A functional genomics approach reveals novel quantitative trait loci associated with platelet signalling pathways

Platelet response to activation varies widely between individuals but shows interindividual consistency and strong heritability. The genetic basis of this variation has not been properly explored. We therefore systematically measured the effect on function of sequence variation in 97 candidate genes in the collagen and adenosine-diphosphate (ADP) signaling pathways. Resequencing of the genes in 48 European DNA samples nearly doubled the number of known single nucleotide polymorphisms (SNPs) and informed the selection of 1327 SNPs for genotyping in 500 healthy Northern European subjects with known platelet responses to collagen-related peptide (CRP-XL) and ADP. This identified 17 novel associations with platelet function (P < .005) accounting for approximately 46% of the variation in response. Further investigations with platelets of known genotype explored the mechanisms behind some of the associations. SNPs in PEAR1 associated with increased platelet response to CRP-XL and increased PEAR1 protein expression after platelet degranulation. The minor allele of a 3' untranslated region (UTR) SNP (rs2769668) in VAV3 was associated with higher protein expression (P = .03) and increased P-selectin exposure after ADP activation (P = .004). Furthermore the minor allele of the intronic SNP rs17786144 in ITPR1 modified Ca2+ levels after activation with ADP (P < .004). These data provide novel insights into key hubs within platelet signaling networks.

Functional genomics in zebrafish permits rapid characterization of novel platelet membrane proteins

In this study, we demonstrate the suitability of the vertebrate Danio rerio (zebrafish) for functional screening of novel platelet genes in vivo by reverse genetics. Comparative transcript analysis of platelets and their precursor cell, the megakaryocyte, together with nucleated blood cell elements, endothelial cells, and erythroblasts, identified novel platelet membrane proteins with hitherto unknown roles in thrombus formation. We determined the phenotype induced by antisense morpholino oligonucleotide (MO)–based knockdown of 5 of these genes in a laser-induced arterial thrombosis model. To validate the model, the genes for platelet glycoprotein (GP) IIb and the coagulation protein factor VIII were targeted. MO-injected fish showed normal thrombus initiation but severely impaired thrombus growth, consistent with the mouse knockout phenotypes, and concomitant knockdown of both resulted in spontaneous bleeding. Knockdown of 4 of the 5 novel platelet proteins altered arterial thrombosis, as demonstrated by modified kinetics of thrombus initiation and/or development. We identified a putative role for BAMBI and LRRC32 in promotion and DCBLD2 and ESAM in inhibition of thrombus formation. We conclude that phenotypic analysis of MO-injected zebrafish is a fast and powerful method for initial screening of novel platelet proteins for function in thrombosis.

Aqueous gels of mixtures of ionic surfactant SDS with pluronic copolymers P123 or F127

Gel diagrams based on tube inversion and oscillatory rheometry are reported for Pluronic copolymers F127 (E98P67E98) and P123 (E21P67E21) in mixtures with anionic surfactant sodium dodecyl sulfate (SDS). Total concentrations (e, SDS+copolymer) were as high as 50 wt% with mole ratios SDS/copolymer (mr) in the ranges 1-5 (F127) a lid 1-7 (PI 23). Temperatures were its high as 90 degrees C. Determination of the temperature dependences of the dynamic moduli served to confirm the gel boundaries from tube inversion and to reveal the high elastic moduli of the gels, e.g., compared at corn parable positions in the gel phase, a 50 wt% SDS/P123 wit h mr = 7 had G' three times that of a corresponding gel of P123 alone. Sin all-angle X-ray scattering (SAX S) was used to show that the structures of all the SDS/F127 gels were bee and that the structures of the SDS/P123 gels with mr = I were either fcc(c = 30 wt%) or hex (c = 40 wt%). Assignment of structures to SDS/P123 gels with values of mr in the range 3-7 was more difficult, as high-order scattering peaks Could be very weak, and at the higher values of c and mr, the SAXS peaks included multiple reflections.

Choices, chance and change: luck egalitarianism over time

The family of theories dubbed ‘luck egalitarianism’ represent an attempt to infuse egalitarian thinking with a concern for personal responsibility, arguing that inequalities are just when they result from, or the extent to which they result from, choice, but are unjust when they result from, or the extent to which they result from, luck. In this essay I argue that luck egalitarians should sometimes seek to limit inequalities, even when they have a fully choice-based pedigree (i.e., result only from the choices of agents). I grant that the broad approach is correct but argue that the temporal standpoint from which we judge whether the person can be held responsible, or the extent to which they can be held responsible, should be radically altered. Instead of asking, as Standard (or Static) Luck Egalitarianism seems to, whether or not, or to what extent, a person was responsible for the choice at the time of choosing, and asking the question of responsibility only once, we should ask whether, or to what extent, they are responsible for the choice at the point at which we are seeking to discover whether, or to what extent, the inequality is just, and so the question of responsibility is not settled but constantly under review. Such an approach will differ from Standard Luck Egalitarianism only if responsibility for a choice is not set in stone – if responsibility can weaken then we should not see the boundary between luck and responsibility within a particular action as static. Drawing on Derek Parfit’s illuminating discussions of personal identity, and contemporary literature on moral responsibility, I suggest there are good reasons to think that responsibility can weaken – that we are not necessarily fully responsible for a choice for ever, even if we were fully responsible at the time of choosing. I call the variant of luck egalitarianism that recognises this shift in temporal standpoint and that responsibility can weaken Dynamic Luck Egalitarianism (DLE). In conclusion I offer a preliminary discussion of what kind of policies DLE would support.

Panaméricas Utópicas: entranced and transient nations in 'I Am Cuba' and 'Land in Trance'

This Chapter looks at two political films, Land in Trance (Glauber Rocha, 1967) and I Am Cuba (Mikhail Kalatozov, 1964), which address the subject of the nation through the enactment of trance. Rejecting all forms of naturalistic account, both films adopt a series of anti-realist devices, such as poetic language, synecdoche, personification, parable and allegory, as a means of expanding the concept of the nation beyond territorial borders and conveying the meaning of revolution through the film form rather than its content.

Paraméricas Utópicas: entranced and transient nations in "I Am Cuba" (1964) and "Land in Anguish" (1967)

This article examines the astonishing similarities between two political films, Land in Trance (Glauber Rocha, 1967) and I Am Cuba (Mikhail Kalatozov, 1964). Both address the subject of revolution through the enactment of trance. Both reject all forms of naturalistic account, adopting a series of anti-realist devices, such as poetic language, synecdoche, personification, parable and allegory, as a means of expanding the concept of the nation beyond territorial borders and conveying the meaning of revolution through the film form, rather than its content. Because there is no evidence that Glauber Rocha had seen I Am Cuba before he shot Land in Trance, these coincidences are treated as an intellectual 'transit' between film-makers whose art was fuelled by cinephilia and the belief in the reality of the film medium.

Comparison of pollinators and natural enemies: a meta-analysis of landscape and local effects on abundance and richness in crops

To manage agroecosystems for multiple ecosystem services, we need to know whether the management of one service has positive, negative, or no effects on other services. We do not yet have data on the interactions between pollination and pest-control services. However, we do have data on the distributions of pollinators and natural enemies in agroecosystems. Therefore, we compared these two groups of ecosystem service providers, to see if the management of farms and agricultural landscapes might have similar effects on the abundance and richness of both. In a meta-analysis, we compared 46 studies that sampled bees, predatory beetles, parasitic wasps, and spiders in fields, orchards, or vineyards of food crops. These studies used the proximity or proportion of non-crop or natural habitats in the landscapes surrounding these crops (a measure of landscape complexity), or the proximity or diversity of non-crop plants in the margins of these crops (a measure of local complexity), to explain the abundance or richness of these beneficial arthropods. Compositional complexity at both landscape and local scales had positive effects on both pollinators and natural enemies, but different effects on different taxa. Effects on bees and spiders were significantly positive, but effects on parasitoids and predatory beetles (mostly Carabidae and Staphylinidae) were inconclusive. Landscape complexity had significantly stronger effects on bees than it did on predatory beetles and significantly stronger effects in non-woody rather than in woody crops. Effects on richness were significantly stronger than effects on abundance, but possibly only for spiders. This abundance-richness difference might be caused by differences between generalists and specialists, or between arthropods that depend on non-crop habitats (ecotone species and dispersers) and those that do not (cultural species). We call this the ‘specialist-generalist’ or ‘cultural difference’ mechanism. If complexity has stronger effects on richness than abundance, it might have stronger effects on the stability than the magnitude of these arthropod-mediated ecosystem services. We conclude that some pollinators and natural enemies seem to have compatible responses to complexity, and it might be possible to manage agroecosystems for the benefit of both. However, too few studies have compared the two, and so we cannot yet conclude that there are no negative interactions between pollinators and natural enemies, and no trade-offs between pollination and pest-control services. Therefore, we suggest a framework for future research to bridge these gaps in our knowledge.

Beyond urban legends : an emerging framework of urban ecology, as illustrated by the Baltimore Ecosystem Study

The emerging discipline of urban ecology is shifting focus from ecological processes embedded within cities to integrative studies of large urban areas as biophysical-social complexes. Yet this discipline lacks a theory. Results from the Baltimore Ecosystem Study, part of the Long Term Ecological Research Network, expose new assumptions and test existing assumptions about urban ecosystems. The findings suggest a broader range of structural and functional relationships than is often assumed for urban ecological systems. We address the relationships between social status and awareness of environmental problems, and between race and environmental hazard. We present patterns of species diversity, riparian function, and stream nitrate loading. In addition, we probe the suitability of land-use models, the diversity of soils, and the potential for urban carbon sequestration. Finally, we illustrate lags between social patterns and vegetation, the biogeochemistry of lawns, ecosystem nutrient retention, and social-biophysical feedbacks. These results suggest a framework for a theory of urban ecosystems.

Les dangers de la guerre. L'image du guerrier dans le Brut de La3amon

A study of the lexis and imagery of warfare in the early C13 English adaptation of Wace's Roman de Brut by the English poet La3amon. The narrator's stance is analysed the light of the poet's priestly identity, revealing an undercurrent of disapproval of the glorification of the warrior found in La3amon's sources, and moral concern for combatants engaged in 'unjust' wars of conquest.