Rabbits (Oryctolagus cuniculus) increase caecal calcium absorption at increasing dietary calcium levels

Hindgut fermenting herbivores from different vertebrate taxa, including tortoises, and among mammals some afrotheria, perissodactyla incl. equids, several rodents as well as lagomorphs absorb more calcium (Ca) from the digesta than they require, and excrete the surplus via urine. Both proximate and ultimate causes are elusive. It was suggested that this mechanism might ensure phosphorus availability for the hindgut microbiome by removing potentially complex‐building Ca from the digesta. Here we use Ussing chamber experiments to show that rabbits (Oryctolagus cuniculus) maintained on four different diets (six animals/diet) increase active Ca absorption at increasing Ca levels. This contradicts the common assumption that at higher dietary levels, where passive uptake should be more prevalent, active transport can relax and hence supports the deliberate removal hypothesis. In the rabbits, this absorption was distinctively higher in the caecum than in the duodenum, which is unexpected in mammals. Additional quantification of the presence of two proteins involved in active Ca absorption (calbindin‐D9K CB; vitamin D receptor, VDR) showed higher presence with higher dietary Ca. However, their detailed distribution across the intestinal tract and the diet groups suggests that other factors not investigated in this study must play major roles in Ca absorption in rabbits. Investigating strategies of herbivores to mitigate potential negative effects of Ca in the digesta on microbial activity and growth might represent a promising area of future research

The incidence of primary glomerulonephritis worldwide:a systematic review of the literature

Background. Little is known about the worldwide variation in incidence of primary glomerulonephritis (GN). The objective of this review was to critically appraise studies of incidence published in 1980-2010 so that an overall view of trends of these diseases can be found. This would provide important information for determining changes in rates and understanding variations between countries. Methods. All relevant papers found through searches of Medline, Embase and ScienceDirect were critically appraised and an assessment was made of the reliability of the reported incidence data. Results. This review includes 40 studies of incidence of primary GN from Europe, North and South America, Canada, Australasia and the Middle East. Rates for the individual types of disease were found to be in adults, 0.2/100 000/year for membrano-proliferative GN, 0.2/100 000/year for mesangio-proliferative GN, 0.6/100 000/year for minimal change disease, 0.8/100 000/year for focal segmental glomerulosclerosis, 1.2/100 000/year for membranous nephropathy and 2.5/100 000/year for IgA nephropathy. Rates were lower in children at around 0.1/100 000/year with the exception of minimal change disease where incidence was reported to be 2.0/100 000/year in Caucasian children with higher rates in Arabian children (9.2/100 000/year) and Asian children (6.2-15.6/100 000/year). Conclusions. This study found that incidence rates of primary GN vary between 0.2/100 000/year and 2.5/100 000/ year. The incidence of IgA nephropathy is at least 2.5/100 000/year in adults; this disease can exist subclinically and is therefore only detected by chance in some patients. In addition, referral policies for diagnostic biopsy vary between countries. This will affect the incidence rates found

Strengthening regulatory science in academia:STARS, an EU initiative to bridge the translational gap

Truly disruptive medicine innovation and new treatment paradigms tend to start in non-commercial research institutions. However, the lack of mutual understanding between medicine developers and regulators when it comes to medicine development significantly delays or even prevents the access of patients to these innovations. Here, we outline what regulatory-related barriers hamper the translational development of novel products or new treatment paradigms initiated in academia, and propose key steps towards improved regulatory dialogue among academia, funding bodies and regulatory authorities. Moreover, we briefly describe how the STARS (Strengthening Training of Academia in Regulatory Science) project aims to reach out to medicine innovators in academia to bridge the regulatory knowledge gap and enhance this dialogue to facilitate the implementation of academic research findings in clinical practice

Genome analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum and Botrytis cinerea

Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic plant pathogenic fungi notable for their wide host ranges and environmental persistence. These attributes have made these species models for understanding the complexity of necrotrophic, broad host-range pathogenicity. Despite their similarities, the two species differ in mating behaviour and the ability to produce asexual spores. We have sequenced the genomes of one strain of S. sclerotiorum and two strains of B. cinerea. The comparative analysis of these genomes relative to one another and to other sequenced fungal genomes is provided here. Their 38–39 Mb genomes include 11,860–14,270 predicted genes, which share 83% amino acid identity on average between the two species. We have mapped the S. sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises transposable elements compared t

Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al