Microbial colonization drives lymphocyte accumulation and differentiation in the follicle-associated epithelium of Peyer's patches

Peyer's patches (PPs) are lined by follicle-associated epithelium (FAE) with Ag-transporting M cells. To investigate the spatial relationships of B cells, T cells, and dendritic cells (DCs) in PPs during microbial colonization, their in situ redistribution was examined in germfree (GF) rats exposed to a conventional pathogen-free microflora (conventionalized, CV). Although occasional B and T cells occurred in the FAE of GF rats, it contained mainly immature DCs (CD4(+)CD86(-)), whereas mature DCs (CD86(high)) were seen in the interfollicular zones even under GF conditions. In CV rats, DCs had disappeared from the FAE, which instead contained clusters by B and T cells associated with induction of putative M cell pockets. CD86 was seen neither in the FAE nor in the follicles under GF conditions, but it became apparent on intraepithelial B cells 5 wk after colonization. The level of CD86 on these B cells was comparable to that on germinal center B cells, although the B cell follicles did not show direct contact with the M cell areas. B cells in the follicular mantles acquired Bcl-2 after 12 wk in CV rats, whereas B cells in the FAE did not express Bcl-2 at a substantial level throughout the experimental period. The cellular redistribution patterns and phenotypic characteristics observed after colonization suggested that immature DCs, but not B cells, are involved in Ag presentation during primary immune responses against intestinal bacteria. However, the spatial cellular relationships sequentially being established among DCs, B cells, and T cells in PPs, are most likely important for the induction of post-germinal center B cells subsequently residing within the M cell pockets.     

Patterns of genetic parameters for height in field genetic tests of Picea abies and Pinus sylvestris in Sweden

We reviewed the genetic parameter estimates carried out from 1992 to 2006 for height increment in genetic tests of Norway spruce and Scots pine, to describe patterns of genetic variation, heritability, and genetic correlations. The material included seedling and clonal tests in Sweden, aged between 5 and 20 years. Multiple regression was used to explore relationships between parameter values and test environments. Results showed moderate narrow-sense heritabilities ([^(h)]² {\hat{h}^2} : mean =0.29 in Norway spruce; mean =0.23 in Scots pine) that decreased with test site latitude for both species. In Norway spruce, [^(h)]² {\hat{h}^2} increased with better growth and decreased with tree age, while for Scots pine, [^(h)]² {\hat{h}^2} increased with tree age and southward transfer. The additive genetic coefficient of variation (; mean 15%), in Norway spruce, decreased with growth as well as site latitude. in Scots pine (mean =8.5%) increased with southward transfer and more southerly test latitude. Additive and genotypic within-site genetic age-age correlations in Norway spruce were high, with mean r _A and r _G of 0.92 and 0.85, respectively. Corresponding across-sites estimates were on average lower. Genetic parameters were better expressed on favorable sites, at younger ages in Norway spruce and at older ages in Scots pine. The results imply that gain calculations should be based on different parameters in the two species. For maximizing genetic gain in the Swedish breeding program, testing times could be shorter for Norway spruce than for Scots pine. The investigation showed a large variation in parameter estimates from different field experiments, highlighting the importance of testing over multiple sites.     

Molecular phylogeny of the Astrophorida (Porifera, Demospongiae(p)) reveals an unexpected high level of spicule homoplasy

Background

The Astrophorida (Porifera, Demospongiae ^p) is geographically and bathymetrically widely distributed. Systema Porifera currently includes five families in this order: Ancorinidae, Calthropellidae, Geodiidae, Pachastrellidae and Thrombidae. To date, molecular phylogenetic studies including Astrophorida species are scarce and offer limited sampling. Phylogenetic relationships within this order are therefore for the most part unknown and hypotheses based on morphology largely untested. Astrophorida taxa have very diverse spicule sets that make them a model of choice to investigate spicule evolution.

Methodology/Principal Findings

With a sampling of 153 specimens (9 families, 29 genera, 89 species) covering the deep- and shallow-waters worldwide, this work presents the first comprehensive molecular phylogeny of the Astrophorida, using a cytochrome c oxidase subunit I (COI) gene partial sequence and the 5′ end terminal part of the 28S rDNA gene (C1-D2 domains). The resulting tree suggested that i) the Astrophorida included some lithistid families and some Alectonidae species, ii) the sub-orders Euastrophorida and Streptosclerophorida were both polyphyletic, iii) the Geodiidae, the Ancorinidae and the Pachastrellidae were not monophyletic, iv) the Calthropellidae was part of the Geodiidae clade (Calthropella at least), and finally that v) many genera were polyphyletic (Ecionemia, Erylus, Poecillastra, Penares, Rhabdastrella, Stelletta and Vulcanella).

Conclusion

The Astrophorida is a larger order than previously considered, comprising ca. 820 species. Based on these results, we propose new classifications for the Astrophorida using both the classical rank-based nomenclature (i.e., Linnaean classification) and the phylogenetic nomenclature following the PhyloCode, independent of taxonomic rank. A key to the Astrophorida families, sub-families and genera incertae sedis is also included. Incongruences between our molecular tree and the current classification can be explained by the banality of convergent evolution and secondary loss in spicule evolution. These processes have taken place many times, in all the major clades, for megascleres and microscleres.     

Impact of concomitant DMARD therapy on adherence to treatment with etanercept and infliximab in rheumatoid arthritis. Results from a six-year observational study in southern Sweden

The objective of this work is to compare the adherence to therapy of patients receiving etanercept and infliximab during first tumour necrosis factor (TNF)-blocking treatment course in rheumatoid arthritis. Special emphasis is placed on potential predictors for treatment termination and the impact of concomitant methotrexate (MTX) or other disease-modifying antirheumatic drugs (DMARDs). Patients (n = 1,161) with active rheumatoid arthritis, not responding to at least two DMARDs including MTX starting etanercept or infliximab therapy for the first time, were included in a structured clinical follow-up protocol. Information on diagnosis, disease duration, previous and ongoing DMARDs, treatment start and termination, as well as cause of withdrawal was prospectively collected during the period of March 1999 through December 2004. Patients were divided into six groups according to TNF-blocking drugs and concomitant DMARDs. Five-year level (one-year) of adherence to therapy was 36% (69%) for patients receiving infliximab in combination with MTX compared with 65% (89%) for patients treated with etanercept and MTX (p < 0.001). Cox regression models showed that the risk for premature treatment termination of patients treated with infliximab was threefold higher than for etanercept (p < 0.001). Also, the regression analysis showed that patients receiving concomitant MTX had better treatment continuation than patients treated solely with TNF blockers (p < 0.001). Moreover, patients receiving concomitant MTX had superior drug survival than patients receiving other concomitant DMARDs (p < 0.010). The superior effect of MTX was associated primarily with fewer treatment terminations because of adverse events. In addition, the study identifies low C-reactive protein level, high age, elevated health assessment questionnaire score, and higher previous number of DMARDs as predictors of premature treatment termination. In summary, treatment with etanercept has higher adherence to therapy than treatment with infliximab. Concomitant MTX is associated with improved treatment continuation of biologics when compared with both TNF blockers as monotherapy and TNF blockers combined with other DMARDs.     

Alterations of the C-terminal end do not affect in vitro or in vivo activity of surfactant protein C analogs

The secondary structure, orientation and hydrogen/deuterium exchange of SP-C33, a surfactant protein C analog, in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/egg phosphatidylglycerol (8:2, wt./wt.) bilayers, was studied by attenuated total reflection Fourier transform infrared spectroscopy. This showed a transmembrane α-helix, in which about 55% of the amide hydrogens do not exchange for up to 20 h. Moreover, C-terminally modified SP-C33, either truncated after position 30, or having the methionine at position 31 exchanged for either lysine or isoleucine, showed the same secondary structure and orientation. The different peptides, suspended in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol 68:31 (wt./wt.), were tested for surfactant activity in vitro in a captive bubble surfactometer and in vivo in an animal model of respiratory distress syndrome using premature rabbit fetuses. All preparations showed similar surface activity in the captive bubble surfactometer. Also, in the rabbit model, all preparations performed equally well and significantly better than non-treated controls, both regarding tidal volumes and lung gas volumes. Thus, truncation or residue replacements in the C-terminal part of SP-C33 do not seem to affect membrane association or surfactant activity.     

Holocene land uplift and its influence on fire history and ecosystem development in boreal Sweden

Lake Uddjaur in northern Sweden was formed as a consequence of non‐uniform glacio‐isostatic uplift in which a forested valley was gradually flooded and high elevation areas became islands. We hypothesized that small islands in Lake Uddjaur burnt through lightning strike more frequently when they were part of a large forested area compared to when they became true islands, and that this reduction in fire impact has enhanced the domination of late successional species and humus accumulation. Fire history and vegetation dynamics were studied by analysis of macroscopic charcoal (> 0.5 mm) and pollen in humus profiles from two islands. According to a model of isostatic uplift, the islands became gradually isolated from the mainland between ca. 2000 to 1000 BP, i.e. during the same time that fire impact declined. Prior to that, both islands were part of a Pinus‐Betula forest landscape affected by fires from ca. 5800 to ca. 1500 BP. Thereafter fire influence ceased and the islands became more strongly characterized by late successional species, e.g. Picea. This change was associated with substantial humus accumulation. The decreased fire influence on these islands contrasts with the regional increase in fire influence during the last 1000 yr. Long‐term influence of wildfire is important in vegetation dynamics and humus accumulation and, thus, post‐glacial isostatic land uplift can indirectly have a substantial influence on ecosystem development. Consequently, this effect should be further considered in long‐time ecosystem studies of areas with large, non‐uniform land uplift such as those found in northern Fennoscandia and eastern Canada.