Functional role of endothelial adhesion molecules in the early stages of brain metastasis

BACKGROUND: Cellular adhesion molecules (CAMs), which are normally associated with leukocyte trafficking, have also been shown to play an essential role in tumor metastasis to non-CNS sites. However, the role played by CAMs in brain metastasis is largely unexplored. It is known that leukocyte recruitment to the brain is very atypical and that mechanisms of disease in peripheral tissues cannot be extrapolated to the brain. Here, we have established the spatiotemporal expression of 12 key CAMs in the initial phases of tumor seeding in 2 different models of brain metastasis. METHODS: BALB/c or SCID mice were injected intracardially (10(5) cells/100 μL phosphate-buffered saline with either 4T1-GFP or MDA231BR-GFP cells, respectively (n = 4–6/group), and expression of the CAMs was determined by immunohistochemistry and immunofluorescence colocalisation. RESULTS: Endothelial expression of E-selectin, VCAM-1, ALCAM, ICAM-1, VLA-4, and β(4) integrin was markedly increased early in tumor seeding. At the same time, the natural ligands to these adhesion molecules were highly expressed on the metastatic tumor cells both in vitro and in vivo. Two of these ligands showed particularly high tumor cell expression (ALCAM and VLA-4), and consequently their functional role in tumor seeding was determined. Antibody neutralization of either ALCAM or VLA-4 significantly reduced tumor seeding within the brain (>60% decrease in tumor number/mm(2) brain; P < .05–0.01). CONCLUSIONS: These findings suggest that ALCAM/ALCAM and VLA-4/VCAM-1 interactions play an important functional role in the early stages of metastasis seeding in the brain. Moreover, this work identifies a specific subset of ligand-receptor interactions that may yield new therapeutic and diagnostic targets for brain metastasis

Fit for purpose? Pattern cutting and seams in wearables development

This paper describes how a group of practitioners and researchers are working across disciplines at Nottingham Trent University in the area of Technical Textiles. It introduces strands of ongoing enquiry centred around the development and application of stretch sensors on the body, focusing on how textile and fashion knowledge are being reflexively revealed in the collaborative development of seamful wearable concepts, and on the tensions between design philosophies as revealed by definitions of purpose. We discuss the current research direction of the Aeolia project, which seeks to exploit the literal gaps found in pattern cutting for fitted stretch garments towards experiential forms and potential interactions. Normative goals of fitness for purpose and seamlessness are interrogated and the potential for more integrated design processes, which may at first appear ‘upside down’, is discussed

Negotiating the inhuman: Bakhtin, materiality and the instrumentalization of climate change

The article argues that the work of literary theorist Mikhail M. Bakhtin presents a starting point for thinking about the instrumentalization of climate change. Bakhtin’s conceptualization of human–world relationships, encapsulated in the concept of ‘cosmic terror’, places a strong focus on our perception of the ‘inhuman’. Suggesting a link between the perceived alienness and instability of the world and in the exploitation of the resulting fear of change by political and religious forces, Bakhtin asserts that the latter can only be resisted if our desire for a false stability in the world is overcome. The key to this overcoming of fear, for him, lies in recognizing and confronting the worldly relations of the human body. This consciousness represents the beginning of one’s ‘deautomatization’ from following established patterns of reactions to predicted or real changes. In the vein of several theorists and artists of his time who explored similar ‘deautomatization’ strategies – examples include Shklovsky’s ‘ostranenie’, Brecht’s ‘Verfremdung’, Artaud’s emotional ‘cruelty’ and Bataille’s ‘base materialism’ – Bakhtin proposes a more playful and widely accessible experimentation to deconstruct our ‘habitual picture of the world’. Experimentation is envisioned to take place across the material and the textual to increase possibilities for action. Through engaging with Bakhtin’s ideas, this article seeks to draw attention to relations between the imagination of the world and political agency, and the need to include these relations in our own experiments with creating climate change awareness

Retreating to nature : rethinking 'therapeutic landscapes'

There is a long history of removing oneself from ‘society’ in order to recuperate or repair. This paper considers a yoga and massage retreat in Southern Spain, and what opportunities this retreat experience might offer for recuperation and the creation of healthy bodies. The paper positions ‘nature’ as an active participant, and as ‘enrolled’ in the experiences of the retreat as a ‘therapeutic landscape’, and questions how and what particular aspects of yoga practice (in intimate relation with place) give rise to therapeutic experiences

PHOSPHORUS-STARVATION TOLERANCE 1 (OsPSTOL1) is prevalent in upland rice and enhances root growth and hastens low phosphate signaling in wheat

PHOSPHORUS-STARVATION TOLERANCE 1 (OsPSTOL1) is a variably present gene that benefits crown root growth and phosphorus (P) sufficiency in rice (Oryza sativa). To explore the ecophysiological importance of this gene, we performed a biogeographic survey of landraces and cultivars, confirming that functional OsPSTOL1 alleles prevail in low nutrient and drought-prone rainfed ecosystems, whereas loss-of-function and absence haplotypes predominate in control-irrigated paddy varieties of east Asia. An evolutionary history analysis of OsPSTOL1 and related genes in cereal, determined it and other genes are kinase-only domain derivatives of membrane-associated receptor like kinases. Finally, to evaluate the potential value of this kinase of unknown function in another Gramineae, wheat (Triticum aestivum) lines overexpressing OsPSTOL1 were evaluated under field and controlled low P conditions. OsPSTOL1 enhances growth, crown root number, and overall root plasticity under low P in wheat. Survey of root and shoot crown transcriptomes at two developmental stages identifies transcription factors that are differentially regulated in OsPSTOL1 wheat that are similarly controlled by the gene in rice. In wheat, OsPSTOL1 alters the timing and amplitude of regulators of root development in dry soils and hastens induction of the core P-starvation response. OsPSTOL1 and related genes may aid more sustainable cultivation of cereal crops

Athrombocytopenic thrombotic microangiopathy, a condition that could be overlooked based on current diagnostic criteria

Background. Thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS) are thrombotic microangiopathies (TMAs). They are generally diagnosed and treated by plasmapheresis in the presence of non-immune haemolytic anaemia and thrombocytopenia. Yet, many individuals admitted in our hospital for athrombocytopenic renal failure of unknown cause were reported to have TMA as main lesion on kidney biopsies