Unlocking legal validity. Some remarks on the artificial ontology of law

Following Kelsen’s influential theory of law, the concept of validity has been used in the literature to refer to different properties of law (such as existence, membership, bindingness, and more) and so it is inherently ambiguous. More importantly, Kelsen’s equivalence between the existence and the validity of law prevents us from accounting satisfactorily for relevant aspects of our current legal practices, such as the phenomenon of ‘unlawful law’. This chapter addresses this ambiguity to argue that the most important function of the concept of validity is constituting the complex ontological paradigm of modern law as an institutional-normative practice. In this sense validity is an artificial ontological status that supervenes on that of existence of legal norms, thus allowing law to regulate its own creation and creating the logical space for the occurrence of ‘unlawful law’. This function, I argue in the last part, is crucial to understanding the relationship between the ontological and epistemic dimensions of the objectivity of law. For given the necessary practice-independence of legal norms, it is the epistemic accessibility of their creation that enables the law to fulfill its general action-guiding (and thus coordinating) function

LAL Regulators SCO0877 and SCO7173 as Pleiotropic Modulators of Phosphate Starvation Response and Actinorhodin Biosynthesis in Streptomyces coelicolor

LAL regulators (Large ATP-binding regulators of the LuxR family) constitute a poorly studied family of transcriptional regulators. Several regulators of this class have been identified in antibiotic and other secondary metabolite gene clusters from actinomycetes, thus they have been considered pathway-specific regulators. In this study we have obtained two disruption mutants of LAL genes from S. coelicolor (Δ0877 and Δ7173). Both mutants were deficient in the production of the polyketide antibiotic actinorhodin, and antibiotic production was restored upon gene complementation of the mutants. The use of whole-genome DNA microarrays and quantitative PCRs enabled the analysis of the transcriptome of both mutants in comparison with the wild type. Our results indicate that the LAL regulators under study act globally affecting various cellular processes, and amongst them the phosphate starvation response and the biosynthesis of the blue-pigmented antibiotic actinorhodin. Both regulators act as negative modulators of the expression of the two-component phoRP system and as positive regulators of actinorhodin biosynthesis. To our knowledge this is the first characterization of LAL regulators with wide implications in Streptomyces metabolism

Adolescents’ beverage choice at school and the impact on sugar intake

Background/Objectives: To examine students’ beverage choice in school, with reference to its contribution to students’ intake of non-milk extrinsic (NME) sugars. Subjects/Methods: Beverage and food selection data for students aged 11–18 years (n=2461) were collected from two large secondary schools in England, for a continuous period of 145 (school A) and 125 (school B) school days. Descriptive analysis followed by cluster analysis of the beverage data were performed separately for each school. Results: More than a third of all items selected by students were beverages, and juice-based beverages were students’ most popular choice (school A, 38.6%; school B, 35.2%). Mean NME sugars derived from beverages alone was high (school A, 16.7 g/student-day; school B, 12.9 g/student-day). Based on beverage purchases, six clusters of students were identified at each school (school A: ‘juice-based’, ‘assorted’, ‘water’, ‘cartoned flavoured milk’, ‘bottled flavoured milk’, ‘high volume juice-based’; school B: ‘assorted’, ‘water with juice-based’, ‘sparkling juice/juice-based’, ‘water’, ‘high volume water’, ‘high volume juice-based’). Both schools included ‘high volume juice-based’ clusters with the highest NME sugar means from beverages (school A, 28.6 g/student-day; school B, 24.4 g/student-day), and ‘water’ clusters with the lowest. A hierarchy in NME sugars was found according to cluster; students in the ‘high volume juice-based’ cluster returned significantly higher levels of NME sugars than students in other clusters. Conclusions: This study reveals the contribution that school beverages combined with students’ beverage choice behaviour is making to students’ NME sugar intake. These findings inform school food initiatives, and more generally public health policy around adolescents’ dietary intake

Childhood trauma, life-time self-harm, and suicidal behaviour and ideation are associated with polygenic scores for autism

Abstract: Autistic individuals experience significantly elevated rates of childhood trauma, self-harm and suicidal behaviour and ideation (SSBI). Is this purely the result of negative environmental experiences, or does this interact with genetic predisposition? In this study we investigated if a genetic predisposition for autism is associated with childhood trauma using polygenic scores (PGS) and genetic correlations in the UK Biobank (105,222 < N < 105,638), and tested potential mediators and moderators of the association between autism, childhood trauma and SSBI. Autism PGS were significantly associated with childhood trauma (max R2 = 0.096%, P < 2 × 10−16), self-harm ideation (max R2 = 0.108%, P < 2 × 10−16), and self-harm (max R2 = 0.13%, P < 2 × 10−16). Supporting this, we identified significant genetic correlations between autism and childhood trauma (rg = 0.36 ± 0.05, P = 8.13 × 10−11), self-harm ideation (rg = 0.49 ± 0.05, P = 4.17 × 10−21) and self-harm (rg = 0.48 ± 0.05, P = 4.58 × 10−21), and an over-transmission of PGS for the two SSBI phenotypes from parents to autistic probands. Male sex negatively moderated the effect of autism PGS on childhood trauma (β = −0.023 ± 0.005, P = 6.74 × 10−5). Further, childhood trauma positively moderated the effect of autism PGS on self-harm score (β = 8.37 × 10−3 ± 2.76 × 10−3, P = 2.42 × 10−3) and self-harm ideation (β = 7.47 × 10−3 ± 2.76 × 10−3, P = 6.71 × 10−3). Finally, depressive symptoms, quality and frequency of social interactions, and educational attainment were significant mediators of the effect of autism PGS on SSBI, with the proportion of effect mediated ranging from 0.23 (95% CI: 0.09–0.32) for depression to 0.008 (95% CI: 0.004–0.01) for educational attainment. Our findings identify that a genetic predisposition for autism is associated with adverse life-time outcomes, which represent complex gene-environment interactions, and prioritizes potential mediators and moderators of this shared biology. It is important to identify sources of trauma for autistic individuals in order to reduce their occurrence and impact