Practice links [Issue 59, October 2014]

Practice Links is a free e-publication for practitioners working in Irish social services, voluntary and nongovernmental sectors. Practice Links was created to enable practitioners to keep up-to-date with new publications, electronic resources and conference opportunities. Issue 59 includes listings for upcoming conferences, podcast listings, information resources, recent policy reports as well as reviews of publications.

Co-regulation of nuclear respiratory factor-1 by NFkappaB and CREB links LPS-induced inflammation to mitochondrial biogenesis.

The nuclear respiratory factor-1 (NRF1) gene is activated by lipopolysaccharide (LPS), which might reflect TLR4-mediated mitigation of cellular inflammatory damage via initiation of mitochondrial biogenesis. To test this hypothesis, we examined NRF1 promoter regulation by NFκB, and identified interspecies-conserved κB-responsive promoter and intronic elements in the NRF1 locus. In mice, activation of Nrf1 and its downstream target, Tfam, by Escherichia coli was contingent on NFκB, and in LPS-treated hepatocytes, NFκB served as an NRF1 enhancer element in conjunction with NFκB promoter binding. Unexpectedly, optimal NRF1 promoter activity after LPS also required binding by the energy-state-dependent transcription factor CREB. EMSA and ChIP assays confirmed p65 and CREB binding to the NRF1 promoter and p65 binding to intron 1. Functionality for both transcription factors was validated by gene-knockdown studies. LPS regulation of NRF1 led to mtDNA-encoded gene expression and expansion of mtDNA copy number. In cells expressing plasmid constructs containing the NRF-1 promoter and GFP, LPS-dependent reporter activity was abolished by cis-acting κB-element mutations, and nuclear accumulation of NFκB and CREB demonstrated dependence on mitochondrial H(2)O(2). These findings indicate that TLR4-dependent NFκB and CREB activation co-regulate the NRF1 promoter with NFκB intronic enhancement and redox-regulated nuclear translocation, leading to downstream target-gene expression, and identify NRF-1 as an early-phase component of the host antibacterial defenses.

Terminating links between emission trading programs

© 2015 Elsevier Inc.Links between emission trading programs are not immutable, as highlighted by New Jersey's exit from the Regional Greenhouse Gas Initiative in 2011. This raises the question of what to do with existing permits that are banked for future use-choices that have consequences for market behavior in advance of, or upon speculation about, delinking. We consider two delinking policies. One differentiates banked permits by origin, the other treats banked permits the same. We describe the price behavior and relative cost-effectiveness of each policy. Treating permits differently generally leads to higher costs, and may lead to price divergence, even with only speculation about delinking.

Statistical analysis of crystallization database links protein physico-chemical features with crystallization mechanisms.

X-ray crystallography is the predominant method for obtaining atomic-scale information about biological macromolecules. Despite the success of the technique, obtaining well diffracting crystals still critically limits going from protein to structure. In practice, the crystallization process proceeds through knowledge-informed empiricism. Better physico-chemical understanding remains elusive because of the large number of variables involved, hence little guidance is available to systematically identify solution conditions that promote crystallization. To help determine relationships between macromolecular properties and their crystallization propensity, we have trained statistical models on samples for 182 proteins supplied by the Northeast Structural Genomics consortium. Gaussian processes, which capture trends beyond the reach of linear statistical models, distinguish between two main physico-chemical mechanisms driving crystallization. One is characterized by low levels of side chain entropy and has been extensively reported in the literature. The other identifies specific electrostatic interactions not previously described in the crystallization context. Because evidence for two distinct mechanisms can be gleaned both from crystal contacts and from solution conditions leading to successful crystallization, the model offers future avenues for optimizing crystallization screens based on partial structural information. The availability of crystallization data coupled with structural outcomes analyzed through state-of-the-art statistical models may thus guide macromolecular crystallization toward a more rational basis.

CPAG: software for leveraging pleiotropy in GWAS to reveal similarity between human traits links plasma fatty acids and intestinal inflammation.

Meta-analyses of genome-wide association studies (GWAS) have demonstrated that the same genetic variants can be associated with multiple diseases and other complex traits. We present software called CPAG (Cross-Phenotype Analysis of GWAS) to look for similarities between 700 traits, build trees with informative clusters, and highlight underlying pathways. Clusters are consistent with pre-defined groups and literature-based validation but also reveal novel connections. We report similarity between plasma palmitoleic acid and Crohn's disease and find that specific fatty acids exacerbate enterocolitis in zebrafish. CPAG will become increasingly powerful as more genetic variants are uncovered, leading to a deeper understanding of complex traits. CPAG is freely available at www.sourceforge.net/projects/CPAG/.

Strong links between phytoplankton community physiology and dimethylsulphoniopropionate (DMSP) concentrations in the sub-tropical/tropical Atlantic

We present an extensive dataset of dimethylsulphide (DMS, n = 651) and dimethylsulphoniopropionate (DMSP, n = 590) from the Atlantic Meridional Transect programme. These data are used to derive representative depth profiles that illustrate observed natural variations and can be used for DMS and DMSP model-validation in oligotrophic waters. To further understand our dataset, we interpret the data with a wide range of accompanying parameters that characterise the prevailing biogeochemical conditions and phytoplankton community physiology, activity, taxonomic composition, and capacity to cope with light stress. No correlations were observed with typical biomarker pigments for DMSP-producing species. However, strong correlations were found between DMSP and primary production by cells >2 µm in diameter, and between DMSP and some photo-protective pigments. These parameters are measures of mixed phytoplankton communities, so we infer that such associations are likely to be stronger in DMSP-producing organisms. Further work is warranted to develop links between community parameters, DMS and DMSP at the global scale.

La justificación del Derecho de Resistencia en el Estado Constitucional Democrático de Derecho: algunas reflexiones iusfilosóficas

This paper aims to demonstrate how in the constitutional rule of law the right of resistance plays a key role in its development, its adaptation to the changing reality of society and the satisfaction of the interests of all the people involved in this common project. Firstly, we will analyze how individuals or social groups must act when they suffer injustices due to state acts or laws that violate their most basic rights. In some cases, we believe that they have the right to exercise any form of weak resistance that they deem appropriate to present at the public scene a cause that must be socially and politically recognized. Secondly, we will see what happens when the rule of law itself is in danger. In that case, we believe that society will have not only the right but the duty to exercise the resistance in its most extreme form to defend the existing constitutional order of any illegitimate authority that seeks to impose itself on it and the sovereignty of the people.