Melanoma Cell Expression of CD200 Inhibits Tumor Formation and Lung Metastasis via Inhibition of Myeloid Cell Functions

CD200 is a cell surface glycoprotein that functions through engaging CD200 receptor on cells of the myeloid lineage and inhibits their functions. Expression of CD200 has been implicated in a variety of human cancer cells including melanoma cells and has been thought to play a protumor role. To investigate the role of cancer cell expression of CD200 in tumor formation and metastasis, we generated CD200-positive and CD200-negative B16 melanoma cells. Subcutaneous injection of CD200-positive B16 melanoma cells inhibited tumor formation and growth in C57BL/6 mice but not in Rag1−/−C57BL/6 mice. However, i.v. injection of CD200-positive B16 melanoma cells dramatically inhibited tumor foci formation in the lungs of both C57BL/6 and Rag1−/−C57BL6 mice. Flow cytometry analysis revealed higher expression of CD200R in Gr1+ myeloid cells in the lung than in peripheral myeloid cells. Depletion of Gr1+ cells or stimulation of CD200R with an agonistic antibody in vivo dramatically inhibited tumor foci formation in the lungs. In addition, treatment with tumor antigen specific CD4 or CD8 T cells or their combination yielded a survival advantage for CD200 positive tumor bearing mice over mice bearing CD200-negative tumors. Taken together, we have revealed a novel role for CD200-CD200R interaction in inhibiting tumor formation and metastasis. Targeting CD200R may represent a novel approach for cancer immunotherapy

Thermal limits of burrowing capacity are linked to oxygen availability and size in the Antarctic clam Laternula elliptica

Animal responses to changing environments are most commonly studied in relation to temperature change. The current paradigm for marine ectotherms is that temperature limits are set through oxygen limitation. Oxygen limitation leads to progressive reductions in capacity to perform work or activity, and these are more important and proximate measures of a population’s ability to survive. Here we measured the ability of a large Antarctic clam to rebury when removed from sediment at temperatures between −1.5 and 7.5 °C and at three oxygen concentrations, 10.2, 20.5 and 27.7%. The proportion of the population capable of reburying declined rapidly and linearly with temperature from around 65% at 0 °C to 0% at 6 °C in normoxia (20.5% O2). Decreasing oxygen to 10.2% reduced temperature limits for successful burial by around 2 °C, and increasing oxygen to 27.7% raised the limits by 1–1.5 °C. There was an interactive effect of body size and temperature on burying: the temperature limits of larger individuals were lower than smaller animals. Similarly, these size limits were increased by increasing oxygen availability. Considering data for all temperatures and oxygen levels, the fastest burying rates occurred at 3 °C, which is 2 °C above the maximum summer temperature at this site

A Re-assessment of Narragansett Bay Benthic Habitat Quality Between 1988 and 2008

The first bay-wide synoptic survey of benthic habitat quality in Narragansett Bay, Rhode Island, USA, was conducted in August of 1988. Twenty years later, we revisited the same sampling locations as the original survey using similar sediment profile imagery technology and analysis tools. Like estuaries throughout the US, increased temperatures and reductions to anthropogenic nutrient inputs have cumulatively affected Narragansett Bay in the intervening 20 years. To understand how these changes may have influenced benthic organic enrichment and habitat quality, we compared the prevalence and spatial arrangement of benthic biotopes (i.e., biotic and abiotic benthic descriptions) between 1988 and 2008 surveys. Biotopes dominated by Ampelisca spp. tubiculous amphipods increased \u3efivefold between 1988 and 2008, and expanded into the more urban, anthropogenically stressed Providence River estuary. Ampelisca beds occurred at critical boundaries in organic enrichment and habitat quality in both years and indicated the quantity of organic matter reaching the benthos. In general, benthic biotopes reflect the degree of benthic-pelagic coupling and are an important link between estuarine water quality and other marine life. As estuaries globally cope with the effects of increased warming and legislated anthropogenic nutrient reductions, rapid assessments of benthic biotopes will be critical for understanding changes to whole-estuary condition as a result of these cumulative stressors

Value assessment and pricing capabilities-how to profit from value

Value is a key concept for researchers and practitioners in the fields of strategy, marketing, and pricing. In the strategy literature, value is closely related to competitive advantage and profit, in the marketing literature value is the cornerstone of the marketing management process, in the pricing literature value represents the customer's willingness to pay. The aim of this article is to bridge the gap between marketing, pricing and strategy research through a compilation of five short essays that focus on value assessment and pricing capabilities. This article argues that value assessment and pricing capabilities provide the foundation for value creation and value appropriation in business-to-business markets, highlights their implications for profiting from value created and delivered, and outlines important areas for future research

Influenza infection induces host DNA damage and dynamic DNA damage responses during tissue regeneration

Influenza viruses account for significant morbidity worldwide. Inflammatory responses, including excessive generation of reactive oxygen and nitrogen species (RONS), mediate lung injury in severe influenza infections. However, the molecular basis of inflammation-induced lung damage is not fully understood. Here, we studied influenza H1N1 infected cells in vitro, as well as H1N1 infected mice, and we monitored molecular and cellular responses over the course of 2 weeks in vivo. We show that influenza induces DNA damage to both, when cells are directly exposed to virus in vitro (measured using the comet assay) and also when cells are exposed to virus in vivo (estimated via γH2AX foci). We show that DNA damage, as well as responses to DNA damage persist in vivo until long after virus has been cleared, at times when there are inflammation associated RONS (measured by xanthine oxidase activity and oxidative products). The frequency of lung epithelial and immune cells with increased γH2AX foci is elevated in vivo, especially for dividing cells (Ki-67-positive) exposed to oxidative stress during tissue regeneration. Additionally, we observed a significant increase in apoptotic cells as well as increased levels of DNA double strand break (DSB) repair proteins Ku70, Ku86 and Rad51 during the regenerative phase. In conclusion, results show that influenza induces DNA damage both in vitro and in vivo, and that DNA damage responses are activated, raising the possibility that DNA repair capacity may be a determining factor for tissue recovery and disease outcome.Singapore National Research Foundatio