Analysis of IL2/IL21 Gene Variants in Cholestatic Liver Diseases Reveals an Association with Primary Sclerosing Cholangitis

Background/Aims: The chromosome 4q27 region harboring IL2 and IL21 is an established risk locus for ulcerative colitis (UC) and various other autoimmune diseases. Considering the strong coincidence of primary sclerosing cholangitis (PSC) with UC and the increased frequency of other autoimmune disorders in patients with primary biliary cirrhosis (PBC), we investigated whether genetic variation in the IL2/IL21 region may also modulate the susceptibility to these two rare cholestatic liver diseases. Methods: Four strongly UC-associated single nucleotide polymorphisms (SNPs) within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block were genotyped in 124 PBC and 41 PSC patients. Control allele frequencies from 1,487 healthy, unrelated Caucasians were available from a previous UC association study. Results: The minor alleles of all four markers were associated with a decreased susceptibility to PSC (rs13151961: p = 0.013, odds ratio (OR) 0.34; rs13119723: p = 0.023, OR 0.40; rs6822844: p = 0.031, OR 0.41; rs6840978: p = 0.043, OR 0.46). Moreover, a haplotype consisting of the four minor alleles also had a protective effect on PSC susceptibility (p = 0.0084, OR 0.28). A haplotype of the four major alleles was independently associated with PSC when excluding the patients with concomitant inflammatory bowel disease (p = 0.033, OR 4.18). Conclusion: The IL2/IL21 region may be one of the highly suggestive but so far rarely identified shared susceptibility loci for PSC and UC. Copyright (C) 2011 S. Karger AG, Base

Glucocorticoid Nanoparticles Show Full Therapeutic Efficacy in a Mouse Model of Acute Lung Injury and Concomitantly Reduce Adverse Effects.

Glucocorticoids (GCs) are widely used to treat inflammatory disorders such as acute lung injury (ALI). Here, we explored inorganic-organic hybrid nanoparticles (IOH-NPs) as a new delivery vehicle for GCs in a mouse model of ALI. Betamethasone (BMZ) encapsulated into IOH-NPs (BNPs) ameliorated the massive infiltration of neutrophils into the airways with a similar efficacy as the free drug. This was accompanied by a potent inhibition of pulmonary gene expression and secretion of pro-inflammatory mediators, whereas the alveolar-capillary barrier integrity was only restored by BMZ in its traditional form. Experiments with genetically engineered mice identified myeloid cells and alveolar type II (AT II) cells as essential targets of BNPs in ALI therapy, confirming their high cell-type specificity. Consequently, adverse effects were reduced when using IOH-NPs for GC delivery. BNPs did not alter T and B cell numbers in the blood and also prevented the induction of muscle atrophy after three days of treatment. Collectively, our data suggest that IOH-NPs target GCs to myeloid and AT II cells, resulting in full therapeutic efficacy in the treatment of ALI while being associated with reduced adverse effects

The life cycle impact for platinum group metals and lithium to 2070 via surplus cost potential

© 2017 The Author(s)Purpose: A surplus cost potential (SCP) indicator has been developed as a measure of resource scarcity in the life cycle impact assessment (LCIA) context. To date, quality SCP estimates for other minerals than fossils are either not yet available or suffer methodological and data limitations. This paper overcomes these limitations and demonstrate how SCP estimates for metals can be calculated without the utilisation of ore grade function and by collecting primary economic and geological data. Methods: Data were collected in line with the geographical distribution, mine type, deposit type and production volumes and total production costs in order to construct cost-cumulative availability curves for platinum group metals (PGMs) and lithium. These curves capture the total amount of known mineral resources that can be recovered profitably at various prices from different types of mineral deposits under current conditions (this is, current technology, prevailing labour and other input prices). They served as a basis for modelling the marginal cost increase, a necessary parameter for estimating the SCP indicator. Surplus costs were calculated for different scenario projections for future mineral production considering future market dynamics, recyclability rates, demand-side technological developments and economic growth and by applying declining social discount rate. Results and discussion: Surplus costs were calculated for three mineral production scenarios, ranging from (US$2014/kg) 6545–8354 for platinum, 3583–4573 for palladium, 8281–10,569 for rhodium, 513–655 for ruthenium, 3201–4086 for iridium and 1.70–5.80 for lithium. Compared with the current production costs, the results indicate that problematic price increases of lithium are unlikely if the latest technological trends in the automotive sector will continue up to 2070. Surplus costs for PGMs are approximately one-third of the current production costs in all scenarios; hence, a threat of their price increases by 2070 will largely depend on the discovery of new deposits and the ability of new technologies to push these costs down over time. This also applies to lithium if the increasing electrification of road transport will continue up to 2070. Conclusions: This study provides useful insight into the availability of PGMs and lithium up to 2070. It proves that if time and resources permit, reliable surplus cost estimates can be calculated, at least in the short-run, based on the construction of one’s own curves with the level of quality comparable to expert-driven consulting services. Modelling and incorporating unknown deposits and potential future mineral production costs into these curves is the subject of future work

The comparative osmoregulatory ability of two water beetle genera whose species span the fresh-hypersaline gradient in inland waters (Coleoptera: Dytiscidae, Hydrophilidae).

A better knowledge of the physiological basis of salinity tolerance is essential to understanding the ecology and evolutionary history of organisms that have colonized inland saline waters. Coleoptera are amongst the most diverse macroinvertebrates in inland waters, including saline habitats; however, the osmoregulatory strategies they employ to deal with osmotic stress remain unexplored. Survival and haemolymph osmotic concentration at different salinities were examined in adults of eight aquatic beetle species which inhabit different parts of the fresh-hypersaline gradient. Studied species belong to two unrelated genera which have invaded saline waters independently from freshwater ancestors; Nebrioporus (Dytiscidae) and Enochrus (Hydrophilidae). Their osmoregulatory strategy (osmoconformity or osmoregulation) was identified and osmotic capacity (the osmotic gradient between the animal's haemolymph and the external medium) was compared between species pairs co-habiting similar salinities in nature. We show that osmoregulatory capacity, rather than osmoconformity, has evolved independently in these different lineages. All species hyperegulated their haemolymph osmotic concentration in diluted waters; those living in fresh or low-salinity waters were unable to hyporegulate and survive in hyperosmotic media (> 340 mosmol kg(-1)). In contrast, the species which inhabit the hypo-hypersaline habitats were effective hyporegulators, maintaining their haemolymph osmolality within narrow limits (ca. 300 mosmol kg(-1)) across a wide range of external concentrations. The hypersaline species N. ceresyi and E. jesusarribasi tolerated conductivities up to 140 and 180 mS cm(-1), respectively, and maintained osmotic gradients over 3500 mosmol kg(-1), comparable to those of the most effective insect osmoregulators known to date. Syntopic species of both genera showed similar osmotic capacities and in general, osmotic responses correlated well with upper salinity levels occupied by individual species in nature. Therefore, osmoregulatory capacity may mediate habitat segregation amongst congeners across the salinity gradient

Comparative transcriptomic analysis reveals similarities and dissimilarities in saccharomyces cerevisiae wine strains response to nitrogen availability

Nitrogen levels in grape-juices are of major importance in winemaking ensuring adequate yeast growth and fermentation performance. Here we used a comparative transcriptome analysis to uncover wine yeasts responses to nitrogen availability during fermentation. Gene expression was assessed in three genetically and phenotypically divergent commercial wine strains (CEG, VL1 and QA23), under low (67 mg/L) and high nitrogen (670 mg/L) regimes, at three time points during fermentation (12h, 24h and 96h). Two-way ANOVA analysis of each fermentation condition led to the identification of genes whose expression was dependent on strain, fermentation stage and on the interaction of both factors. The high fermenter yeast strain QA23 was more clearly distinct from the other two strains, by differential expression of genes involved in flocculation, mitochondrial functions, energy generation and protein folding and stabilization. For all strains, higher transcriptional variability due to fermentation stage was seen in the high nitrogen fermentations. A positive correlation between maximum fermentation rate and the expression of genes involved in stress response was observed. The finding of common genes correlated with both fermentation activity and nitrogen up-take underlies the role of nitrogen on yeast fermentative fitness. The comparative analysis of genes differentially expressed between both fermentation conditions at 12h, where the main difference was the level of nitrogen available, showed the highest variability amongst strains revealing strain-specific responses. Nevertheless, we were able to identify a small set of genes whose expression profiles can quantitatively assess the common response of the yeast strains to varying nitrogen conditions. The use of three contrasting yeast strains in gene expression analysis prompts the identification of more reliable, accurate and reproducible biomarkers that will facilitate the diagnosis of deficiency of this nutrient in the grape-musts and the development of strategies to optimize yeast performance in industrial fermentations

Rasiowa–Sikorski deduction systems in computer science applications

AbstractA Rasiowa-Sikorski system is a sequence-type formalization of logics. The system uses invertible decomposition rules which decompose a formula into sequences of simpler formulae whose validity is equivalent to validity of the original formula. There may also be expansion rules which close indecomposable sequences under certain properties of relations appearing in the formulae, like symmetry or transitivity. Proofs are finite decomposition trees with leaves having “fundamental”, valid labels. The author describes a general method of applying the R-S formalism to develop complete deduction systems for various brands of C.S and A.I. logic, including a logic for reasoning about relative similarity, a three-valued software specification logic with McCarthy's connectives and Kleene quantifiers, a logic for nondeterministic specifications, many-sorted FOL with possibly empty carriers of some sorts, and a three-valued logic for reasoning about concurrency

The TRAF1/C5 region is a risk factor for polyarthritis in juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a chronic disorder in which both genetic and environmental factors are involved. Recently, we identified the TRAF1/C5 region (located on chromosome 9q33-34) as a risk factor for rheumatoid arthritis (RA) (p(combined) = 1.4 x 10(-8)). In the present study the association of the TRAF1/C5 region with the susceptibility to JIA was investigated. A case-control association study was performed in 338 Caucasian patients with JIA and 511 healthy individuals. We genotyped the single nucleotide polymorphism rs10818488 as a marker for the TRAF1/C5 region. The A allele was associated with the susceptibility to rheumatoid factor-negative polyarthritis with an 11% increase in allele frequency (OR 1.54, 95% CI 1.09 to 2.18; p = 0.012). This association was stronger when combining subtypes with a polyarticular phenotype (OR 1.46, 95% CI 1.12 to 1.90; p = 0.004). In addition, we observed a trend towards an increase in A allele frequency in patients with extended oligoarthritis versus persistent oligoarthritis (49%, 38% respectively); p = 0.055. Apart from being a well replicated risk factor for RA, TRAF1/C5 also appears to be a risk factor for the rheumatoid factor-negative polyarthritis subtype of JIA and, more generally, seems to be associated with subtypes of JIA characterised by a polyarticular cours

Association of the CD226 (DNAM-1) Gly307Ser polymorphism with juvenile idiopathic arthritis

No abstract available

Association of the CCR5Δ32 variant with juvenile idiopathic arthritis in a meta-analysis

No abstract available