Public Reason that Speaks to People : Iris Marion Young and the Problem of Internal Exclusion

Dossier : In Memoriam, Iris Marion Young (1949-2006

Citizens Without Robes: On the Deliberative Potential of Everyday Politics

This essay is a sympathetic critical comment on Cristina Lafont’s recent book, Democracy without Shortcuts: A Participatory Conception of Deliberative Democracy. I focus primarily on the arguments in the final chapters of the book that introduce a deliberative democratic re-interpretation of judicial review. Lafont appeals to the evocative imagery of citizens in robes and suggests that contesting legislation at the level of the supreme court does not take questions out of the public sphere and into the legal domain but rather brings questions of right and constitutionality into the political domain. The institutional possibility for individual citizens to challenge any law and thus launch a broad public debate that demands justifications and reasons is the heart of Lafont’s conception of participatory deliberative democracy. I find this a powerful and compelling defense and understanding of judicial review. I question, however, what appears to be a narrowing of deliberative democracy to constitutional contestation and so an abandonment of everyday politics where issues, debates, and controversies are not structured by the constraint of constitutional discourse. I argue that the focus on constitutional politics, made necessarily by her public reason requirement, narrows the range of her theory and appears to leave everyday politics outside the scope of deliberative democracy

Network reconstruction for trans acting genetic loci using multi-omics data and prior information

BACKGROUND: Molecular measurements of the genome, the transcriptome, and the epigenome, often termed multi-omics data, provide an in-depth view on biological systems and their integration is crucial for gaining insights in complex regulatory processes. These data can be used to explain disease related genetic variants by linking them to intermediate molecular traits (quantitative trait loci, QTL). Molecular networks regulating cellular processes leave footprints in QTL results as so-called trans-QTL hotspots. Reconstructing these networks is a complex endeavor and use of biological prior information can improve network inference. However, previous efforts were limited in the types of priors used or have only been applied to model systems. In this study, we reconstruct the regulatory networks underlying trans-QTL hotspots using human cohort data and data-driven prior information. METHODS: We devised a new strategy to integrate QTL with human population scale multi-omics data. State-of-the art network inference methods including BDgraph and glasso were applied to these data. Comprehensive prior information to guide network inference was manually curated from large-scale biological databases. The inference approach was extensively benchmarked using simulated data and cross-cohort replication analyses. Best performing methods were subsequently applied to real-world human cohort data. RESULTS: Our benchmarks showed that prior-based strategies outperform methods without prior information in simulated data and show better replication across datasets. Application of our approach to human cohort data highlighted two novel regulatory networks related to schizophrenia and lean body mass for which we generated novel functional hypotheses. CONCLUSIONS: We demonstrate that existing biological knowledge can improve the integrative analysis of networks underlying trans associations and generate novel hypotheses about regulatory mechanisms

Altered metabolic landscape in IDH‐mutant gliomas affects phospholipid, energy, and oxidative stress pathways

Heterozygous mutations in NADP‐dependent isocitrate dehydrogenases (IDH) define the large majority of diffuse gliomas and are associated with hypermethylation of DNA and chromatin. The metabolic dysregulations imposed by these mutations, whether dependent or not on the oncometabolite D‐2‐hydroxyglutarate (D2HG), are less well understood. Here, we applied mass spectrometry imaging on intracranial patient‐derived xenografts of IDH‐mutant versus IDH wild‐type glioma to profile the distribution of metabolites at high anatomical resolution in situ. This approach was complemented by in vivo tracing of labeled nutrients followed by liquid chromatography–mass spectrometry (LC‐MS) analysis. Selected metabolites were verified on clinical specimen. Our data identify remarkable differences in the phospholipid composition of gliomas harboring the IDH1 mutation. Moreover, we show that these tumors are characterized by reduced glucose turnover and a lower energy potential, correlating with their reduced aggressivity. Despite these differences, our data also show that D2HG overproduction does not result in a global aberration of the central carbon metabolism, indicating strong adaptive mechanisms at hand. Intriguingly, D2HG shows no quantitatively important glucose‐derived label in IDH‐mutant tumors, which suggests that the synthesis of this oncometabolite may rely on alternative carbon sources. Despite a reduction in NADPH, glutathione levels are maintained. We found that genes coding for key enzymes in de novo glutathione synthesis are highly expressed in IDH‐mutant gliomas and the expression of cystathionine‐β‐synthase (CBS) correlates with patient survival in the oligodendroglial subtype. This study provides a detailed and clinically relevant insight into the in vivo metabolism of IDH1‐mutant gliomas and points to novel metabolic vulnerabilities in these tumors

Strong microsite control of seedling recruitment in tundra

The inclusion of environmental variation in studies of recruitment is a prerequisite for realistic predictions of the responses of vegetation to a changing environment. We investigated how seedling recruitment is affected by seed availability and microsite quality along a steep environmental gradient in dry tundra. A survey of natural seed rain and seedling density in vegetation was combined with observations of the establishment of 14 species after sowing into intact or disturbed vegetation. Although seed rain density was closely correlated with natural seedling establishment, the experimental seed addition showed that the microsite environment was even more important. For all species, seedling emergence peaked at the productive end of the gradient, irrespective of the adult niches realized. Disturbance promoted recruitment at all positions along the environmental gradient, not just at high productivity. Early seedling emergence constituted the main temporal bottleneck in recruitment for all species. Surprisingly, winter mortality was highest at what appeared to be the most benign end of the gradient. The results highlight that seedling recruitment patterns are largely determined by the earliest stages in seedling emergence, which again are closely linked to microsite quality. A fuller understanding of microsite effects on recruitment with implications for plant community assembly and vegetation change is provided

Skin and Soft Tissue Infections Caused by Methicillin-Resistant Staphylococcus aureus USA300 Clone

An increase in SSTIs suggests that USA300 is becoming more virulent with a greater propensity to cause SSTIs

The impact of language co-activation on L1 and L2 speech fluency

Fluent speech depends on the availability of well-established linguistic knowledge and routines for speech planning and articulation. A lack of speech fluency in late second-language (L2) learners may point to a deficiency of these representations, due to incomplete acquisition. Experiments on bilingual language processing have shown, however, that there are strong reasons to believe that multilingual speakers experience co-activation of the languages they speak. We have studied to what degree language co-activation affects fluency in the speech of bilinguals, comparing a monolingual German control group with two bilingual groups: 1) first-language (L1) attriters, who have fully acquired German before emigrating to an L2 English environment, and 2) immersed L2 learners of German (L1: English). We have analysed the temporal fluency and the incidence of disfluency markers (pauses, repetitions and self-corrections) in spontaneous film retellings. Our findings show that learners to speak more slowly than controls and attriters. Also, on each count, the speech of at least one of the bilingual groups contains more disfluency markers than the retellings of the control group. Generally speaking, both bilingual groups-learners and attriters-are equally (dis)fluent and significantly more disfluent than the monolingual speakers. Given that the L1 attriters are unaffected by incomplete acquisition, we interpret these findings as evidence for language competition during speech production

Beyond the conflict: religion in the public sphere and deliberative democracy

Traditionally, liberals have confined religion to the sphere of the ‘private’ or ‘non-political’. However, recent debates over the use of religious symbols in public spaces, state financing of faith schools, and tax relief for religious organisations suggest that this distinction is not particularly useful in easing the tension between liberal ideas of equality among citizens and freedom of religion. This article deals with one aspect of this debate, which concerns whether members of religious communities should receive exemptions from regulations that place a distinctively heavy burden on them. For supporters of exemptions, protection for diverse practices and religious beliefs justifies such a special treatment. For others, this is a form of positive discrimination incompatible with equal citizenship. Drawing on Habermas’ understanding of churches as ‘communities of interpretation’ this article explores possible alternative solutions to both the ‘rule-andexemption’ approach and the ‘neutralist’ approach. Our proposal rests on the idea of mutual learning between secular and religious perspectives. On this interpretation, what is required is, firstly, generation and maintenance of public spaces in which there could be discussion and dialogue about particular cases, and, secondly, evaluation of whether the basic conditions of moral discourse are present in these spaces. Thus deliberation becomes a touchstone for the building of a shared democratic etho

Financial Self-Help Associations among Far West Nepalese Labor Migrants in Delhi, India

Labor migration to India is the most important source of income for people in Far West Nepal. To better understand the effects of labor migration, a research analyzing why and how migrants invest their money in financial self-help organizations was undertaken. Fieldwork was conducted in the communities of origin in Nepal and migrant communities in India. Based on the study, the paper provides an overview of the existing financial self-help associations, their strengths and weaknesses, accessibility and possibilities of benefits and losses for the migrants and their families. The major conclusion is that migration helps to improve income or security but can also undermine a household's financial situation by perpetuating debt and dependency