The TT Genotype of the STAT4 rs7574865 Polymorphism Is Associated with High Disease Activity and Disability in Patients with Early Arthritis

Background

The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis.

Methodology and Results

We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5′ allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01–0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = −0.27 [−0.56– −0.01], p = 0.042; TT genotype = −0.68 [−1.64– −0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype.

Conclusions

Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.     

A phylogenetic approach to total evaporative water loss in mammals

Abstract Maintaining appropriate water balance is a constant challenge for terrestrial mammals, and this problem can be exacerbated in desiccating environments. It has been proposed that natural selection has provided desert-dwelling mammals physiological mechanisms to reduce rates of total evaporative water loss. In this study, we evaluated the relationship between total evaporative water loss and body mass in mammals by using a recent phylogenetic hypothesis. We compared total evaporative water loss in 80 species of arid-zone mammals to that in 56 species that inhabit mesic regions, ranging in size from 4 g to 3,500 kg, to test the hypothesis that mammals from arid environments have lower rates of total evaporative water loss than mammals from mesic environments once phylogeny is taken into account. We found that arid species had lower rates of total evaporative water loss than mesic species when using a dichotomous variable to describe habitat (arid or mesic). We also found that total evaporative water loss was negatively correlated with the average maximum and minimum environmental temperature as well as the maximum vapor pressure deficit of the environment. Annual precipitation and the variable Q (a measure of habitat aridity) were positively correlated with total evaporative water loss. These results support the hypothesis that desert-dwelling mammals have lower rates of total evaporative water loss than mesic species after controlling for body mass and evolutionary relatedness regardless of whether categorical or continuous variables are used to describe habitat.     

Teruelia diezii gen. et sp. nov.: an early polysporangiophyte from the Lower Devonian of the Iberian Peninsula

A new basal land plant, Teruelia diezii gen. et sp. nov., is described from the shallow‐water marine deposits of the Lower Devonian (Lochkovian–Pragian) Nogueras Formation of the Iberian Peninsula (north Gondwana palaeocontinent). Teruelia is preserved as a compression fossil and consists of isotomously branched, robust stems terminated in large, fusiform, twisted sporangia. This morphology suggests that Teruelia is very probably equivalent to Aglaophyton, a permineralized early polysporangiophyte known up to now only from the Lower Devonian (early Pragian to ?earliest Emsian) Rhynie Chert in Scotland (Laurussia palaeocontinent), which represents an early terrestrial hot‐spring ecosystem. Accepted phylogenies identify Aglaophyton as sister to vascular plants. Our phylogeny‐based results identify the Aglaophyton/Teruelia biological entity (i.e. Aglaophyton anatomical characters plus Teruelia external morphology) as the most direct vascular plant precursor. It shows that at least one Rhynie Chert type plant had a much wider distribution than previously known and suggests that Aglaophyton was not restricted to hydrothermal environments, unlike other Rhynie Chert plants.     

Stress-induced effects on feeding behavior and growth performance of the sea bass (<Emphasis Type="Italic">Dicentrarchus labrax</Emphasis>): a self-feeding approach

Repetitive aquaculture-related protocols may act as cyclic stressors that induce chronic stress in cultured fish. The sea bass is particularly sensitive to stressful conditions and the mere presence of humans will disturb feeding behavior. In this paper, we study whether chronic stress induced by repetition of acute stress protocols affects long-term feeding behavior and growth performance in sea bass and whether exogenous cortisol may induce stress-like changes in these parameters. We demonstrate that both chronic stress and dietary cortisol decrease food intake and have a negative effect on feed conversion efficiency, severely impairing sea bass performance. Both experimental approaches induced changes in the daily feeding activity by lengthening the active feeding periods. Fish subjected to a cyclic stressor modify their daily feeding pattern in an attempt to avoid interference with the time of the stressor. The delay in feeding when fish are acutely and repeatedly stressed could be of substantial adaptive importance.     

Characterization of a bacteriocin-producing strain of Enterococcus faecalis from cow’s milk used in the production of Moroccan traditional dairy foods

A bacteriocin-producing lactic acid bacterium (strain 2.5) isolated from cow’s milk used in cheese production from Northern Morocco was selected for its strong anti-listerial activity. The producer strain was identified as Enterococcus faecalis by molecular methods. Strain 2.5 carried the genetic determinants for the two-peptide enterococcal bacteriocin enterocin 1071, and the active bacteriocin was purified to homogeneity by reversed-phase chromatography from culture broths of the producer strain. Strain 2.5 carried two plasmids (of ∼7 and 40 kb). Characterization of strain 2.5 at biosafety level indicated that this strain is non-haemolytic, and lacks the genetic determinants for most of the virulence factors described in enterococci (cylB, cylM, gelE, ace and agg) although it carried the genetic determinants cylA, efaAfs as well as determinants for the sex pheromone peptides cpd, cob, and ccf. Strain 2.5 was resistant to tetracycline, rifampicin, and ciprofloxacin, but it was sensitive to penicillin, ampicillin, vancomycin, and teicoplanin. Results from the present study support the potential role of strain 2.5 as an anti-listerial agent to be tested in traditional fermented foods.     

Hybrid larch heterosis: for which traits and under which genetic control?

RCD1 is a member of the plant-specific SRO protein family. Several SRO genes have been functionally identified in the regulation of abiotic stresses in Arabidopsis and other plant species. However, the function of SROs is largely unknown in apple (Malus×domestica). In this study, six MdSRO-encoding genes were isolated, categorized into two types and mapped to six chromosomes. The phylogenetic analysis demonstrated that the sequences of the AtSRO and MdSRO proteins are highly conserved. Subsequently, expression analysis showed that MdSRO genes had different expression profiles in different tissues and in response to various stresses. Finally, MdRCD1 was isolated for functional identification. The results showed that resistance to oxidation stress in apple calli was enhanced by MdRCD1 overexpression and weakened by MdRCD1 suppression. MdRCD1 also played a crucial role in the regulation of ROS homeostasis in transgenic apple calli and Arabidopsis. Ectopic expression of MdRCD1 significantly enhanced resistance to salt and oxidative stresses in transgenic lines. In addition, MdRCD1 also enhanced drought tolerance due to its influence on stomatal opening. Based on these results, we conclude that MdRCD1 is an important regulator in abiotic stress response.

     

Characterization of juvenile maritime pine (Pinus pinaster Ait.) ectomycorrhizal fungal community using morphotyping, direct sequencing and fruitbodies sampling

Using ectomycorrhizal root tip morphotyping (anatomical and morphological identification), molecular analysis (internal transcribed spacer region amplification and sequencing), and fruitbody sampling, we assessed diversity and composition of the ectomycorrhizal fungal community colonizing juvenile Pinus pinaster Ait. under natural conditions in NW Spain. Overall, we found 15 Basidiomycetes and two Ascomycetes. Members of the family Thelephoraceae represented up to 59.4% of the samples. The most frequent species was Tomentella sublilacina followed by Thelephora terrestris, Russula drimeia, Suillus bovinus, and Paxillus involutus, while the less frequent were Pseudotomentella tristis, Lactarius subdulcis, Russula ochroleuca, and Entoloma conferendum. From October 2007 to June 2008, we sampled 208 sporocarps belonging to seven genera and nine species: Thelephora terrestris, Paxillus involutus, Suillus bovinus, Xerocomus badius, Scleroderma verrucosum, Amanita gemmata, A. rubescens, Amanita sp., and Russula sp. The species belonging to the genus Amanita, X. badius and S. verrucosum were not found on root samples. By comparing our results with a bibliographic review of papers published from 1922 to 2006, we found five genera and six species which have not been previously reported in symbiosis with P. pinaster. This is the first time that the diversity of the ectomycorrhizal fungal community associated with P. pinaster was investigated using molecular techniques. Considering that only 38% of the genera found by sequencing were found as fruitbodies, we conclude that integrating morphotyping and sporocarps surveys with molecular analysis of ectomycorrhizas is important to documenting the ectomycorrhizal fungus community. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Systematics and evolution of Carex sects. Spirostachyae and Elatae (Cyperaceae)

Carex sect. Spirostachyae comprises 25 species displaying the centre of diversity in Eurasia, while sect. Elatae comprises 22 species displaying the centre of diversity in tropical African mountainous regions. Phylogenetic analysis of the 136 ITS and 108 5′trnK intron sequences of 23 species of sect. Spirostachyae and 20 species of sect. Elatae revealed that neither section is monophyletic. With the exclusion of C. montis-eeka (sect. Spirostachyae) and C. insularis, C. iynx and C. longibrachiata (sect. Elatae), the sects. Spirostachyae and Elatae constitute a monophyletic group of 38 species, 22 of which were previously included in sect. Spirostachyae and 16 of which were in sect. Elatae (considering C. thomasii as C. mannii ssp. thomasii). Two main groups with different edaphic preferences were identified in the core Spirostachyae, in congruence with some morphological features. One group comprises primarily acidophilus species including 11 species of sect. Spirostachyae and 16 species of sect. Elatae. The other group includes 11 basophilic species of sect. Spirostachyae. Incongruence between nuclear and plastid genomes was detected, suggesting hybridization or lineage sorting processes in the evolution of the core Spirostachyae.     

Tuning of the FMN binding and oxido-reduction properties by neighboring side chains in Anabaena flavodoxin

Contribution of three regions (phosphate-binding, 50’s and 90’s loops) of Anabaena apoflavodoxin to FMN binding and reduction potential was studied. Thr12 and Glu16 did not influence FMN redox properties, but Thr12 played a role in FMN binding. Replacement of Trp57 with Glu, Lys or Arg moderately shifted E_ox/sq and E_sq/hq and altered the energetic of the FMN redox states binding profile. Our data indicate that the side chain of position 57 does not modulate E_ox/sq by aromatic stacking or solvent exclusion, but rather by influencing the relative strength of the H-bond between the N(5) of the flavin and the Asn58-Ile59 bond. A correlation was observed between the isoalloxazine increase in solvent accessibility and less negative E_sq/hq. Moreover, E_sq/hq became less negative as positively charged residues were added near to the isoalloxazine. Ile59 and Ile92 were simultaneously mutated to Ala or Glu. These mutations impaired FMN binding, while shifting E_sq/hq to less negative values and E_ox/sq to more negative. These effects are discussed on the bases of the X-ray structures of some of the Fld mutants, suggesting that in Anabaena Fld the structural control of both electron transfer steps is much more subtle than in other Flds.