Sesquiterpene phytoalexins from Ulmus glabra

Inoculation of Wych elm (Ulmus glabra) with the fungi Ceratocystis ulmi, Chrondrostereum purpureum and Coriolus versicolor induced the formation of a series of antifungal cadinane-type sesquiterpenes.     

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.     

The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis

Human ferrochelatase (E.C. 4.99.1.1) is a homodimeric (86 kDa) mitochondrial membrane-associated enzyme that catalyzes the insertion of ferrous iron into protoporphyrin to form heme. We have determined the 2.0 A structure from the single wavelength iron anomalous scattering signal. The enzyme contains two NO-sensitive and uniquely coordinated [2Fe-2S] clusters. Its membrane association is mediated in part by a 12-residue hydrophobic lip that also forms the entrance to the active site pocket. The positioning of highly conserved residues in the active site in conjunction with previous biochemical studies support a catalytic model that may have significance in explaining the enzymatic defects that lead to the human inherited disease erythropoietic protoporphyria.     

Patterning of muscle acetylcholine receptor gene expression in the absence of motor innervation

The patterning of skeletal muscle is thought to depend upon signals provided by motor neurons. We show that AChR gene expression and AChR clusters are concentrated in the central region of embryonic skeletal muscle in the absence of innervation. Neurally derived Agrin is dispensable for this early phase of AChR expression, but MuSK, a receptor tyrosine kinase activated by Agrin, is required to establish this AChR prepattern. The zone of AChR expression in muscle lacking motor axons is wider than normal, indicating that neural signals refine this muscle-autonomous prepattern. Neuronal Neuregulin-1, however, is not involved in this refinement process, nor indeed in synapse-specific AChR gene expression. Our results demonstrate that AChR expression is patterned in the absence of innervation, raising the possibility that similarly prepatterned muscle-derived cues restrict axon growth and initiate synapse formation.     

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.     

Methane indicator values for peatlands: a comparison of species and functional groups

Previous studies have shown a correspondence between the abundance of particular plant species and methane flux. Here, we apply multivariate analyses, and weighted averaging, to assess the suitability of vegetation composition as a predictor of methane flux. We developed a functional classification of the vegetation, in terms of a number of plant traits expected to influence methane production and transport, and compared this with a purely taxonomic classification at species level and higher. We applied weighted averaging and indirect and direct ordination approaches to six sites in the United Kingdom, and found good relationships between methane flux and vegetation composition (classified both taxonomically and functionally). Plant species and functional groups also showed meaningful responses to management and experimental treatments. In addition to the United Kingdom, we applied the functional group classification across different geographical regions (Canada and the Netherlands) to assess the generality of the method. Again, the relationship appeared good at the site level, suggesting some general applicability of the functional classification. The method seems to have the potential for incorporation into large‐scale (national) greenhouse gas accounting programmes (in relation to peatland condition/management) using vegetation mapping schemes. The results presented here strongly suggest that robust predictive models can be derived using plant species data (for use in national‐scale studies). For trans‐national‐scale studies, where the taxonomic assemblage of vegetation differs widely between study sites, a functional classification of plant species data provides an appropriate basis for predictive models of methane flux.