Identification of SOX2 as a novel glioma-associated antigen and potential target for T cell-based immunotherapy

Prognosis for patients suffering from malignant glioma has not substantially improved. Specific immunotherapy as a novel treatment concept critically depends on target antigens, which are highly overexpressed in the majority of gliomas, but the number of such antigens is still very limited. SOX2 was identified by screening an expression database for transcripts that are overexpressed in malignant glioma, but display minimal expression in normal tissues. Expression of SOX2 mRNA was further investigated in tumour and normal tissues by real-time PCR. Compared to cDNA from pooled normal brain, SOX2 was overexpressed in almost all (9 out of 10) malignant glioma samples, whereas expression in other, non-malignant tissues was almost negligible. SOX2 protein expression in glioma cell lines and tumour tissues was verified by Western blot and immunofluorescence. Immunohistochemistry demonstrated SOX2 protein expression in all malignant glioma tissues investigated ranging from 6 to 66% stained tumour cells. Human leucocyte antigen-A*0201-restricted SOX2-derived peptides were tested for the activation of glioma-reactive CD8+ cytotoxic T lymphocytes (CTLs). Specific CTLs were raised against the peptide TLMKKDKYTL and were capable of lysing glioma cells. The abundant and glioma-restricted overexpression of SOX2 and the generation of SOX2-specific and tumour-reactive CTLs may recommend this antigen as target for T-cell-based immunotherapy of glioma

Effects of Elevated Temperature and Carbon Dioxide on the Growth and Survival of Larvae and Juveniles of Three Species of Northwest Atlantic Bivalves

Rising CO2 concentrations and water temperatures this century are likely to have transformative effects on many coastal marine organisms. Here, we compared the responses of two life history stages (larval, juvenile) of three species of calcifying bivalves (Mercenaria mercenaria, Crassostrea virginica, and Argopecten irradians) to temperatures (24 and 28°C) and CO2 concentrations (∼250, 390, and 750 ppm) representative of past, present, and future summer conditions in temperate estuaries. Results demonstrated that increases in temperature and CO2 each significantly depressed survival, development, growth, and lipid synthesis of M. mercenaria and A. irradians larvae and that the effects were additive. Juvenile M. mercenaria and A. irradians were negatively impacted by higher temperatures while C. virginica juveniles were not. C. virginica and A. irradians juveniles were negatively affected by higher CO2 concentrations, while M. mercenaria was not. Larvae were substantially more vulnerable to elevated CO2 than juvenile stages. These findings suggest that current and future increases in temperature and CO2 are likely to have negative consequences for coastal bivalve populations

Subjectivity in a context of environmental change: opening new dialogues in mental health research

In a period of unstable experimentation with challenges of globalization of associated risks, and disenchantment with ‘enduring injustice’, we bring forward a consideration of subjectivity to the study of environmental change and mental health. We begin by identifying how mainstream climate change and mental health studies are unable to explain the emergent and co-evolutionary pathways of agency. As a means of freeing these studies of their objective dimensions of linear-causation, we argue in favour of a re-positioning of subjectivity within an appreciation of recognition conflicts and beyond the over-deterministic interpretations of power centres—state, market or religion. We draw on one example of scientific research that was conducted in a region undergoing strong environmental, social and cultural changes, in the state of São Paulo/Brazil, with the aim to open mental health research to new dialogues, to which we contribute with the notion of the ‘pluriversal subject’

Strengthening conceptual foundations: Analysing frameworks for ecosystem services and poverty alleviation research

AbstractA research agenda is currently developing around the linkages between ecosystem services and poverty alleviation. It is therefore timely to consider which conceptual frameworks can best support research at this nexus. Our review of frameworks synthesises existing research on poverty/environment linkages that should not be overlooked with the adoption of the topical language of ecosystem services. A total of nine conceptual frameworks were selected on the basis of relevance. These were reviewed and compared to assess their ability to illuminate the provision of ecosystem services, the condition, determinants and dynamics of poverty, and political economy factors that mediate the relationship between poverty and ecosystem services. The paper synthesises the key contributions of each of these frameworks, and the gaps they expose in one another, drawing out lessons that can inform emerging research. Research on poverty alleviation must recognize social differentiation, and be able to distinguish between constraints of access and constraints of aggregate availability of ecosystem services. Different frameworks also highlight important differences between categories of services, their pathways of production, and their contribution to poverty alleviation. Furthermore, we highlight that it is important to acknowledge the limits of ecosystem services for poverty alleviation, given evidence that ecosystem services tend to be more associated with poverty prevention than reduction. We conclude by reflecting on the relative merits of dynamic Social–Ecological Systems frameworks versus more static checklists, and suggest that research on ecosystem services and poverty alleviation would be well served by a new framework distilling insights from the frameworks we review

Association of the TNFa13 microsatellite with systemic sclerosis in Japanese patients

OBJECTIVES—To elucidate the contribution of microsatellite polymorphisms of TNFa and TNFb alleles to the pathogenesis of systemic sclerosis (SSc) by comparing the allele distribution among populations with different HLA susceptibility genes in SSc.
METHODS—TNFa and TNFb microsatellite polymorphisms were determined by PCR in 54 Japanese and 50 German SSc patients and in normal controls. HLA-DR genotyping was carried out by PCR-SSCP.
RESULTS—The frequency of TNFa13 was significantly increased in Japanese SSc (p=0.011, OR=8.53, 95% confidence intervals (95%CI)=2.46, 32.51, and p<1.0 × 10E-5, OR=10.35, 95%CI=4.88, 22.09) and SSc with antitopoisomerase I antibody (a-Scl-70) (p=0.021, OR=33.25, 95%CI=3.39, 800.76, and p<1.0 × 10E-5, OR=24.42, 95%CI=8.40, 72.83), compared with the German patient group and German controls, respectively. This increase was not only attributable to a higher prevalence of TNFa13 in Japanese compared with Germans (p=0.005, OR=3.55, 95%CI=1.60, 7.85) but was also caused by an increase in SSc, especially in the a-Scl-70 positive patients (p=0.028, OR=6.88, 95%CI=1.16, 22.60) compared with Japanese controls. TNFa13 was positively in linkage disequilibrium with HLA-DRB1*1502 (LD=0.053, t=2.69). Association analysis indicated that both TNFa13 and DRB1*1502 might have comparable probabilities of being susceptibility factors for SSc with a-Scl-70 in Japanese. Prevalences of TNFa6 and 13( )were significantly increased and prevalences of TNFa2, and 7 were significantly decreased in Japanese controls as compared with German controls.
CONCLUSION—TNFa13 is a genetic marker for SSc with a-Scl-70 in Japanese patients. Various differences in the prevalences of TNFa alleles between Japanese and German controls were established.