RNA and protein 3D structure modeling: similarities and differences

In analogy to proteins, the function of RNA depends on its structure and dynamics, which are encoded in the linear sequence. While there are numerous methods for computational prediction of protein 3D structure from sequence, there have been very few such methods for RNA. This review discusses template-based and template-free approaches for macromolecular structure prediction, with special emphasis on comparison between the already tried-and-tested methods for protein structure modeling and the very recently developed “protein-like” modeling methods for RNA. We highlight analogies between many successful methods for modeling of these two types of biological macromolecules and argue that RNA 3D structure can be modeled using “protein-like” methodology. We also highlight the areas where the differences between RNA and proteins require the development of RNA-specific solutions.     

Comprehensive characterisation of pulmonary and serum surfactant protein D in COPD

Background

Pulmonary surfactant protein D (SP-D) is considered as a candidate biomarker for the functional integrity of the lung and for disease progression, which can be detected in serum. The origin of SP-D in serum and how serum concentrations are related to pulmonary concentrations under inflammatory conditions is still unclear.

Methods

In a cross-sectional study comprising non-smokers (n = 10), young - (n = 10), elderly smokers (n = 20), and smokers with COPD (n = 20) we simultaneously analysed pulmonary and serum SP-D levels with regard to pulmonary function, exercise, repeatability and its quaternary structure by native gel electrophoresis. Statistical comparisons were conducted by ANOVA and post-hoc testing for multiple comparisons; repeatability was assessed by Bland-Altman analysis.

Results

In COPD, median (IQR) pulmonary SP-D levels were lower (129(68) ng/ml) compared to smokers (young: 299(190), elderly: 296(158) ng/ml; p < 0.01) and non-smokers (967(708) ng/ml; p < 0.001). The opposite was observed in serum, with higher concentrations in COPD (140(89) ng/ml) as compared to non-smokers (76(47) ng/ml; p < 0.01). SP-D levels were reproducible and correlated with the degree of airway obstruction in all smokers. In addition, smoking lead to disruption of the quaternary structure.

Conclusions

Pulmonary and serum SP-D levels are stable markers influenced by smoking and related to airflow obstruction and disease state. Smaller subunits of pulmonary SP-D and the rapid increase of serum SP-D levels in COPD due to exercise support the translocation hypothesis and its use as a COPD biomarker.

Trial registration

no interventional trial     

Tet Proteins Connect the O-Linked N-acetylglucosamine Transferase Ogt to Chromatin in Embryonic Stem Cells

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Highlights? Ogt forms a complex with Tet1 and Tet2 in the nucleus of embryonic stem cells ? Ogt preferentially associates with promoter regions in proximity of TSS ? Ogt shows >90% of colocalization with Tet1 at methylation-free CpG-rich elements ? Tet1 is required for global Ogt chromatin recruitment regulating its activity     

Hepatic CYP1A induction in rainbow trout (Oncorhynchus mykiss) after exposure to benzo[a]pyrene in water

Juvenile rainbow trout were exposed to unlabelled benzo[a]pyrene BaP and ³H benzo a pyrene (³H BaP), in a static exposure system for 2 days. The initial concentration was 30 μg l^-1 and 0.625 μCi l^-1, corresponding to 6 mg kg^-1 body weight and 125 μCi kg^-1 body weight. Hepatic 7-ethoxyresorufin-O-deethylase (EROD) activity was measured during the exposure and depuration periods, elucidating the time course pattern of CYP1A induction. Maximum induction (11-fold) of EROD activity was observed on day 2 after addition of BaP to the water. Tissue distribution of ³H-BaP was studied by liquid scintillation counting and whole body autoradiography. The concentration of ³H-BaP-derived radioactivity was highest in the bile at all sampling times. High levels of radiolabelled compound were also present in the gills, liver and the olfactory organ. There was an overall decrease in all tissues during the depuration period. The elimination of ³H-BaP-derived radioactivity from the gills, however, was slow compared with liver and blood (6.2 days vs 2.7 and 2.9 days, respectively).     

Graphemic alternations in English as a reflex of morphological structure

Graphemic alternations such as <y>-replacement (e.g. <lady–ladies>) are obligatory in inflectional processes, but they do not occur in compounding (cf. <ladybug, *ladibug>). In derivational processes, the obligatoriness varies depending on the suffix (cf. <happiness, puppydom>). This variation in graphemic alternations is used to determine the juncture strength of derivational products. On the basis of the 450 million word Corpus of Contemporary American English (CoCA), 46 suffixes are investigated. The resulting scale is found to correlate closely with the type parsing ratio from Hay and Baayen (in Yearbook of Morphology 2001, pp. 203–235, 2002), a purely morphological measure. As the graphemic alternations investigated are not mirrored in phonology, the results are taken to be an argument for a partly autonomous writing system that can in turn be used to argue for or against morphological structure, quite like phonological sandhi or liaison phenomena.     

Joint Loads in Marsupial Ankles Reflect Habitual Bipedalism versus Quadrupedalism

Joint surfaces of limb bones are loaded in compression by reaction forces generated from body weight and musculotendon complexes bridging them. In general, joints of eutherian mammals have regions of high radiodensity subchondral bone that are better at resisting compressive forces than low radiodensity subchondral bone. Identifying similar form-function relationships between subchondral radiodensity distribution and joint load distribution within the marsupial postcranium, in addition to providing a richer understanding of marsupial functional morphology, can serve as a phylogenetic control in evaluating analogous relationships within eutherian mammals. Where commonalities are established across phylogenetic borders, unifying principles in mammalian physiology, morphology, and behavior can be identified. Here, we assess subchondral radiodensity patterns in distal tibiae of several marsupial taxa characterized by different habitual activities (e.g., locomotion). Computed tomography scanning, maximum intensity projection maps, and pixel counting were used to quantify radiodensity in 41 distal tibiae of bipedal (5 species), arboreal quadrupedal (4 species), and terrestrial quadrupedal (5 species) marsupials. Bipeds (Macropus and Wallabia) exhibit more expansive areas of high radiodensity in the distal tibia than arboreal (Dendrolagus, Phascolarctos, and Trichosurus) or terrestrial quadrupeds (Sarcophilus, Thylacinus, Lasiorhinus, and Vombatus), which may reflect the former carrying body weight only through the hind limbs. Arboreal quadrupeds exhibit smallest areas of high radiodensity, though they differ non-significantly from terrestrial quadrupeds. This could indicate slightly more compliant gaits by arboreal quadrupeds compared to terrestrial quadrupeds. The observed radiodensity patterns in marsupial tibiae, though their statistical differences disappear when controlling for phylogeny, corroborate previously documented patterns in primates and xenarthrans, potentially reflecting inferred limb use during habitual activities such as locomotion. Despite the complex nature of factors contributing to joint loads, broad observance of these patterns across joints and across a variety of taxa suggests that subchondral radiodensity can be used as a unifying form-function principle within Mammalia.     

Strong Impact of Temporal Resolution on the Structure of an Ecological Network

Most ecological networks are analysed as static structures, where all observed species and links are present simultaneously. However, this is over-simplified, because networks are temporally dynamical. We resolved an arctic, entire-season plant-flower visitor network into a temporal series of 1-day networks and compared the properties with its static equivalent based on data pooled over the entire season. Several properties differed. The nested link pattern in the static network was blurred in the dynamical version, because the characteristic long nestedness tail of flower–visitor specialists got stunted in the dynamical networks. This tail comprised a small food web of pollinators, parasitoids and hyper-parasitoids. The dynamical network had strong time delays in the transmission of direct and indirect effects among species. Twenty percent of all indirect links were impossible in the dynamical network. Consequently, properties and thus also robustness of ecological networks cannot be deduced from the static topology alone.     

CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients

Introduction

Single-nucleotide polymorphisms (SNPs) in the CRP gene are implicated in the regulation of the constitutional C-reactive protein (CRP) expression and its response to proinflammatory stimuli. Previous reports suggest that these effects may have an impact on clinical decision-making tools based on CRP, such as the Disease Activity Score in 28 joints (DAS28). We aimed to investigate the possible association between seven CRP SNPs, their haplotypes and the serum levels of CRP, as well as DAS28 scores, in two cohorts of untreated active early rheumatoid arthritis (RA) patients followed during their initial treatment.

Methods

Overall, 315 patients with RA from two randomized controlled trials (the CIMESTRA and OPERA trials) who were naïve to disease-modifying antirheumatic drugs and steroids with disease durations less than 6 months were included. Seven CRP SNPs were investigated: rs11265257, rs1130864, rs1205, rs1800947, rs2808632, rs3093077 and rs876538. The genotype and haplotype associations with CRP and DAS28 levels were evaluated using linear regression analysis adjusted for age, sex and treatment.

Results

The minor allele of rs1205 C > T was associated with decreased CRP levels at baseline (P = 0.03), with the TT genotype having a 50% reduction in CRP from 16.7 to 8.4 mg/L (P = 0.005) compared to homozygosity of the major allele, but no association was observed at year 1 (P = 0.38). The common H2 haplotype, characterized by the T allele of rs1205, was associated with a 26% reduction in CRP at baseline (P = 0.043), although no effect was observed at year 1 (P = 0.466). No other SNP or haplotype was associated with CRP at baseline or at year 1 (P ≥0.09). We observed no associations between SNPs or haplotypes and DAS28 scores at baseline or at year 1 (P ≥0.10).

Conclusion

CRP genotype and haplotype were only marginally associated with serum CRP levels and had no association with the DAS28 score. This study shows that DAS28, the core parameter for inflammatory activity in RA, can be used for clinical decision-making without adjustment for CRP gene variants.

Trial registration

The OPERA study is registered at Clinicaltrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT00660647","term_id":"NCT00660647"}}NCT00660647). The CIMESTRA study is not listed in a clinical trials registry, because patients were included between October 1999 and October 2002.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-014-0475-3) contains supplementary material, which is available to authorized users.