WNP: a novel algorithm for gene products annotation from weighted functional networks

Predicting the biological function of all the genes of an organism is one of the fundamental goals of computational system biology. In the last decade, high-throughput experimental methods for studying the functional interactions between gene products (GPs) have been combined with computational approaches based on Bayesian networks for data integration. The result of these computational approaches is an interaction network with weighted links representing connectivity likelihood between two functionally related GPs. The weighted network generated by these computational approaches can be used to predict annotations for functionally uncharacterized GPs. Here we introduce Weighted Network Predictor (WNP), a novel algorithm for function prediction of biologically uncharacterized GPs. Tests conducted on simulated data show that WNP outperforms other 5 state-of-the-art methods in terms of both specificity and sensitivity and that it is able to better exploit and propagate the functional and topological information of the network. We apply our method to Saccharomyces cerevisiae yeast and Arabidopsis thaliana networks and we predict Gene Ontology function for about 500 and 10000 uncharacterized GPs respectively.     

A further tessera in the two-centuries-old debate on the Hypnum cupressiforme complex (Hypnaceae, Bryopsida)

Taxonomic arrangement of Hypnum species has been controversial since the beginning of the nineteenth century. The molecular pattern and phylogenetic relationships within the Hypnum cupressiforme complex, in relation to other pleurocarps species, were investigated by study of nuclear ribosomal ITS1/ITS2 and chloroplast trnL_UAA intron sequences. Seven Hypnum species from different continents were sequenced and analysed, with a relatively large set of pleurocarpous mosses. Sequences indicate a low level of genetic differentiation within the complex. Both maximum parsimony and maximum likelihood analyses indicate that Hypnum s.l. is distributed in several clades of pleurocarps; in addition, H. cupressiforme sensu strictu, and the complex, are not monophyletic. Our results clearly circumscribe only two species, H. jutlandicum and H. imponens; phylogenetic analyses, in particular, highlight the isolation of the latter from the complex. Genetic lineages with a clear geographic structure were found in Eurasia; these probably originated during the last glaciations. The presence of H. cupressiforme in some related clades flanking the other species examined supports the occurrence of an ongoing speciation within the complex.     

Palatability, digestibility and emotional pattern in 60 healthy volunteers after ingestion of an iced dessert presented in four different flavours: a subjective evaluation

Several variables lead to changes in human and animal eating behaviour and food choices. A pivotal role is played by food palatability, represented by food, smell, taste, texture, appearance and temperature. The aim of our study is to assess the potential differences in palatability and digestibility of four different flavoured iced desserts, consumed at the end of a standardized meal, and their impact on the emotional status of 60 healthy volunteers. Sixty healthy volunteers, after ENT and psychological assessment, were asked to fill out a Psycho-Emotional Questionnaire (PEQ) to assess their basal emotional pattern before the consumption of an iced dessert at the end of a standard meal, after which they completed an Organoleptic-Sensory Questionnaire (OSQ), a Dynamic Digestibility Questionnaire (DDQ) and again the PEQ. Four different flavors (lemon, tangerine, pineapple and chocolate) were tested on 4 consecutive days on the same subjects. Most of the 60 subjects, by means of OSQ, found taste, aspect, texture and smell of the 4 flavours pleasant, lemon and tangerine were the freshest and lightest. The DDQ identified pineapple and chocolate dessert as those less digestible. By means of PEQ we recorded an improvement in joy, mood and activation, associated with good data of digestibility and palatability after the consumption of all flavors. Our data showed that all flavors improve joy, mood and activation, after their consumption, without statistically significant differences. However, among the tested flavours, lemon and tangerine appear to be the most pleasant and those which facilitate the digestive process.     

In vitro exposure of human osteoarthritic chondrocytes to ELF fields and new therapeutic application of musically modulated electromagnetic fields: biological evidence

Osteoarthritis (OA) is the most frequently occurring rheumatic disease, caused by metabolic changes in chondrocytes, the cells that maintain cartilage. Treatment with electromagnetic fields (MF) produces benefits in patients affected by this pathology. Isolated human osteoarthritic (OA) chondrocytes were cultured in vitro under standard conditions or stimulated with IL-1beta or IGF-1, to mimic the imbalance between chondroformation and chondroresorption processes observed in OA cartilage in vivo. The cells were exposed for a specific time to extremely low frequency (ELF; 100-Hz) electromagnetic fields and to the Therapeutic Application of Musically Modulated Electromagnetic Fields (TAMMEF), which are characterized by variable frequencies, intensities, and waveforms. Using flow cytometry, we tested the effects of the different types of exposure on chondrocyte metabolism. The exposure of the cells to both systems enhances cell proliferation, does not generate reactive oxygen species, does not cause glutathione depletion or changes in mitochondrial transmembrane potential and does not induce apoptosis. This study presents scientific support to the fact that MF could influence OA chondrocytes from different points of view (viability, ROS production and apoptosis). We can conclude that both ELF and TAMMEF systems could be recommended for OA therapy and represent a valid non-pharmacological approach to the treatment of this pathology.     

Maternal gametic transmission of translocations or inversions of human chromosome 11p15.5 results in regional DNA hypermethylation and downregulation of CDKN1C expression

Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome associated with genetic or epigenetic alterations in one of two imprinted domains on chromosome 11p15.5. Rarely, chromosomal translocations or inversions of chromosome 11p15.5 are associated with BWS but the molecular pathophysiology in such cases is not understood. In our series of 3 translocation and 2 inversion patients with BWS, the chromosome 11p15.5 breakpoints map within the centromeric imprinted domain, 2. We hypothesized that either microdeletions/microduplications adjacent to the breakpoints could disrupt genomic sequences important for imprinted gene regulation. An alternate hypothesis was that epigenetic alterations of as yet unknown regulatory DNA sequences, result in the BWS phenotype. A high resolution Nimblegen custom microarray was designed representing all non-repetitive sequences in the telomeric 33 Mb of the short arm of human chromosome 11. For the BWS-associated chromosome 11p15.5 translocations and inversions, we found no evidence of microdeletions/microduplications. DNA methylation was also tested on this microarray using the HpaII tiny fragment enrichment by ligation-mediated PCR (HELP) assay. This high-resolution DNA methylation microarray analysis revealed a gain of DNA methylation in the translocation/inversion patients affecting the p-ter segment of chromosome 11p15, including both imprinted domains. BWS patients that inherited a maternal translocation or inversion also demonstrated reduced expression of the growth suppressing imprinted gene, CDKN1C in Domain 2. In summary, our data demonstrate that translocations and inversions involving imprinted domain 2 on chromosome 11p15.5, alter regional DNA methylation patterns and imprinted gene expression in cis, suggesting that these epigenetic alterations are generated by an alteration in "chromatin context".     

An original clinical methodology for non-invasive assessment of pivot-shift test

Even if pivot-shift (PS) test has been clinically used to specifically detect anterior cruciate ligament (ACL) injury, the main problem in using this combined test has been yet associated with the difficulty of clearly quantifying its outcome. The goal of this study was to describe an original non-invasive methodology used to quantify PS test, highlighting its possible clinical reliability. The method was validated on 66 consecutive unilateral ACL-injured patients. A commercial triaxial accelerometer was non-invasively mounted on patient's tibia, the corresponding 3D acceleration was acquired during PS test execution and a set of specific parameters were automatically identified on the signal to quantify the test. PS test was repeated three times on both injured and controlateral limbs. Reliability of the method was found to be good (mean intra-rater intraclass correlation coefficient was 0.79); moreover, we found that ACL-deficient knees presented statistically higher values for the identified parameters - than the controlateral healthy limbs, averagely reporting also large effect size.     

Identification of a new susceptibility variant for multiple sclerosis in OAS1 by population genetics analysis

Contrasting results have been reported concerning the association of a splice-site polymorphism (rs10774671) in OAS1 with multiple sclerosis (MS). We analysed two OAS1 regions encompassing alternatively spliced exons. While the region carrying the splice-site variant is neutrally evolving, a signature of long-standing balancing selection was observed across an alternative exon 7. Analysis of variants in this exon identified an insertion/deletion polymorphism (rs11352835, A/?) that originates predicted products with distinct C termini. This variant is located along the major branch of the haplotype genealogy, suggesting that it may represent the selection target. A case/control study for MS indicated that rs11352835 is associated with disease susceptibility (for an allelic model with the deleted allele predisposing to MS, OR 1.27, 95% CI 1.072?C1.513, p?=?0.010). No association was found between rs10774671 and MS. As the two SNPs are in linkage disequilibrium in Europeans, the previously reported association between rs10774671 and MS susceptibility might be driven by rs11352835, possibly explaining the contrasting results previously observed for the splice-site polymorphism. Thus, we describe a novel susceptibility variant for MS in OAS1 and show that population genetic analyses can be instrumental to the identification of selection targets and, consequently, of functional polymorphisms with an effect on phenotypic traits.