Hip joint replacement surgery for idiopathic osteoarthritis aggregates in families

In order to determine whether there is a genetic component to hip or knee joint failure due to idiopathic osteoarthritis (OA), we invited patients (probands) undergoing hip or knee arthroplasty for management of idiopathic OA to provide detailed family histories regarding the prevalence of idiopathic OA requiring joint replacement in their siblings. We also invited their spouses to provide detailed family histories about their siblings to serve as a control group. In the probands, we confirmed the diagnosis of idiopathic OA using American College of Rheumatology criteria. The cohorts included the siblings of 635 probands undergoing total hip replacement, the siblings of 486 probands undergoing total knee replacement, and the siblings of 787 spouses. We compared the prevalence of arthroplasty for idiopathic OA among the siblings of the probands with that among the siblings of the spouses, and we used logistic regression to identify independent risk factors for hip and knee arthroplasty in the siblings. Familial aggregation for hip arthroplasty, but not for knee arthroplasty, was observed after controlling for age and sex, suggesting a genetic contribution to end-stage hip OA but not to end-stage knee OA. We conclude that attempts to identify genes that predispose to idiopathic OA resulting in joint failure are more likely to be successful in patients with hip OA than in those with knee OA.     

Protein folding: looping from hydrophobic nuclei.

Protein structure can be viewed as a compact linear array of nearly standard size closed loops of 25-30 amino acid residues (Berezovsky et al., FEBS Letters 2000; 466: 283-286) irrespective of details of secondary structure. The end-to-end contacts in the loops are likely to be hydrophobic, which is a testable hypothesis. This notion could be verified by direct comparison of the loop maps with Kyte and Doolittle hydropathicity plots. This analysis reveals that most of the ends of the loops are hydrophobic, indeed. The same conclusion is reached on the basis of positional autocorrelation analysis of protein sequences of 23 fully sequenced bacterial genomes. Hydrophobic residues valine, alanine, glycine, leucine, and isoleucine appear preferentially at the 25-30 residues distance one from another. These observations open a new perspective in the understanding of protein structure and folding: a consecutive looping of the polypeptide chain with the loops ending primarily at hydrophobic nuclei.     

In silico single strand melting curve: a new approach to identify nucleic acid polymorphisms in Totiviridae

Background

The PCR technique and its variations have been increasingly used in the clinical laboratory and recent advances in this field generated new higher resolution techniques based on nucleic acid denaturation dynamics. The principle of these new molecular tools is based on the comparison of melting profiles, after denaturation of a DNA double strand. Until now, the secondary structure of single-stranded nucleic acids has not been exploited to develop identification systems based on PCR. To test the potential of single-strand RNA denaturation as a new alternative to detect specific nucleic acid variations, sequences from viruses of the Totiviridae family were compared using a new in silico melting curve approach. This family comprises double-stranded RNA virus, with a genome constituted by two ORFs, ORF1 and ORF2, which encodes the capsid/RNA binding proteins and an RNA-dependent RNA polymerase (RdRp), respectively.

Results

A phylogenetic tree based on RdRp amino acid sequences was constructed, and eight monophyletic groups were defined. Alignments of RdRp RNA sequences from each group were screened to identify RNA regions with conserved secondary structure. One region in the second half of ORF2 was identified and individually modeled using the RNAfold tool. Afterwards, each DNA or RNA sequence was denatured in silico using the softwares MELTSIM and RNAheat that generate melting curves considering the denaturation of a double stranded DNA and single stranded RNA, respectively. The same groups identified in the RdRp phylogenetic tree were retrieved by a clustering analysis of the melting curves data obtained from RNAheat. Moreover, the same approach was used to successfully discriminate different variants of Trichomonas vaginalis virus, which was not possible by the visual comparison of the double stranded melting curves generated by MELTSIM.

Conclusion

In silico analysis indicate that ssRNA melting curves are more informative than dsDNA melting curves. Furthermore, conserved RNA structures may be determined from analysis of individuals that are phylogenetically related, and these regions may be used to support the reconstitution of their phylogenetic groups. These findings are a robust basis for the development of in vitro systems to ssRNA melting curves detection.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2105-15-243) contains supplementary material, which is available to authorized users.     

Coevolution of DNA-interacting proteins and genome "dialect"

Several species-specific characteristics of genome organization that are superimposed on its coding aspects were proposed earlier, including genome signature (GS), genome accent, and compositional spectrum (CS). These notions could be considered as representatives of genome dialect (GD). We measured within the Proteobacteria some GD representatives, the relative abundance of dinucleotides or GS, the profiles of occurrence of 10 nucleotide words (CS), and the profiles of occurrence of 20 nucleotide words, using a degenerate two-letter alphabet (purine-pyrimidine compositional spectra [PPCS]). Here, we show that the evolutionary distances between DNA repair and recombination orthologous enzymes (especially those of the nucleotide excision repair system) are highly correlated with PPCS and GS distances. Orthologous proteins involved in structural or metabolic processes (control group) have significantly lower correlations of their evolutionary distances with the PPCS and GS distances. We hypothesize that the high correlation of the evolutionary distances of the DNA repair orthologous enzymes with their GD is a result of the coevolution of the DNA repair enzymes' structures and GDs. Species GDs could be substantially influenced by the function of DNA polymerase I (the bacterial major DNA repair polymerase). This might cause the correlation of species GDs differentiation with evolutionary changes of species DNA polymerase I. Simultaneously, the structures of DNA repair-recombination enzymes might be evolutionarily sensitive and responsive to changes in the structure of their substrate-the DNA (including those that are represented by GD differentiation). We further discuss the rationale and mechanisms of the hypothesized coevolution. We suggest that stress might be an important cause of changes in the repair-recombination genes and the GD and the trigger of the aforementioned coevolution process. Other triggers might be massive horizontal gene transfer and ecological selection.     

Human Wharton’s Jelly Mesenchymal Stem Cells Plasticity Augments Scar-Free Skin Wound Healing with Hair Growth

Human mesenchymal stem cells (MSCs) are a promising candidate for cell-based transplantation and regenerative medicine therapies. Thus in the present study Wharton’s Jelly Mesenchymal Stem Cells (WJ-MSCs) have been derived from extra embryonic umbilical cord matrix following removal of both arteries and vein. Also, to overcome the clinical limitations posed by fetal bovine serum (FBS) supplementation because of xenogeneic origin of FBS, usual FBS cell culture supplement has been replaced with human platelet lysate (HPL). Apart from general characteristic features of bone marrow-derived MSCs, wharton jelly-derived MSCs have the ability to maintain phenotypic attributes, cell growth kinetics, cell cycle pattern, in vitro multilineage differentiation plasticity, apoptotic pattern, normal karyotype-like intrinsic mesenchymal stem cell properties in long-term in vitro cultures. Moreover, the WJ-MSCs exhibited the in vitro multilineage differentiation capacity by giving rise to differentiated cells of not only mesodermal lineage but also to the cells of ectodermal and endodermal lineage. Also, WJ-MSC did not present any aberrant cell state upon in vivo transplantation in SCID mice and in vitro soft agar assays. The immunomodulatory potential assessed by gene expression levels of immunomodulatory factors upon exposure to inflammatory cytokines in the fetal WJ-MSCs was relatively higher compared to adult bone marrow-derived MSCs. WJ-MSCs seeded on decellularized amniotic membrane scaffold transplantation on the skin injury of SCID mice model demonstrates that combination of WJ-MSCs and decellularized amniotic membrane scaffold exhibited significantly better wound-healing capabilities, having reduced scar formation with hair growth and improved biomechanical properties of regenerated skin compared to WJ-MSCs alone. Further, our experimental data indicate that indocyanin green (ICG) at optimal concentration can be resourcefully used for labeling of stem cells and in vivo tracking by near infrared fluorescence non-invasive live cell imaging of labelled transplanted cells, thus proving its utility for therapeutic applications.     

Heritability of cortisol response to confinement stress in European sea bass dicentrarchus labrax

Background

In fish, the most studied production traits in terms of heritability are body weight or growth, stress or disease resistance, while heritability of cortisol levels, widely used as a measure of response to stress, is less studied. In this study, we have estimated heritabilities of two growth traits (body weight and length) and of cortisol response to confinement stress in the European sea bass.

Findings

The F1 progeny analysed (n = 922) belonged to a small effective breeding population with contributions from an unbalanced family structure of just 10 males and 2 females. Heritability values ranged from 0.54 (±0.21) for body weight to 0.65 (±0.22) for standard body length and were low for cortisol response i.e. 0.08 (±0.06). Genetic correlations were positive (0.94) between standard body length and body weight and negative between cortisol and body weight and between cortisol and standard body length (−0.60 and −0.55, respectively).

Conclusion

This study confirms that in European sea bass, heritability of growth-related traits is high and that selection on such traits has potential. However, heritability of cortisol response to stress is low in European sea bass and since it is known to vary greatly among species, further studies are necessary to understand the reasons for these differences.     

A large-scale comparison of genomic sequences: one promising approach

We introduce a novel, linguistic-like method of genome analysis. We propose a natural approach to characterizing genomic sequences based on occurrences of fixed length words from a predefined, sufficiently large set of words (strings over the alphabet {A, C, G, T} ). A measure based on this approach is called compositional spectrum and is actually a histogram of imperfect word occurrences. Our results assert that the compositional spectrum is an overall characteristic of a long sequence i.e., a complete genome or an uninterrupted part of a chromosome. This attribute is manifested in the similarity of spectra obtained on different stretches of the same genome, and simultaneously in a broad range of dissimilarities between spectral representations of different genomes. High flexibility characterizes this approach due to imperfect matching and as a result sets of relatively long words can be considered. The proposed approach may have various applications in intra- and intergenomic sequence comparisons.     

Protein sequences yield a proteomic code

Analysis of crystallized protein structures suggests that globular proteins are organized as consecutively connected units of 25-35 residues. These units are closed loops, that is returns of the polypeptide chain trajectory to a close contact with itself. This universal feature of apparently polymer-statistical nature is a basis for a principally novel view on the globular proteins as loop fold structures. The same unit size has been detected in protein sequences translated from complete prokaryotic genomes by positional autocorrelation analysis, which strongly indicates the evolutionary connection of the units. The units are further characterized by prototype sequences matching to their numerous derivatives in the translated genomes. The matches to five strongest prokaryotic prototypes and three prototypes of C. elegans are identified in the sequences of crystallized proteins, and their structures analyzed. Corresponding segments of the polypeptide chains in majority of cases form closed loops, though evolutionary fate of every prototype element is shown to be rather diverse. Then loop ends can be separated by a sequence-wise distant segments and stabilized by the spatial interactions in the context of the overall globular structure. The units belong to a presumably limited spectrum of the sequence prototypes, full repertoire of which would constitute a proteomic code.     

Different Clustering of Genomes Across Life Using the A-T-C-G and Degenerate R-Y Alphabets: Early and Late Signaling on Genome Evolution?

In this study, we have calculated distances between genomes based on our previously developed compositional spectra (CS) analysis. The study was conducted using genomes of 39 species of Eukarya, Eubacteria, and Archaea. Based on CS distances, we produced two different consensus dendrograms for four- and two-letter (purine-pyrimidine) alphabets. A comparison of the obtained structure using purine-pyrimidine alphabet with the standard three-kingdom (3K) scheme reveals substantial similarity. Surprisingly, this is not the case when the same procedure is based on the four-letter alphabet. In this situation, we also found three main clusters-but different from those in the 3K scheme. In particular, one of the clusters includes Eukarya and thermophilic bacteria and a part of the considered Archaea species. We speculate that the key factor in the last classification (based on the A-T-G-C alphabet) is related to ecology: two ecological parameters, temperature and oxygen, distinctly explain the clustering revealed by compositional spectra in the four-letter alphabet. Therefore, we assume that this result reflects two interdependent processes: evolutionary divergence and superimposed ecological convergence of the genomes, albeit another process, horizontal transfer, cannot be excluded as an important contributing factor.