Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis

Antibodies to citrullinated proteins (anti-cyclic-citrullinated peptide [anti-CCP] antibodies) are highly specific for rheumatoid arthritis (RA) and precede the onset of disease symptoms, indicating a pathogenetic role for these antibodies in RA. We recently showed that distinct genetic risk factors are associated with either anti-CCP-positive disease or anti-CCP-negative disease. These data are important as they indicate that distinct pathogenic mechanisms are underlying anti-CCP-positive disease or anti-CCP-negative disease. Likewise, these observations raise the question of whether anti-CCP-positive RA and anti-CCP-negative RA are clinically different disease entities. We therefore investigated whether RA patients with anti-CCP antibodies have a different clinical presentation and disease course compared with patients without these autoantibodies. In a cohort of 454 incident patients with RA, 228 patients were anti-CCP-positive and 226 patients were anti-CCP-negative. The early symptoms, tender and swollen joint count, and C-reactive protein level at inclusion, as well as the swollen joint count and radiological destruction during 4 years of follow-up, were compared for the two groups. There were no differences in morning stiffness, type, location and distribution of early symptoms, patients' rated disease activity and C-reactive protein at inclusion between RA patients with and without anti-CCP antibodies. The mean tender and swollen joint count for the different joints at inclusion was similar. At follow-up, patients with anti-CCP antibodies had more swollen joints and more severe radiological destruction. Nevertheless, the distribution of affected joints, for swelling, bone erosions and joint space narrowing, was similar. In conclusion, the phenotype of RA patients with or without anti-CCP antibodies is similar with respect to clinical presentation but differs with respect to disease course.     

A completely foreign receptor can mediate an interferon-gamma-like response

A tripartite receptor comprising the external region of the erythropoietin (Epo) receptor, the transmembrane and JAK-binding domains of the gp130 subunit of the interleukin-6 (IL-6) receptor, and a seven amino acid STAT1 recruitment motif (Y440) from the interferon (IFN)-gamma receptor, efficiently mediates an IFN-gamma-like response. An analogous completely foreign chimeric receptor in which the Y440 motif is replaced with the Y905 motif from gp130 also mediates an IFN-gamma-like response, but less efficiently. The IFNGR1 signal-transducing subunit of the IFN-gamma receptor is tyrosine phosphorylated through the chimeric receptors and the endogenous IL-6 and OSM receptors. Cross phosphorylation of IFNGR1 is not, however, required for the IFN-gamma-like response through the chimeric receptors, nor does it mediate an IFN-gamma-like response to IL-6 or OSM. The data argue strongly for modular JAK/STAT signalling and against any rigid structural organization for the "pathways" involved. They emphasize the likely high degree of overlap between the signals generated from disparate JAK-receptor complexes and show that relatively minor changes in such complexes can profoundly affect the response.     

Design of reference populations for genomic selection in crossbreeding programs

Background

In crossbreeding programs, genomic selection offers the opportunity to make efficient use of information on crossbred (CB) individuals in the selection of purebred (PB) candidates. In such programs, reference populations often contain genotyped PB animals, although the breeding objective is usually more focused on CB performance. The question is what would be the benefit of including a larger proportion of CB individuals in the reference population.

Methods

In a deterministic simulation study, we evaluated the benefit of including various proportions of CB animals in a reference population for genomic selection of PB animals in a crossbreeding program. We used a pig breeding scheme with selection for a moderately heritable trait and a size of 6000 for the reference population.

Results

Applying genomic selection to improve the performance of CB individuals, with a genetic correlation between PB and CB performance (r_PC) of 0.7, selection accuracy of PB candidates increased from 0.49 to 0.52 if the reference population consisted of PB individuals, it increased to 0.55 if the reference population consisted of the same number of CB individuals, and to 0.60 if the size of the CB reference population was twice that of the reference population for each PB line. The advantage of using CB rather than PB individuals increased linearly with the proportion of CB individuals in the reference population. This advantage disappeared quickly if r_PC was higher or if the breeding objective put some emphasis on PB performance. The benefit of adding CB individuals to an existing PB reference population was limited for high r_PC.

Conclusions

Using CB rather than PB individuals in a reference population for genomic selection can provide substantial advantages, but only when correlations between PB and CB performances are not high and PB performance is not part of the breeding objective.     

Meta‐analysis reveals the importance of matrix composition for animals in fragmented habitat

Aim Connectivity is a key determinant of the distribution and abundance of organisms and is greatly influenced by anthropogenic landscape modification, yet we lack a synthetic perspective on the magnitude and extent of matrix effects on connectivity. We synthesize results from published studies to understand the importance of matrix effects on fragmented animal populations. Location Global. Methods We conduct a meta‐analysis of 283 fragmented populations representing 184 terrestrial animal taxa to determine the strength of matrix composition effects on the occurrence and abundance of animals in fragmented habitat. Results Studies that use data on matrix composition report greater effects on abundance and occupancy of fragmented populations than studies that define connectivity without regard to the surrounding matrix (i.e. ‘binary’ studies that describe only characteristics of patch habitat). Main conclusions Our findings underscore that conservation strategies must consider the importance of matrix habitat, have important implications for metapopulation and metacommunity paradigms, and provide direct large‐scale, multi‐taxa evidence that matrix habitat is an important driver of ecological dynamics in heterogeneous landscapes.     

Larger fungi around Kindrogan,Perthshire

Summary

540 agarics and 156 other basidiomycetes, (excluding rusts and smuts), are recorded for an area within a 40 km radius of the Kindrogan Field Centre, Perthshire. Several are new records and do not appear in checklists for the British Isles; notes are provided on new, interesting and rare species.     

Addendum

Summary

A survey of South Craigroston Wood shows a range of tree densities from ?200 to? 1000 trees/ha with dominant oak and birch but with an increased representation of alder in wetter areas. The size distribution of oaks may be tentatively related to previous management. The ground flora can be divided into a major grouping associated with drier, acidic sites with a high incidence of oak and minor, species-rich, groupings associated with damper and more base-rich sites with greater proportions of alder, ash and hazel. The ground flora is much less diverse than that described from the island of Inchcailloch.     

Molecular insights into Cumacean family relationships (Crustacea, Cumacea)

Cumaceans are a diverse order of small, benthic marine crustaceans. Phylogenetic hypotheses for the eight currently recognized cumacean families have not been formally proposed. However, based on external morphological traits and Linnean classification, a few conflicting hypotheses of relatedness have been proposed. Family definitions rely on morphological characters that often overlap and diagnoses are based on a combination of non-unique characters. Morphological analysis does not provide a well-resolved phylogeny. In the present study, we use amino acid sequences from the mitochondrial cytochrome oxidase I gene to produce a molecular phylogenetic hypothesis for the families of Cumacea. Phylogenetic analyses at the amino acid level were performed under Bayesian, likelihood, and parsimony methods. Results strongly suggest that families lacking an articulated telson form a monophyletic group. This pleotelson clade, composed of the families Bodotriidae, Leuconidae, and Nannastacidae, is the most derived within the Cumacea. Within this group, the Bodotriidae resolve paraphyletically, with Leuconidae and Nannastacidae embedded within it. Comparison of the molecular phylogeny with that based on morphology suggests that many "diagnostic" characters are homoplasious.