Immunoreceptors: evolution,structure and therapeutic applications

The ‘Immunoreceptors’ meeting took place in July 2012 in beautiful Snowmass Village in Colorado, USA. At an altitude of more than two kilometres, researchers and clinicians discussed the molecular aspects of immunoreceptors, ranging from B‐ and T‐cell receptors, to complement and Fc receptors.     

‘Make-up’: Personhood through the lens of biotechnology

This paper looks through the ethnographic lens of ‘new reproductive and genetic technologies’ (NRGT) at the idiom of ‘make-up’ in English understandings of personhood and relatedness. In the kinship thinking of interest here, persons are both ‘made’ and ‘made-up’. There are both unpredictable and inevitable elements in the way in which people ‘turn-out’ and their character or personality is meant to be idiosyncratic, lumpy and unique. The paper draws on the way in which residents of a town in the north of England explore possibilities presented by NRGT in ways that make explicit their understandings of personal identity, interpersonal relatedness and communal belonging. The paper attempts to integrate the quotidian and personal narratives of residents with broader social and economic changes occurring in their town.     

Shedding of Endogenous Interleukin-6 Receptor (IL-6R) Is Governed by A Disintegrin and Metalloproteinase (ADAM) Proteases while a Full-length IL-6R Isoform Localizes to Circulating Microvesicles

Generation of the soluble interleukin-6 receptor (sIL-6R) is a prerequisite for pathogenic IL-6 trans-signaling, which constitutes a distinct signaling pathway of the pleiotropic cytokine interleukin-6 (IL-6). Although in vitro experiments using ectopically overexpressed IL-6R and candidate proteases revealed major roles for the metalloproteinases ADAM10 and ADAM17 in IL-6R shedding, the identity of the protease(s) cleaving IL-6R in more physiological settings, or even in vivo, remains unknown. By taking advantage of specific pharmacological inhibitors and primary cells from ADAM-deficient mice we established that endogenous IL-6R of both human and murine origin is shed by ADAM17 in an induced manner, whereas constitutive release of endogenous IL-6R is largely mediated by ADAM10. Although circulating IL-6R levels are altered in various diseases, the origin of blood-borne IL-6R is still poorly understood. It has been shown previously that ADAM17 hypomorphic mice exhibit unaltered levels of serum sIL-6R. Here, by quantification of serum sIL-6R in protease-deficient mice as well as human patients we also excluded ADAM10, ADAM8, neutrophil elastase, cathepsin G, and proteinase 3 from contributing to circulating sIL-6R. Furthermore, we ruled out alternative splicing of the IL-6R mRNA as a potential source of circulating sIL-6R in the mouse. Instead, we found full-length IL-6R on circulating microvesicles, establishing microvesicle release as a novel mechanism for sIL-6R generation.     

Monoclonal anti-β1-adrenergic receptor antibodies activate G protein signaling in the absence of β-arrestin recruitment

Thermostabilized G protein-coupled receptors used as antigens for in vivo immunization have resulted in the generation of functional agonistic anti-β₁-adrenergic (β₁AR) receptor monoclonal antibodies (mAbs). The focus of this study was to examine the pharmacology of these antibodies to evaluate their mechanistic activity at β₁AR. Immunization with the β₁AR stabilized receptor yielded five stable hybridoma clones, four of which expressed functional IgG, as determined in cell-based assays used to evaluate cAMP stimulation. The antibodies bind diverse epitopes associated with low nanomolar agonist activity at β₁AR, and they appeared to show some degree of biased signaling as they were inactive in an assay measuring signaling through β-arrestin. In vitro characterization also verified different antibody-receptor interactions reflecting the different epitopes on the extracellular surface of β₁AR to which the mAbs bind. The anti-β₁AR mAbs only demonstrated agonist activity when in dimeric antibody format, but not as the monomeric Fab format, suggesting that agonist activation may be mediated through promoting receptor dimerization. Finally, we have also shown that at least one of these antibodies exhibits in vivo functional activity at a therapeutically-relevant dose producing an increase in heart rate consistent with β₁AR agonism.     

A Feel for Genealogy: ‘Family Treeing’ in the North of England

Family history research is popular in England. As a social practice it straddles social class and is confined to neither the middle nor the working classes, but shows an enthusiastic and flourishing interest in the workings of social class and in micro-histories of the region. This article focuses on experts in family history research in a region of the north west of England where it is referred to colloquially as ‘family treeing’. Here family treeing is inflected by a post-industrial landscape and recent social and economic transformations with attendant threats to working-class life and dignity. Family treeing is about caring for the dead, but it is also, significantly, about caring for the living, and not only kin. It is an active practice of belonging both to people and places, and entails constant acts of reciprocity.     

Seed limitation,not soil legacy effects,prevents native understorey from establishing in oak woodlands in Scotland after removal of Rhododendron ponticum

Following removal of the invasive species Rhododendron ponticum, the native understorey plant community typically fails to reestablish itself. Potential explanations for this failure include (1) lack of an appropriate native seed source; (2) inability of seed to penetrate a dense bryophyte layer; and (3) persistence of chemical “legacy effects” in the soil. We established an experiment to test these competing hypotheses in an Atlantic oak woodland where R. ponticum had been removed. The following experimental treatments were applied singly and in combination: (1) addition of a native seed mix to test for seed limitation; (2) removal of the established ground vegetation at the start of the experiment (which principally consisted of bryophytes) to test for the impact of a barrier layer; (3) addition of activated carbon to test for chemical legacy effects in the soil; and (4) fertilization as an additional measure to promote the establishment of native vascular plants. Application of the native seed mix was revealed to be an effective way to increase the cover of native vascular plants and was particularly effective when applied after the removal of the bryophyte layer. The application of activated carbon and/or fertilizer, however, had no effect on the cover of native vegetation. We conclude that reports of R. ponticum exerting chemical legacy effects long after its removal may have been overstated and that seed limitation and inability to successfully establish in a dense bryophyte layer provided the strongest barriers to natural recolonization by the native plant community following R. ponticum removal.     

Environmental conditions and herbivore biomass determine coral reef benthic community composition: implications for quantitative baselines

Coral Reefs - Our ability to understand natural constraints on coral reef benthic communities requires quantitative assessment of the relative strengths of abiotic and biotic processes across large...     

Do ectomycorrhizal fungi exhibit adaptive tolerance to potentially toxic metals in the environment ?

The effects of potentially toxic metals on ectomycorrhizal (ECM) fungi and their higher plant hosts are examined in this review. Investigations at a species and community level have revealed wide inter- and intraspecific variation in sensitivity to metals. Adaptive and constitutive mechanisms of ECM tolerance are proposed and discussed in relation to proven tolerance mechanisms in bacteria, yeasts and plants. Problems with methodology and research priorities are highlighted. These include the need for a detailed understanding of the genetic basis of tolerance in the ECM symbiosis, and for studies of ECM community dynamics in polluted sites.     

The Idea of Power and the Power of Ideas: A Review Essay

In Envisioning Power , the late Eric Wolf, one of anthropology's most renowned practitioners, argues that the time has come to fuse power to ideas, not least of all in order to revitalize the concept of culture. His argument is explored in three notable case studies: the Kwakiutl, the Aztecs, and National Socialism in Germany. Our main criticism is that the concept of structural power favored by Wolf is redundant and expendable, partly because the case studies, while elegantly presented, are inappropriate for the author's theoretical interests, [power, culture, conflict]     

Scaling of maximal oxygen uptake by lower leg muscle volume in boys and men.

The aim of this study was to critically examine the influence of body size on maximal oxygen uptake (VO2 max) in boys and men using body mass (BM), estimated fat-free mass (FFM), and estimated lower leg muscle volume (Vol) as the separate scaling variables. VO2 max and an in vivo measurement of Vol were assessed in 15 boys and 14 men. The FFM was estimated after percentage body fat had been predicted from population-specific skinfold measurements. By using nonlinear allometric modeling, common body size exponents for BM, FFM, and Vol were calculated. The point estimates for the size exponent (95% confidence interval) from the separate allometric models were: BM 0.79 (0.53-1.06), FFM 1.00 (0.78-1.22), and Vol 0.64 (0.40-0.88). For the boys, substantial residual size correlations were observed for VO2 max/BM0.79 and VO2 max/FFM1.00, indicating that these variables did not correctly partition out the influence of body size. In contrast, scaling by Vol0.64 led to no residual size correlation in boys or men. Scaling by BM is confounded by heterogeneity of body composition and potentially substantial differences in the mass exponent between boys and men. The FFM is precluded as an index of involved musculature because Vol did not represent a constant proportion of FFM [Vol proportional, variantFFM1.45 (95% confidence interval, 1.13-1.77)] in the boys (unlike the men). We conclude that Vol, as an indicator of the involved muscle mass, is the most valid allometric denominator for the scaling of VO2 max in a sample of boys and men heterogeneous for body size and composition.