL L. , GOBERT G. N. , McMANUS D. P.
Published: February 2008

Schistosomes are complex parasitic helminths with discrete life-cycle stages, adapted for survival in their mammalian and snail hosts and the external aquatic environment. Recently, we described the fabrication and use of a microarray to investigate gender-specific transcription inSchistosoma japonicum. To address transcriptional differences, 8 gender-associated gene transcripts identified previously by the microarray analysis were selected for further study. First, differential transcription patterns were investigated in 4 developmental stages using real-time PCR. Subsequently, we undertook functional analysis of a subset of 4 transcripts encoding metabolic enzymes, so as to correlate gender-associated transcript levels with enzyme activity in protein extracts from adult worms. The 8 characterized molecules serve as a basis for further investigation of differential gene expression during the schistosome life-cycle and for studying the sexual dimorphism of adult worms. Continual refinement and annotation of the microarray used in the current study should support future work on these aspects.
Dissociative responses to conscious and non-conscious fear impact underlying brain function in post-traumatic stress disorder
Authors: Felmingham K. , Kemp A. H. , Williams L. , Falconer E. , Olivieri G. , Peduto A. , Bryant R.
Published: February 2008

Background

Dissociative reactions in post-traumatic stress disorder (PTSD) have been regarded as strategic responses that limit arousal. Neuroimaging studies suggest distinct prefrontal responses in individuals displaying dissociative and hyperarousal responses to threat in PTSD. Increased prefrontal activity may reflect enhanced regulation of limbic arousal networks in dissociation. If dissociation is a higher-order regulatory response to threat, there may be differential responses to conscious and automatic processing of threat stimuli. This study addresses this question by examining the impact of dissociation on fear processing at different levels of awareness.

Method

Functional magnetic resonance imaging (fMRI) with a 1.5-T scanner was used to examine activation to fearful (versusneutral) facial expressions during consciously attended and non-conscious (using backward masking) conditions in 23 individuals with PTSD. Activation in 11 individuals displaying non-dissociative reactions was compared to activation in 12 displaying dissociative reactions to consciously and non-consciously perceived fear stimuli.

Results

Dissociative PTSD was associated with enhanced activation in the ventral prefrontal cortex for conscious fear, and in the bilateral amygdala, insula and left thalamus for non-conscious fear compared to non-dissociative PTSD. Comparatively reduced activation in the dissociative group was apparent in dorsomedial prefrontal regions for conscious fear faces.

Conclusions

These findings confirm our hypotheses of enhanced prefrontal activity to conscious fear and enhanced activity in limbic networks to non-conscious fear in dissociative PTSD. This supports the theory that dissociation is a regulatory strategy invoked to cope with extreme arousal in PTSD, but this strategy appears to function only during conscious processing of threat.
The development of fears from early adolesence to young adulthood: a multivariate study
Authors: Kendler K. S. , Gardner C. O. , Annas P. , Lichtenstein P.
Published: February 2008

Background

Common fears change over development. Genetic and environmental risk factors for fears are partly shared across fears and partly fear-specific. The nature of the changes in common and fear-specific genetic and environmental risk factors over time is unknown.

Method

Self-reported fears were obtained at ages 13–14, 16–17 and 19–20 from 2404 twins in the Swedish Twin Study of Child and Adolescent Development. A multivariate longitudinal twin analysis was conducted with Mx.

Results

Eighteen individual items formed four fear factors: animal, blood-injury, situational, and social. The best-fit model had no quantitative or qualitative sex effects or shared environmental effects, but included a strong common factor with a stable cross-time structure with highest loadings on situational and lowest loadings on social fears. New common and fear-specific genetic risk factors emerged over development. With increasing age, genetic effects declined in overall importance and became more fear-specific. Cross-time continuity in specific genetic effects was highest for animal and lowest for social fears. Social fears had a ‘burst’ of specific genetic effects in late adolescence. Individual-specific environmental factors impacted both on the general fear factor and on specific fears. Compared to genetic effects, the impact of the unique environment was more time-specific.

Conclusions

Genetic and environmental risk factors for individual fears are partly mediated through a common fear factor and are partly fear-specific in their effect. The developmental pattern of these risk factors is complex and dynamic with new common and specific genetic effects arising in late adolescence and early adulthood.
Life events, anxious depression and personality: a prospective and genetic study
Authors: Middeldorp C. M. , Cath D. C. , Beem A. L. , Willemsen G. , Boomsma D. I.
Published: February 2008

Background

The association between life events and anxious depression might be due to causality or to gene–environment correlation. We examined unidirectional and reciprocal causality and a gene–environment correlation model, in which genes that influence the vulnerability for anxious depression also increase the risk of exposure to life events. The effect of genes that influence environmental exposure might be mediated through personality and we therefore also examined the association between life events and personality (neuroticism and extraversion).

Method

Information on life events, anxious depression, neuroticism and extraversion was collected in 5782 monozygotic (MZ) and dizygotic (DZ) twins who participated in a longitudinal survey study of the Netherlands Twin Register. To examine causality, data were analysed longitudinally. To examine gene–environment correlation, the co-twin control method was used.

Results

Anxious depression and, to a lesser extent, neuroticism scores increased after exposure to life events. Anxious depression and neuroticism also predicted the experience of life events. Prospectively, extraversion was not associated with life events. Anxious depression, neuroticism and extraversion scores did not differ between the non-exposed subjects of MZ and DZ twin pairs and unrelated subjects discordant for life events.

Conclusions

Our findings suggest that reciprocal causation explains the relationship between life events and anxious depression and between life events and neuroticism. Extraversion is not related to life events. No evidence was found for gene–environment correlation, i.e. the genes that influence anxious depression, neuroticism or extraversion do not overlap with the genes that increase the risk of exposure to life events.
Analysis of rubella antibody distribution from newborn dried blood spots using finite mixture models
Authors: HARDELID P. , WILLIAMS D. , DEZATEUX C. , TOOKEY P. A. , PECKHAM C. S. , CUBITT W. D. , CORTINA-BORJA M.
Published: February 2008

Eluted dried blood spot specimens from newborn screening, collected in 2004 in North Thames and anonymously linked to birth registration data, were tested for maternally acquired rubella IgG antibody as a proxy for maternal antibody concentration using an enzyme-linked immunosorbent assay. Finite mixture regression models were fitted to the antibody concentrations from 1964 specimens. The Bayesian Information Criterion (BIC) was used as a model selection criterion to avoid over-fitting the number of mixture model components. This allowed investigation of the independent effect of maternal age and maternal country of birth on rubella antibody concentration without dichotomizing the outcome variable using cut-off values set a priori. Mixture models are a highly useful method of analysis in seroprevalence studies of vaccine-preventable infections in which preset cut-off values may overestimate the size of the seronegative population.
Cultural Memories of the Expulsion of the Moriscos
Authors: González García José M.
Published: February 2008

Violins are weeping over the Arabs leaving al-Andalus,

Violins are weeping over lost time which will never come back

(Palestinian poet Mahmud Darwish1)

In 2009 it will have been 400 years since Philip III expelled the Moriscos from Spain. It is therefore time to consider what remains of this tragedy in present-day Spanish collective memory. As opposed to the history as written by the victors it is necessary to also listen to the voice of the descendants of the victims, recovering their own historical memory. As a symbol of the reparation of an historical injustice the present-day Spanish state may grant the descendants of the expelled Moriscos the right to Spanish citizenship, as has already happened with the descendants of the Sephardim or Spanish Jews. In this article I consider four forms of memory of the expulsion of the Moriscos, embodied respectively in History, Literature, Art and Popular Culture. In the section on History, I analyze the works of Gregorio Marañón and Henry Kamen. Literary memory will be represented by the figure of the Morisco Ricote in Part II of Cervantes’ Quixote. For Art, I will look at a series of paintings commissioned by Philip III and at a painting competition held in Madrid under Philip IV. Popular culture is represented by the celebrations of ‘moros y cristianos,’ or ‘Moors and Christians,’ an old tradition that is still alive.
‘Golden Age’ Poetry in Contemporary Israeli and Palestinian Poetry
Authors: Ben-Porat Ziva
Published: February 2008

This article is a small part of a research project dealing with the presence of Hebrew poetry from al-Andalus in Israeli culture in general and in Israeli poetry in particular. In spite of its indisputably canonic status and 800-year history as a central model for the writing of poetry, this magnificent corpus is quite unknown to today’s readers, and its genres are obsolete. It is, as I shall explain, a ‘dinosaur-like’ canonic entity. The article contains some explanatory references to the historical trajectory of the poetry in question, from a central and active position to a marginal and passive presence – dealing with both the particular beneficial conditions in al-Andalus and current internal and external political situations. However, the paper is not about literary history or cultural politics. Rather, it focuses on the ways ‘dinosaur-like’ canonic status is revealed in the writing of contemporary poetry and in its readings. I begin with a short introduction concerned both with the poetry of al-Andalus and with the cognitive and inter-textual aspects related to the ‘dinosaur-like’ existence of texts and models. Owing to lack of space, I then deal with only three of the many characteristic features of this phenomenon: cognitive accessibility (illustrated by two readings of a Palestinian poem by Sami al-Kilani), manifested distancing (illustrated by Amnon Shamosh’s poem that converses with Yehuda Halevi), and modes of alluding (illustrated by a poem of Yehuda Amichai).
Grain legume–cereal intercropping: The practical application of diversity, competition and facilitation in arable and organic cropping systems
Authors: Hauggaard-Nielsen Henrik , Jørnsgaard Bjarne , Kinane Julia , Jensen Erik Steen
Published: February 2008

Intercropping is the simultaneous cultivation of more than one crop species on the same piece of land and is regarded as the practical application of basic ecological principles such as diversity, competition and facilitation. Field experiments were carried out on a sandy loam soil and a sandy soil in Denmark over three consecutive cropping seasons including dual grain legume (pea, faba bean and lupin)–barley intercropping as compared to the respective sole crops (SC). Yield stability of intercrops (IC) was not greater than that of grain legume SC, with the exception of the IC containing faba bean. Faba bean and lupin had lower yield stability than pea and fertilized barley. However, the different IC used environmental resources for plant growth up to 50% (LER=0.91–1.51) more effectively as compared to the respective SC, but with considerable variation over location, years and crops. The SC performance supported the interspecific interactions within the IC stand. On the sandy loam 13% greater grain yield of pea cv. Agadir (520 g m−2) was observed as compared to cv. Bohatyr. Faba bean and lupin yielded similarly (340 g m−2) in the sandy loam soil, with decreasing yields on the sandy soil (320–270 g m−2). Nitrogen fixation was very constant in grain legume SC over species and location, varying from 13.2 to 15.8 g N m−2, being lowest in peas and highest in faba bean and lupin. The intercropped grain legumes increased the proportion of plant N derived from N2-fixation by on average 10–15% compared to the corresponding SC. However, especially lupin was suppressed when intercropping, with a reduced N2-fixation from 15 to 5–6 g N m−2. The IC were particularly effective at suppressing weeds, capturing a greater share of available resources than SC. Weed infestation in the different crops was comparable; however, it tended to be the highest in sole cropped faba bean, lupin and unfertilized barley, where the application of urea to barley reduced the weed infestation by around 50%. Reduction in disease was observed in all IC systems compared to the corresponding SC, with a general disease reduction in the range of 20–40%. For one disease in particular (brown spot on lupin) disease reduction was almost 80% in the IC. Intercropping practices offer many advantages but improved understanding of the ecological mechanisms associated with planned spatial diversity, including additional benefits with associated diversity, is needed to enhance the benefits achieved.
Sediment database, Walnut Gulch Experimental Watershed, Arizona, United States
Authors: Nichols M. H. , Stone J. J. , Nearing M. A.
Published: February 2008

Improving the scientific understanding of erosion and sedimentation processes within semiarid rangeland watersheds has been a primary objective of data collection on the Walnut Gulch Experimental Watershed since its establishment in 1953. Sampling instruments and techniques are described, including the traversing slot sediment sampler, pump samplers on both V notch weirs and H flumes, and stock tank sedimentation surveys. Sediment collected at the outlets of seven small watersheds and long‐term data collected through stock tank sedimentation surveys at eight sites dating from the 1950s are described. Data are available at http://www.tucson.ars.ag.gov/dap/.
Wind‐driven latent heat flux and the intraseasonal oscillation
Authors: Araligidad Nilesh M. , Maloney Eric D.
Published: February 2008

The importance of tropical west Pacific wind‐driven latent heat flux anomalies for supporting boreal winter intraseasonal precipitation variability is analyzed during 1998–2005 using satellite and in‐situ observations. Intraseasonal (30–100 day) wind speed anomalies from QuikSCAT are significantly correlated with TRMM precipitation anomalies, with instantaneous correlations peaking near 0.7 in the regions of strongest west Pacific intraseasonal precipitation variance. Positive intraseasonal wind speed anomalies occur within regions of enhanced precipitation during intraseasonal oscillation (ISO) events, suggesting an increase in the wind‐driven component of latent heat flux then. Consistent with these results, west Pacific intraseasonal TAO buoy latent heat flux and TRMM precipitation anomalies are significantly correlated (0.5–0.6), and latent heat flux anomalies are primarily wind‐driven. Collocated evaporation anomalies are approximately 20% of intraseasonal precipitation anomalies. Intraseasonal precipitation in the west Pacific may be supported by wind‐driven surface fluxes, consistent with the modeling work of Maloney and Sobel.
A preliminary global map of the vector lunar crustal magnetic field based on Lunar Prospector magnetometer data
Authors: Richmond N. C. , Hood L. L.
Published: February 2008

Previous processing of the Lunar Prospector magnetometer (LP‐MAG) data has yielded ∼40% coverage of the Moon. Here, new mapping of the low‐altitude LP‐MAG data is reported with the goal of producing the first global vector map of the lunar crustal magnetic field. By considering all data regardless of the external plasma environment and using less restrictive editing criteria, 2360 partial and complete passes have been identified that can be used to investigate the lunar crustal magnetic anomalies. The cleanest global coverage is provided using 329 low‐altitude nightside and terminator passes. An inverse power method has been used to continue the final mapping data to constant altitude. Using the 329 optimal passes, global maps of the lunar crustal magnetic field are constructed at 30 and 40 km. Consistent with previous studies: (1) the largest concentrations of anomalies are mapped antipodal to the Crisium, Serenitatis, Imbrium, and Orientale basins and (2) isolated anomalies at Reiner Gamma, Rima Sirsalis, Descartes, and Airy are mapped. Anomalies previously unmapped by the LP‐MAG experiment include (1) isolated anomalies near the craters Abel and Hartwig, (2) weak magnetization within the Nectarian‐aged Crisium and Moscoviense basins, and (3) a relatively weak anomaly in an area dominated by crater chains associated with the formation of Nectaris. Future work with the new low‐altitude data set is discussed and will include determining whether the lunar anomalies are capable of deflecting the solar wind and investigating directions of magnetization to evaluate a possible former core dynamo.
The antiarrhythmic effect of centrally administered rilmenidine involves muscarinic receptors, protein kinase C and mitochondrial signalling pathways
Authors: Iwasaki M , Hayashi Y , Kamibayashi T , Yamatodani A , Mashimo T
Published: February 2008

Background and purpose:We have previously demonstrated that stimulation of imidazoline receptors in the CNS prevented halothane–adrenaline arrhythmias during halothane anaesthesia and that stimulation of the vagus nerve may be critical to this effect. However, details of the mechanism(s) involved are not yet available. The present study was designed to examine the role of muscarinic receptors, protein kinase C (PKC), ATP‐sensitive potassium channels (KATP) and the mitochondrial permeability transition pore (MPTP) in the antiarrhythmic effect of rilmenidine, an imidazoline receptor agonist.

Experimental approach:Rats were anaesthetized with halothane and monitored continuously for arterial blood pressure and premature ventricular contractions. The arrhythmogenic dose of adrenaline was defined as the lowest dose producing three or more premature ventricular contractions within a 15‐s period. We confirmed that centrally administered rilmenidine prevented halothane–adrenaline arrhythmias and then examined the antiarrhythmic effect of rilmenidine in the presence of atropine methylnitrate, a muscarinic receptor antagonist, calphostin C, a PKC inhibitor, HMR‐1098, a sarcolemmal KATPinhibitor, 5‐hydroxydecanoic acid, a mitochondrial KATPinhibitor or atractyloside, an MPTP opener.

Key results:The antiarrhythmic effect of rilmenidine was significantly inhibited by atropine methylnitrate, calphostin C, 5‐hydroxydecanoic acid and atractyloside, but the effects of HMR‐1098 in our model were not clear.

Conclusions and implications:The present results suggest that muscarinic receptors, PKC, mitochondrial KATPchannels and MPTP may be crucial components of the mechanism involved in the antiarrhythmic effect of rilmenidine given into the CNS.

British Journal of Pharmacology(2008)153, 1623–1630; doi:10.1038/bjp.2008.35; published online 25 February 2008
Indomethacin promotes nitric oxide function in the ductus arteriosus in the mouse
Authors: Sodini D , Baragatti B , Barogi S , Laubach V E , Coceani F
Published: February 2008

Background and purpose:

Prenatal patency of ductus arteriosus is maintained by prostaglandin (PG) E2in concert with nitric oxide (NO) and carbon monoxide (CO). Accordingly, we have previously found that NO activity increases upon deletion of either COX. Here, we have examined whether COX inhibition by indomethacin mimics COX deletion in promoting NO.

Experimental approach:

Experiments were performedin vitroandin vivowith wild‐type (WT) and eNOS−/−, near‐term mouse foetuses. Indomethacin was given p.o. to the mother as single (acute treatment) or repeated (daily for 3 days; chronic treatment) doses within a therapeutic range (2 mg kg−1).

Key results:

Indomethacin promoted eNOS mRNA expression in the WT ductus. Coincidentally, the drug enhanced the contraction of the isolated ductus to the NOS inhibitor,NG‐nitro‐L‐arginine methyl ester, and its effect augmented with the length of treatment. No such enhancement was seen with the eNOS−/− ductus. Chronic indomethacin also increased, albeit marginally, the contraction of the WT ductus to the CO synthesis inhibitor, zinc protoporphyrin. Whether given acutely or chronically, indomethacin induced a little narrowing of the ductus antenatally and had no effect on postnatal closure of the vessel.

Conclusions and implications:

We conclude that activation of NO and, to a much lesser degree, CO mechanisms is an integral part of the indomethacin effect on the ductus. This relaxing influence may oppose the contraction from PGE2suppression and could explain the failures of indomethacin therapy in premature infants with persistent duct.

British Journal of Pharmacology(2008)153, 1631–1640; doi:10.1038/bjp.2008.36; published online 25 February 2008
A nitric oxide/Ca2+/calmodulin/ERK1/2 mitogen‐activated protein kinase pathway is involved in the mitogenic effect of IL‐1β in human astrocytoma cells
Authors: Meini A , Sticozzi C , Massai L , Palmi M
Published: February 2008

Background and purpose:

Evidence is accumulating to support a role for interleukin‐1β (IL‐1β) in astrocyte proliferation. However, the mechanism by which this cytokine modulates this process is not fully elucidated.

Experimental approach:

In this study we used human astrocytoma U‐373MG cells to investigate the role of nitric oxide (NO), intracellular Ca2+ concentration ([Ca2+]i), and extracellular signal‐regulated protein kinase (ERK) in the signalling pathway mediating IL‐1β‐induced astrocyte proliferation.

Key results:

Low IL‐1β concentrations induced dose‐dependent ERK activation which paralleled upregulation of cell division, whereas higher concentrations gradually reversed both these responses by promoting apoptosis. Pretreatment with the nonspecific NOS inhibitor, N‐ω‐nitro‐l‐arginine methyl ester (L‐NAME) or the selective iNOS inhibitor, N‐[[3‐(aminomethyl)phenyl]methyl]‐ethanimidamide dihydrochloride (1400W), antagonized ERK activation and cell proliferation induced by IL‐1β. Inhibition of cGMP formation by the guanylate cyclase inhibitor, 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ), partially inhibited ERK activation and cell division. Functionally blocking Ca2+ release from endoplasmic reticulum with ryanodine or 2‐aminoethoxydiphenylborane (2‐APB), inhibiting calmodulin (CaM) activity with N‐(6‐aminohexyl)‐5‐chloro‐1‐naphthalenesulphonamide hydrochloride (W7) or MAPK kinase activity with 1,4‐diamino‐2,3‐dicyano‐1,4‐bis[2‐aminophenylthiol]butadiene (U0126) downregulated IL‐1β‐induced ERK activation as well as cell proliferation. The cytokine induced a transient and time‐dependent increase in intracellular NO levels which preceded elevation in [Ca2+]i.

Conclusions and implications:

These data identified the NO/Ca2+/CaM/ERK signalling pathway as a novel mechanism mediating the mitogenic effect of IL‐1β in human astrocytes. As astrocyte proliferation is a hallmark of reactive astrogliosis, our results reveal a new potential target for therapeutic intervention in neuroinflammatory disorders.

British Journal of Pharmacology (2008) 153, 1706–1717; doi:10.1038/bjp.2008.40; published online 25 February 2008
A physiological role for endocannabinoid‐derived products of cyclooxygenase‐2‐mediated oxidative metabolism
Authors: Guindon J , Hohmann A G
Published: February 2008

The endocannabinoid lipid 2‐arachidonoylglycerol (2‐AG) is deactivated by intracellular hydrolysis catalyzed by monoacylglycerol lipase. 2‐AG also serves as a substrate for oxidative metabolism catalyzed by cyclooxygenase 2 (COX‐2). However, products of COX‐2‐mediated metabolism of endocannabinoids have not been identifiedin vivo. Hu and colleagues in this issue of theBJPdemonstrate that COX‐2 converts 2‐AG into a biologically active, pro‐nociceptive compound, prostaglandin E2glycerol ester (PGE2‐G). PGE2‐G produces hyperalgesiain vivoand activates a rapidly acting transcription factor, nuclear factor kappa‐Bin vitro. These biological actions may be attributed to a unique receptor. This report of pro‐nociceptive actions of an endogenous COX‐2 metabolite of 2‐AG that are largely opposite to known anti‐nociceptive and anti‐inflammatory actions of endocannabinoids has physiological relevance. These discoveries place renewed emphasis on the importance of understanding the highly interactive nature of lipid signalling pathways in the nervous system and the physiological roles of these lipid mediators in controlling homeostasis.

British Journal of Pharmacology(2008)153, 1341–1343; doi:10.1038/bjp.2008.41; published online 25 February 2008
Structural requirements for the cytoprotective actions of mono‐unsaturated fatty acids in the pancreatic β‐cell line, BRIN‐BD11
Authors: Dhayal S , Welters H J , Morgan N G
Published: February 2008

Background and purpose: Exposure of pancreatic β‐cells to long‐chain free fatty acids leads to differential responses according to the chain length and degree of unsaturation. In particular, long‐chain saturated molecules such as palmitate (C16:0) cause apoptosis, whereas equivalent mono‐unsaturated species (for example, palmitoleate (C16:1)) are not overtly toxic. Moreover, mono‐unsaturates exert a powerful cytoprotective response against a range of proapoptotic stimuli. However, the structural requirements that determine cytoprotection have not been determined and form the basis of the present study.

Experimental approach: BRIN‐BD11 and INS‐1 β‐cells were exposed either to the saturated fatty acid palmitate, or to serum withdrawal, to mediate cytotoxicity. The protective effects of a wide range of mono‐unsaturated fatty acid derivatives were tested in cytotoxicity assays. Effector caspase activity was also measured and correlated with viability.

Key results: The cytotoxic actions of palmitate were inhibited dose‐dependently by long‐chain mono‐unsaturated fatty acids with a defined potency order C18:1>C16:1≫C14:1. The configuration of the double bond was also important with cis forms being more potent than trans forms. Alkylated mono‐unsaturated fatty‐acid derivates were also cytoprotective, although their efficacy declined as the alkyl chain length increased. Cytoprotection was achieved rapidly on addition of mono‐unsaturates and correlated with a rapid and dramatic inhibition of caspase‐3/7 activity in palmitate‐treated cells.

Conclusions and implications: The data reveal the structural requirements that dictate the cytoprotective actions of mono‐unsaturated fatty acids in pancreatic β‐cells. Metabolic activation is not required and the data point at the potential involvement of a fatty acid receptor in mediating cytoprotection.

British Journal of Pharmacology (2008) 153, 1718–1727; doi:10.1038/bjp.2008.43; published online 25 February 2008
Role of CCK and potential utility of CCK1 receptor antagonism in the treatment of pancreatitis induced by biliary tract obstruction
Authors: Barrett T D , Yan W , Freedman J M , Lagaud G J , Breitenbucher J G , Shankley N P
Published: February 2008

Background and purpose: Cholecystokinin (CCK) stimulates the release of amylase and lipase from the normal pancreas. However, it is not clear to what extent this occurs in the early stages of pancreatitis induced by biliary tract obstruction in the rat and whether CCK initiates an inflammatory cascade in this condition.

Experimental approach: Selective CCK1 receptor antagonists, JNJ‐17156516 ((S)‐(3‐[5‐(3,4‐dichloro‐phenyl)‐1‐(4‐methoxy‐phenyl)‐1H‐pyrazol‐3‐yl]‐2‐m‐tolyl‐propionic acid) and dexloxiglumide, were used to assess the response of plasma amylase and lipase to a CCK analogue, CCK8S, in normal rats and in rats with bile duct ligation.

Key results: Both antagonists suppressed CCK8S‐induced elevation of plasma amylase activity in normal rats. JNJ‐17156516 was more potent than dexloxiglumide (ED50=8.2 vs >30 μmol kg−1 p.o.) and produced a longer lived inhibition (6 vs 2 h). Plasma amylase and lipase activity were elevated in parallel to CCK plasma concentrations after bile duct ligation and both activities were suppressed in a dose‐dependent manner by JNJ‐17156516 and dexloxiglumide. JNJ‐17156516 was ∼5‐ to 10‐fold more potent than dexloxiglumide. Infusion of CCK8S to naïve rats to achieve levels similar to those observed after bile duct ligation (20 pM) increased plasma amylase activity and activated nuclear factor‐κB in the pancreas. These effects were prevented by pretreatment with JNJ‐17156516.

Conclusions and implications: The elevation of plasma amylase and lipase activity in the early stages of obstruction‐induced pancreatitis is largely driven by elevation of plasma CCK concentration and activation of CCK1 receptors. These data show that CCK is an initiating factor in acute pancreatitis in the rat.

British Journal of Pharmacology (2008) 153, 1650–1658; doi:10.1038/bjp.2008.44; published online 25 February 2008
Cardiovascular effects of activation of central α7 and α4β2 nAChRs: a role for vasopressin in anaesthetized rats
Authors: Moore C , Wang Y , Ramage A G
Published: February 2008

Background and purpose: Central application of nicotine causes the release of vasopressin and affects blood pressure. Involvement of the 5 neuronal nicotinic receptor groups, α2*–α7* in these effects is unknown. The availability of selective agonists for α7 (PSAB‐OFP) and α4β2 (TC‐2559) nACh receptors allowed their role to be investigated.

Experimental approach: Recordings were made of arterial blood pressure, heart rate and renal sympathetic nerve activity in anaesthetized male rats with neuromuscular blockade and artificial respiration. Effects of the agonists, PSAB‐OFP (1–10 μmol kg−1) and TC‐2559 (1–10 μmol kg−1) on these variables given intracerebroventricularly (i.c.v.) and intracisternally (i.c.) in the presence or absence of the antagonists, DhβE (10 μmol kg−1) and MLA (0.5 μmol kg−1), for the appropriate nicotinic receptor subtypes, respectively, and a V1 receptor antagonist, given i.v. or centrally, were investigated.

Key results: Both agonists given i.c.v. caused a delayed rise in blood pressure and renal nerve activity which could be blocked only with the appropriate antagonist. The agonists had an earlier onset of action when given i.c., favouring the brainstem as the major site of action. The effects of these agonists were also attenuated by the V1 receptor antagonist given i.v. and blocked when this antagonist was given centrally. Antagonists had no effect on baseline variables.

Conclusions and implications: Activation of α4β2 and α7 receptors in the brainstem is mainly responsible for the cardiovascular effects of activating these receptors, which have a similar profile of action. These actions, although independent, are mediated by the central release of vasopressin.

British Journal of Pharmacology (2008) 153, 1728–1738; doi:10.1038/bjp.2008.47; published online 25 February 2008
Highly Ca2+-selective TRPM Channels Regulate IP3-dependent Oscillatory Ca2+ Signaling in the C. elegans Intestine
Authors: Xing Juan , Yan Xiaohui , Estevez Ana , Strange Kevin
Published: February 2008

Posterior body wall muscle contraction (pBoc) in the nematode Caenorhabditis elegans occurs rhythmically every 45–50 s and mediates defecation. pBoc is controlled by inositol-1,4,5-trisphosphate (IP3)–dependent Ca2+ oscillations in the intestine. The intestinal epithelium can be studied by patch clamp electrophysiology, Ca2+ imaging, genome-wide reverse genetic analysis, forward genetics, and molecular biology and thus provides a powerful model to develop an integrated systems level understanding of a nonexcitable cell oscillatory Ca2+ signaling pathway. Intestinal cells express an outwardly rectifying Ca2+ (ORCa) current with biophysical properties resembling those of TRPM channels. Two TRPM homologues, GON-2 and GTL-1, are expressed in the intestine. Using deletion and severe loss-of-function alleles of the gtl-1 and gon-2 genes, we demonstrate here that GON-2 and GTL-1 are both required for maintaining rhythmic pBoc and intestinal Ca2+ oscillations. Loss of GTL-l and GON-2 function inhibits IORCa ∼70% and ∼90%, respectively. IORCa is undetectable in gon-2;gtl-1 double mutant cells. These results demonstrate that (a) both gon-2 and gtl-1 are required for ORCa channel function, and (b) GON-2 and GTL-1 can function independently as ion channels, but that their functions in mediating IORCa are interdependent. IORCa, IGON-2, and IGTL-1 have nearly identical biophysical properties. Importantly, all three channels are at least 60-fold more permeable to Ca2+ than Na+. Epistasis analysis suggests that GON-2 and GTL-1 function in the IP3 signaling pathway to regulate intestinal Ca2+ oscillations. We postulate that GON-2 and GTL-1 form heteromeric ORCa channels that mediate selective Ca2+ influx and function to regulate IP3 receptor activity and possibly to refill ER Ca2+ stores.
Geometry and the complexity of matrix multiplication
Authors: Landsberg J.
Published: February 2008

We survey results in algebraic complexity theory, focusing on matrix multiplication. Our goals are (i) to show how open questions in algebraic complexity theory are naturally posed as questions in geometry and representation theory, (ii) to motivate researchers to work on these questions, and (iii) to point out relations with more general problems in geometry. The key geometric objects for our study are the secant varieties of Segre varieties. We explain how these varieties are also useful for algebraic statistics, the study of phylogenetic invariants, and quantum computing.
Phytophthora infestans: the plant (and R gene) destroyer
Authors: FRY WILLIAM
Published: February 2008

Phytophthora infestans remains a problem to production agriculture. Historically there have been many controversies concerning its biology and pathogenicity, some of which remain today. Advances in molecular biology and genomics promise to reveal fascinating insight into its pathogenicity and biology. However, the plasticity of its genome as revealed in population diversity and in the abundance of putative effectors means that this oomycete remains a formidable foe.
Expression of transcription factors NF‐κB and AP‐1 in nasal polyposis
Authors: Valera F. C. P. , Queiroz R. , Scrideli C. , Tone L. G. , Anselmo‐Lima W. T.
Published: February 2008

Background
The treatment and prognosis of nasal polyposis (NP) may be influenced by transcription factors, but their expression is poorly understood.

Objective
To determine the expression of transcription factors [(nuclear factor‐κB) NF‐κB and (activator protein) AP‐1], cytokines [IL‐1β, TNF‐α and (granulocytes and macrophage colony‐stimulating factor) GM‐CSF], growth factor (b‐FGF), chemokine (eotaxin‐2) and adhesion molecule (ICAM‐1) in NP in comparison with nasal mucosa controls.

Methods
Cross‐sectional study. Twenty biopsies of nasal polyps were compared with eight middle turbinate biopsies. p65, c‐Fos, IL‐1β, TNF‐α, ICAM‐1, b‐FGF, eotaxin‐2 and GM‐CSF were analysed through RQ‐PCR, and p65 and c‐Fos were also analysed through Western blotting.

Results
NF‐κB expression was increased in patients with NP when compared with control mucosa (P<0.05), whereas AP‐1 expression did not differ significantly between groups. Expressions of IL‐1β, eotaxin‐2 and b‐FGF were also increased in patients with NP compared with controls (P<0.05).

Conclusions
The transcription factor NF‐κB is more expressed in NP than in control mucosa. This is important in NP because NF‐κB can induce the transcription of cytokines, chemokines and adhesion molecules, which play an important role in the inflammatory process. Moreover, transcription factors influence the response to corticosteroids, which are the basis of NP treatment. Transcription factor AP‐1 does not seem to have a significant role in the pathological process.
Detecting dispersal of Nuphar lutea in river corridors using microsatellite markers
Authors: FÉR TOMÁŠ , HROUDOVÁ ZDENKA
Published: February 2008

1. River corridors are well‐known for their role in plant dispersal. The buoyancy of seeds, the possibility of dispersal by vegetative fragments, and the frequency and efficiency of dispersal among different river catchments determine linear distribution patterns. Little is known about the relative importance of these factors to observed patterns of genetic variation.

2. One hundred and fifty‐six Nuphar lutea individuals from forty‐four sampling sites in the river catchments of the Cidlina River, the Mrlina River and the Labe River (Czech Republic) were studied using ten microsatellite markers. Interpretation of patterns in genetic variation allowed several conclusions about dispersal mechanisms.

3. Vegetative long‐distance dispersal is probably very limited in this species. Only one multilocus genotype was found in more than one sampling site. The distance between the sites was about 75 km.

4. To explain the distribution of Bayesian based clusters of related multilocus genotypes, both along‐river and inter‐river long‐distance dispersals have to be invoked.

5. A marginally significant tendency for higher genetic diversity in the lower part of the river Cidlina was detected. Continuous downstream dispersal of seeds by water currents could be a valid explanation.

6. Significant positive autocorrelation was found among individuals at within‐river distances of up to 25 km. Repeated dispersal of seeds over distances in the range of tens of kilometers is common.
The potential role of ERβ isoforms in the clinical management of breast cancer
Authors: Green C A , Peter M B , Speirs V , Shaaban A M
Published: February 2008

The discovery of a second oestrogen receptor, ERβ, was a subject of much interest, as this suggested a means to improve the prognostic stratification of invasive breast cancer, better predict response to endocrine therapy, develop new chemotherapeutic/chemopreventative drugs and perhaps prevent inappropriate treatment. However, this has not proved to be straightforward with the discovery of five ERβ isoforms and numerous exon deletion variants. This review sets out to identify the present state of knowledge regarding the clinicopathological role of ERβ isoforms and discusses possible reasons for conflicting results arising from recent research findings.
Down‐regulation of ATBF1 is a major inactivating mechanism in hepatocellular carcinoma
Authors: Kim C J , Song J H , Cho Y G , Cao Z , Lee Y S , Nam S W , Lee J Y , Park W S
Published: February 2008

Aims:  α‐Fetoprotein (AFP) is frequently detected in hepatocellular carcinomas (HCCs) and AT motif binding factor 1 (ATBF1) down‐regulates AFP gene expression in hepatic cells. The ATBF1 gene also inhibits cell growth and differentiation, and altered gene expression is associated with malignant transformation. The aim was to investigate the potential role of the ATBF1 gene in HCCs.

Methods and results:  Somatic mutations, allelic loss and hypermethylation of the ATBF1 gene were analysed in 76 sporadic HCCs. The level of ATBF‐1 mRNA expression was analysed using quantitative real‐time reverse transcriptase‐polymerase chain reaction. Genetic studies of the ATBF1 gene revealed absence of somatic mutation in the hotspot region and 15 (25%) of 60 informative cases showed allelic loss at the ATBF1 locus. Hypermethylation in the intron 1 region of the ATBF1 gene was detected in only one case. Interestingly, ATBF1 mRNA expression in HCCs was significantly reduced in 55 (72.4%) samples compared with the corresponding surrounding liver tissues. Reduced expression was not statistically associated with clinicopathological parameters including stage, histological grade, infective virus type, and serum α‐fetoprotein level.

Conclusions:  The ATBF1 gene may contribute to the development of HCCs via transcriptional down‐regulation of mRNA expression, but not by genetic or epigenetic alterations.
National guidelines for adult autopsy cardiac dissection and diagnosis – are they achievable? A personal view
Authors: Suvarna S K
Published: February 2008

Adult autopsy cardiac pathology has been previously a quiet backwater of ischaemic heart disease and the occasional cardiomyopathy. This has changed to an increasingly tense area, following recent genetic discoveries and some medicolegal cases. All autopsy pathologists should consider their dissection protocols and check that they are able to deliver the increasingly detailed information that clinicians, geneticists and families require. This text has suggestions about the practical realities of cardiac dissection, cardiac histology and the need for other tests alongside illustrations aimed to assist case consideration.