Vitamin D deficiency is associated with higher disease activity and the risk for uveitis in juvenile idiopathic arthritis - data from a German inception cohort

Objective

The objective was to evaluate the 25(OH) vitamin D (25(OH)D) status of patients with juvenile idiopathic arthritis (JIA) and determine whether the 25(OH)D level is associated with disease activity and the course of JIA.

Methods

Patients ≤?16?years of age with recently diagnosed JIA (<?12?months) were enrolled in the inception cohort of patients with newly diagnosed JIA (ICON), an ongoing prospective observational, controlled multicenter study started in 2010. Clinical and laboratory parameters were ascertained quarterly during the first year and half-yearly thereafter.Of the 954 enrolled patients, 360 patients with two blood samples taken during the first 2?years after inclusion and with follow up of 3?years were selected. The serum 25(OH)D levels were determined and compared with those of subjects from the general population after matching for age, sex, migration status and the month of blood-drawing.

Results

Nearly half of the patients had a deficient 25(OH)D level (<?20?ng/ml) in the first serum sample and a quarter had a deficient level in both samples. Disease activity and the risk of developing JIA-associated uveitis were inversely correlated with the 25(OH)D level (β?=???0.20, 95% CI ??0.37; 0.03, hazard ratio 0.95, 95% CI 0.91; 0.99, respectively).

Conclusion

In this study, 25(OH)D deficiency was common and associated with higher disease activity and risk of developing JIA-associated uveitis. Further studies are needed to substantiate these results and determine whether correcting 25(OH)D deficiency is beneficial in JIA.

     

Population genetic structure after 125 years of stocking in sea trout (<Emphasis Type="Italic">Salmo trutta</Emphasis> L.)

Stocking can be an effective management and conservation tool, but it also carries the danger of eroding natural population structure, introducing non-native strains and reducing genetic diversity. Sea trout, the anadromous form of the brown trout (Salmo trutta), is a highly targeted species that is often managed by stocking. Here, we assess the present-day population genetic structure of sea trout in a backdrop of 125 years of stocking in Northern Germany. The study area is characterized by short distances between the Baltic and North Sea river watersheds, historic use of fish from both watersheds for stocking, and the creation of a potential migration corridor between the Baltic and North Sea with the opening of the Kiel Canal 120 years ago. A survey of 24 river systems with 180 SNPs indicates that moderate but highly significant population genetic structure has persisted both within and between the Baltic and North Sea. This genetic structure is characterized by (i) heterogeneous patterns of admixture between the Baltic and North Sea that do not correlate with distance from the Kiel Canal and are therefore likely due to historic stocking practises, (ii) genetic isolation by distance in the Baltic Sea at a spatial scale of <?200 km that is consistent with the homing behaviour of sea trout, and (iii) at least one genetically distinct Baltic Sea river system. In light of these results, we recommend keeping fish of North Sea and Baltic Sea origin separate for stocking, and restricting Baltic Sea translocations to neighbouring river systems.     

Proteomic distinction of renal oncocytomas and chromophobe renal cell carcinomas

Background

Renal oncocytomas (ROs) are benign epithelial tumors of the kidney whereas chromophobe renal cell carcinoma (chRCCs) are malignant renal tumors. The latter constitute 5–7% of renal neoplasias. ROs and chRCCs show pronounced molecular and histological similarities, which renders their differentiation demanding. We aimed for the differential proteome profiling of ROs and early-stage chRCCs in order to better understand distinguishing protein patterns.

Methods

We employed formalin-fixed, paraffin-embedded samples (six RO cases, six chRCC cases) together with isotopic triplex dimethylation and a pooled reference standard to enable cohort-wide quantitative comparison. For lysosomal-associated membrane protein 1 (LAMP1) and integrin alpha-V (ITGAV) we performed corroborative immunohistochemistry (IHC) in an extended cohort of 42 RO cases and 31 chRCC cases.

Results

At 1% false discovery rate, we identified?>?3900 proteins, of which?>?2400 proteins were consistently quantified in at least four RO and four chRCC cases. The proteomic expression profiling discriminated ROs and chRCCs and highlighted established features such as accumulation of mitochondrial proteins in ROs together with emphasizing the accumulation of endo-lysosomal proteins in chRCCs. In line with the proteomic data, IHC showed enrichment of LAMP1 in chRCC and of ITGAV in RO.

Conclusion

We present one of the first differential proteome profiling studies on ROs and chRCCs and highlight differential abundance of LAMP1 and ITGAV in these renal tumors.

     

Polyploid speciation across a suture zone: phylogeography and species delimitation in S French <Emphasis Type="Italic">Leucanthemum</Emphasis> Mill. representatives (Compositae–Anthemideae)

Chromosome counts suggest that the three varieties of the SE French and NW Italian Leucanthemum vulgare subsp. glaucophyllum (var. glaucophyllum: decaploid; var. esterellense: octoploid; var. subglaucum: hexaploid) deserve acknowledgement as independent species. Here we use AFLP fingerprinting and sequence information from two chloroplast regions (psbA-trnH, rpl16) to gain insight into the evolutionary relationships among those species, along with those with the co-occurring and ecologically similar L. pallens (hexaploid) and the closely related L. ircutianum subsp. leucolepis (tetraploid). Both genetic marker systems reveal a geographical differentiation pattern in L. pallens with the Rhône valley forming a suture zone between the western (SW France, Spain) and eastern (SE France, NW Italy) populations, arguing for the existence of two lineages in the species that may have survived the Last Glacial Maximum (LGM) in refugia on the Iberian and Apennine Peninsulas. Transgressions of this suture zone are observable in the case of the hexaploid L. subglaucum from the Massif Central, which shows genetic relationships to the more eastern decaploid L. glaucophyllum from the Alps Maritimes, and the octoploid L. esterellense from the Esterel Massif (Côte d´Azur), for which relationships to the more western populations of the hexaploids L. pallens and L. subglaucum are observable. The genetic and cytological survey of a mixed stand of L. pallens and L. glaucophyllum on Monte Bignone (Liguria, NW Italy) reveals patterns of recent hybridisation of these two species with intermediate octoploid and nonaploid cytotypes that are, however, genetically distinct from L. esterellense.     

Teaching an old pET new tricks: tuning of inclusion body formation and properties by a mixed feed system in E. coli

Applied Microbiology and Biotechnology - Against the outdated belief that inclusion bodies (IBs) in Escherichia coli are only inactive aggregates of misfolded protein, and thus should be avoided...     

Elevated pCO2 affects the lactate metabolic shift in CHO cell culture processes

The shift from lactate production to consumption in CHO cell metabolism is a key event during cell culture cultivations and is connected to increased culture longevity and final product titers. However, the mechanisms controlling this metabolic shift are not yet fully understood. Variations in lactate metabolism have been mainly reported to be induced by process pH and availability of substrates like glucose and glutamine. The aim of this study was to investigate the effects of elevated pCO₂ concentrations on the lactate metabolic shift phenomena in CHO cell culture processes. In this publication, we show that at elevated pCO₂ in batch and fed‐batch cultures, the lactate metabolic shift was absent in comparison to control cultures at lower pCO₂ values. Furthermore, through metabolic flux analysis we found a link between the lactate metabolic shift and the ratio of NADH producing and regenerating intracellular pathways. This ratio was mainly affected by a reduced oxidative capacity of cultures at elevated pCO₂. The presented results are especially interesting for large‐scale and perfusion processes where increased pCO₂ concentrations are likely to occur. Our results suggest, that so far unexplained metabolic changes may be connected to increased pCO₂ accumulation in larger scale fermentations. Finally, we propose several mechanisms through which increased pCO₂ might affect the cell metabolism and briefly discuss methods to enable the lactate metabolic shift during cell cultivations.     

Overcoming Microstructural Limitations in Water Processed Organic Solar Cells by Engineering Customized Nanoparticulate Inks

The application of conjugated polymer and fullerene water‐based nanoparticles (NP) as ecofriendly inks for organic photovoltaics (OPVs) is reported. A low bandgap polymer diketopyrrolopyrrole–quinquethiophene (PDPP5T‐2) and the methanofullerene PC₇₁BM are processed into three types of nanoparticles: pristine fullerene NPs, pristine polymer NPs, and mixed polymer:fullerene NPs, allowing the formation of bulk heterojunction (BHJ) composites with different domain sizes. Mild thermal annealing is required to melt the nanospheres and enable the formation of interconnected pathways within mixed phases. This BHJ is accompanied by a shrinkage of film, whereas the more compact layers show enhanced mobility. Consistently reduced recombination and better performance are found for mixed NP, containing both, the polymer and the fullerene within a single NP. The optimized solar cell processed by ultrasmall NPs delivers a power conversion efficiency of about 3.4%. This is among the highest values reported for aqueous processed OPVs but still lacks performance compared to those being processed from halogenated solvents. Incomplete crystallization is identified as the main root for reduced efficiency. It is nevertheless believed that postprocessing does not cut attraction from printing aqueous organic NP inks as a trendsetting strategy for the reliable and ecofriendly production of organic solar cells.