Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys

We transplanted kidneys from α1,3-galactosyltransferase knockout (GalT-KO) pigs into six baboons using two different immunosuppressive regimens, but most of the baboons died from severe acute humoral xenograft rejection. Circulating induced antibodies to non-Gal antigens were markedly elevated at rejection, which mediated strong complement-dependent cytotoxicity against GalT-KO porcine target cells. These data suggest that antibodies to non-Gal antigens will present an additional barrier to transplantation of organs from GalT-KO pigs to humans. © 2005 Nature Publishing Group

Cord blood banking – bio-objects on the borderlands between community and immunity

Umbilical cord blood (UCB) has become the focus of intense efforts to collect, screen and bank haematopoietic stem cells (HSCs) in hundreds of repositories around the world. UCB banking has developed through a broad spectrum of overlapping banking practices, sectors and institutional forms. Superficially at least, these sectors have been widely distinguished in bioethical and policy literature between notions of the ‘public’ and the ‘private’, the commons and the market respectively. Our purpose in this paper is to reflect more critically on these distinctions and to articulate the complex practical and hybrid nature of cord blood as a ‘bio-object’ that straddles binary conceptions of the blood economies. The paper draws upon Roberto Esposito’s reflections on biopolitics and his attempt to transcend the dualistic polarisations of immunity and community, or the private and the public. We suggest that his thoughts on immunitary hospitality resonate with many of the actual features and realpolitik of a necessarily internationalised and globally distributed UCB ‘immunitary regime’

The image after Strathern:Art and persuasive relationality in India's sanguinary politics

Publicly-enacted blood extractions (principally blood donation events and petitions or paintings in blood) in mass Indian political contexts (for instance, protest or political memorial events and election rallies) are a noteworthy present-day form of political enunciation in India, for such extractions – made to speak as and on behalf of political subject positions – are intensely communicative. Somewhat akin to the transformative fasts undertaken by Gandhi, such blood extractions seek to persuade from the moral high ground of political asceticism. This essay seeks to shed light on how and why these extractions have become such a means, with a particular focus on blood-based portraiture. What makes such portraits – chiefly of politicians and ‘freedom fighter’ martyrs – interesting from a Strathernian point of view is their immanent persuasive relationality. The insights of Strathern can help us to explicate these objects’ dynamic relational features, while reciprocally, the portraits may help us to illuminate and clarify the very particular and interesting nature of the way Strathern treats (and creates) images

Garotas de loja, história social e teoria social [Shop Girls, Social History and Social Theory]

Shop workers, most of them women, have made up a significant proportion of Britain’s labour force since the 1850s but we still know relatively little about their history. This article argues that there has been a systematic neglect of one of the largest sectors of female employment by historians and investigates why this might be. It suggests that this neglect is connected to framings of work that have overlooked the service sector as a whole as well as to a continuing unease with the consumer society’s transformation of social life. One element of that transformation was the rise of new forms of aesthetic, emotional and sexualised labour. Certain kinds of ‘shop girls’ embodied these in spectacular fashion. As a result, they became enduring icons of mass consumption, simultaneously dismissed as passive cultural dupes or punished as powerful agents of cultural destruction. This article interweaves the social history of everyday shop workers with shifting representations of the ‘shop girl’, from Victorian music hall parodies, through modernist social theory, to the bizarre bombing of the Biba boutique in London by the Angry Brigade on May Day 1971. It concludes that progressive historians have much to gain by reclaiming these workers and the service economy that they helped create

Prolonged response to first-line erlotinib for advanced lung adenocarcinoma

A 58-year-old, non-smoking female of Philippine origin presented with painful thoracic and neck nodal relapse of lung adenocarcinoma almost 5 years after left pneumonectomy for stage II non-small-cell lung cancer. She refused conventional chemotherapy or radiation because of toxicity concerns, but agreed to oral erlotinib 150 mg/day. Within weeks, her pain was well controlled, with softening of palpable neck nodes. Repeat scans after 7 months on erlotinib showed partial response of thoracic disease and nodal metastases. This response was maintained for 11 months on erlotinib, with symptomatic progression at the original sites of relapse by 15 months. Erlotinib was well tolerated, with grade 2–3 rash, and grade 1 dry cough and diarrhoea being the only significant toxicities. Importantly, the patient was able to maintain daily activities throughout erlotinib therapy

Total Lipids, Lipid Classes, and Fatty Acids of Newly Settled Red King Crab (Paralithodes camtschaticus): Comparison of hatchery-cultured and wild crabs

Little is known about the nutrition or lipid metabolism of cold-water crabs, particularly in the North Pacific. We undertook a 2-part study to understand more completely the energetics and nutritional requirements of juvenile red king crab (RKC; Paralithodes canusehaticus). First, we investigated changes in proximate composition, total lipids (TLs), lipid classes, and fatty acids (FAs) throughout a molt cycle (C4-C5). Trends in lipid parameters were described by a 3-pari, piecewise linear regression with 3 distinct stages: (I) a postmolt phase (similar to 0-7 days), (2) an intramolt stage (similar to 7-24 days), and (3) a premolt stage (similar to 24-33 days). Significant intramolt differences in TLs indicated that caution should be taken when comparing crabs of unknown molt stage in future aquaculture and ecological experiments. However, little variability was found in the proportional FA composition of crabs, indicating that the intramolt stage has little effect on the interpretation of FA biomarkers. During a second investigation, we examined differences in lipid classes and FAs from cultured and wild RKC. We found significantly higher proportions of the essential fatty acids (EFAs) 20:5n-3 (EPA) and 20:4n-6 (AA) in wild crabs compared with cultured animals at the same stage. Furthermore, higher proportions of bacterial markers and lower proportions of zooplankton FA markers were found in wild than in hatchery-reared crabs. Here, we provide the first baseline data for future dietary studies on juvenile cold-water crabs. We suggest that an initial EFA ratio for DHA:EPA:AA of 5:8:1 could be used as a starting point for controlled dietary studies on the effect of EFAs on juvenile growth, molt success, and survival.Keywords: Lipids, Nutrition, Red king crab, Paralithodes camtschaticus, Fatty acids, Mol

The circumpolar impacts of climate change and anthropogenic stressors on Arctic cod (Boreogadus saida) and its ecosystem

Arctic cod (Boreogadus saida) is the most abundant forage fish in the Arctic Ocean. Here we review Arctic cod habitats, distribution, ecology, and physiology to assess how climate change and other anthropogenic stressors are affecting this key species. This review identifies vulnerabilities for different life stages across the entire distribution range of Arctic cod. We explore the impact of environmental (abiotic and biotic) and anthropogenic stressors on Arctic cod with a regional perspective in a scenario up to the year 2050 and identify knowledge gaps constraining predictions. Epipelagic eggs and larvae are more vulnerable to climate change and stressors than adults. Increased water temperatures, sea-ice decline, altered freshwater input, acidification, changing prey field, increased interspecific competition, new predators, and pollution are the principal stressors that will affect Arctic cod populations. Detrimental effects are likely to be greater in regions characterized by the advection of warmer Atlantic and Pacific waters. In contrast, Arctic cod may benefit from ocean warming in colder areas of the High Arctic. The risk from fisheries is moderate and primarily limited to bycatch. Overall, a decrease in suitable habitat and an associated decline in total Arctic cod biomass are predicted. In most Arctic seas, the relative abundance of Arctic cod within the fish community will likely fluctuate in accordance with cold and warm periods. A reduced abundance of Arctic cod will negatively affect the abundance, distribution, and physiological condition of certain predators, whereas some predators will successfully adapt to a more boreal diet. Regional management measures that recognize the critical role of Arctic cod are required to ensure that increased anthropogenic activities do not exacerbate the impacts of climate change on Arctic marine ecosystems. Ultimately, the mitigation of habitat loss for Arctic cod will only be achieved through a global reduction in carbon emissions

The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study

Midostaurin (PKC412A), N-benzoyl-staurosporine, potently inhibits protein kinase C alpha (PKCα), VEGFR2, KIT, PDGFR and FLT3 tyrosine kinases. In mice, midostaurin slows growth and delays lung metastasis of melanoma cell lines. We aimed to test midostaurin's safety, efficacy and biologic activity in a Phase IIA clinical trial in patients with metastatic melanoma. Seventeen patients with advanced metastatic melanoma received midostaurin 75 mg p.o. t.i.d., unless toxicity or disease progression supervened. Patient safety was assessed weekly, and tumour response was assessed clinically or by CT. Tumour biopsies and plasma samples obtained at entry and after 4 weeks were analysed for midostaurin concentration, PKC activity and multidrug resistance. No tumour responses were seen. Two (12%) patients had stable disease for 50 and 85 days, with minor response in one. The median overall survival was 43 days. Seven (41%) discontinued treatment with potential toxicity, including nausea, vomiting, diarrhoea and/or fatigue. One patient had >50% reduction in PKC activity. Tumour biopsies showed two PKC isoforms relatively insensitive to midostaurin, out of three patients tested. No modulation of multidrug resistance was demonstrated. At this dose schedule, midostaurin did not show clinical or biologic activity against metastatic melanoma. This negative trial reinforces the importance of correlating biologic and clinical responses in early clinical trials of targeted therapies

Ontogenetic and spatial variability in trophic biomarkers of juvenile saffron cod (Eleginus gracilis) from the Beaufort, Chukchi and Bering Seas

Climate models indicate the Arctic will undergo dramatic environmental change with forecasted increases in temperature and river runoff. Saffron cod (Eleginus gracilis) is abundant in nearshore waters and appears in the diet of many Arctic sea birds and marine mammals; however, little is known about its early ecology and consequently how they might be affected by environmental changes. We aimed to characterize the mechanisms of spatial and ontogenetic variation in trophic biomarkers (lipid classes, fatty acids and bulk C and N stable isotopes) of saffron cod from the Western Arctic, Chukchi and Bering Seas. Size-standardized analyses showed a significant difference in lipid condition metrics and trophic biomarkers as a function of survey location. Both ontogeny and sampling location played an important role in determining lipid stores with elevated levels in both small offshore juveniles (75 mm). Higher lipid storage in Arctic juveniles was associated with elevated levels of diatom fatty acid markers, but not with nearshore carbon input. Increased lipids were found in age-1 juveniles from Prudhoe Bay in the Western Beaufort that were feeding at a lower trophic level than similarly sized age-0 juveniles from surface trawls in the Bering Sea. The use of otolith annuli revealed two discrete patterns of growth that help explain the trade-offs between energy storage and rapid growth that diverge between the Arctic and Bering Sea. Laboratory temperature-growth experiments confirmed that saffron cod have a eurythermal growth response and are able to store excess lipids at temperatures as high as 20°C.Keywords: Arctic, Nutrition, Fatty acids, Saffron cod, Lipids, OntogenyKeywords: Arctic, Nutrition, Fatty acids, Saffron cod, Lipids, Ontogen