Molecular dynamics simulations of bio-active phosphate-based glass surfaces

Classical molecular dynamics (MD) simulations were used to study the structural changes in the surfaces of biocompatible phosphate glasses with compositions (P2O5)0.45(CaO)x(Na2O)0.55 − x (x = 30, 35, 40) to evaluate their effect on the solubility of the material. Direct comparison of the data for the three compositions highlighted the critical role that an enhancement in Na+ concentration plays in the hydrolysis of the material, which is responsible for the release of network components into solution. The calculations also confirm that the most soluble material is (P2O5)0.45(CaO)0.30(Na2O)0.25, has the lowest calcium coordination number, thereby causing fewer cross links to phosphate chains

Comprehensive epigenetic landscape of rheumatoid arthritis fibroblast-like synoviocytes.

Epigenetics contributes to the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first comprehensive epigenomic characterization of RA fibroblast-like synoviocytes (FLS), including histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3), open chromatin, RNA expression and whole-genome DNA methylation. To address complex multidimensional relationship and reveal epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles. Epigenomically similar regions exist in RA cells and are associated with active enhancers and promoters and specific transcription factor binding motifs. Differentially marked genes are enriched for immunological and unexpected pathways, with "Huntington's Disease Signaling" identified as particularly prominent. We validate the relevance of this pathway to RA by showing that Huntingtin-interacting protein-1 regulates FLS invasion into matrix. This work establishes a high-resolution epigenomic landscape of RA and demonstrates the potential for integrative analyses to identify unanticipated therapeutic targets

Structures and properties of phosphate-based bioactive glasses from computer simulation: a review

Phosphate-based bioactive glasses (PBGs) dissolve harmlessly in the body with a dissolution rate which depends sensitively on composition. This makes them proposed vectors for e.g. drug delivery, or other applications where an active component needs to be delivered at a therapeutically appropriate rate. Molecular dynamics (MD) simulations provide atomic-level structural information about PBG compositions. We review recent work to show that MD is an excellent tool to unravel the connections between the PBG glass composition, its atomic structure, and its dissolution rate, which can help to optimise PBGs for specific medical applications

A methodology for the capture and analysis of hybrid data: a case study of program debugging

No description supplie

Systems-biology analysis of rheumatoid arthritis fibroblast-like synoviocytes implicates cell line-specific transcription factor function

Rheumatoid arthritis (RA) is an immune-mediated disease affecting diarthrodial joints that remains an unmet medical need despite improved therapy. This limitation likely reflects the diversity of pathogenic pathways in RA, with individual patients demonstrating variable responses to targeted therapies. Better understanding of RA pathogenesis would be aided by a more complete characterization of the disease. To tackle this challenge, we develop and apply a systems biology approach to identify important transcription factors (TFs) in individual RA fibroblast-like synoviocyte (FLS) cell lines by integrating transcriptomic and epigenomic information. Based on the relative importance of the identified TFs, we stratify the RA FLS cell lines into two subtypes with distinct phenotypes and predicted active pathways. We biologically validate these predictions for the top subtype-specific TF RARα and demonstrate differential regulation of TGFβ signaling in the two subtypes. This study characterizes clusters of RA cell lines with distinctive TF biology by integrating transcriptomic and epigenomic data, which could pave the way towards a greater understanding of disease heterogeneity

A sex-chromosome mutation in Silene latifolia

Silene latifolia is dioecious, yet rare hermaphrodites have been found, and such natural mutants can provide valuable insight into genetic mechanisms. Here, we describe a hermaphrodite-inducing mutation that is almost certainly localized to the gynoecium-suppression region of the Y chromosome in S. latifolia. The mutant Y chromosome was passed through the megaspore, and the presence of two X chromosomes was not necessary for seed development in the parent. This result supports a lack of degeneration of the Y chromosome in S. latifolia, consistent with the relatively recent formation of the sex chromosomes in this species. When crossed to wild-type plants, hermaphrodites performed poorly as females, producing low seed numbers. When hermaphrodites were pollen donors, the sex ratio of offspring they produced through crosses was biased towards females. This suggests that hermaphroditic S. latifolia would fail to thrive and potentially explains the rarity of hermaphrodites in natural populations of S. latifolia. These results indicate that the Y chromosome in Silene latifolia remains very similar to the X, perhaps mostly differing in the primary sex determination regions

Caspase‐8 variant G regulates rheumatoid arthritis fibroblast‐like synoviocyte aggressive behavior

Objective: Fibroblast-like synoviocytes (FLS) play a pivotal role in rheumatoid arthritis (RA) by contributing to synovial inflammation and progressive joint damage. An imprinted epigenetic state is associated with the FLS aggressive phenotype. We identified CASP8 (encoding for caspase-8) as a differentially marked gene and evaluated its pathogenic role in RA FLSs. Methods: RA FLS lines were obtained from synovial tissues at arthroplasty and used at passage 5-8. Caspase-8 was silenced using small interfering RNA, and its effect was determined in cell adhesion, migration and invasion assays. Quantitative reverse transcription PCR and western blot were used to assess gene and protein expression, respectively. A caspase-8 selective inhibitor was used determine the role of enzymatic activity on FLS migration and invasion. Caspase-8 isoform transcripts and epigenetic marks in FLSs were analyzed in FLS public databases. Crystal structures of caspase-8B and G were determined. Results: Caspase-8 deficiency in RA FLSs reduced cell adhesion, migration, and invasion independent of its catalytic activity. Epigenetic and transcriptomic analyses of RA FLSs revealed that a specific caspase-8 isoform, variant G, is the dominant isoform expressed (~80% of total caspase-8) and induced by PDGF. The crystal structures of caspase-8 variant G and B were identical except for a unique unstructured 59 amino acid N-terminal domain in variant G. Selective knockdown of caspase-8G was solely responsible for the effects of caspase-8 on calpain activity and cell invasion in FLS. Conclusion: Blocking caspase-8 variant G could decrease cell invasion in diseases like RA without the potential deleterious effects of nonspecific caspase-8 inhibition

Natural parenting : back to basics in infant care

Peer reviewe

Neonatal Handling Affects Durably Bonding and Social Development

The neonatal period in humans and in most mammals is characterized by intense mother-young interactions favoring pair bonding and the adaptation of neonates to their new environment. However, in many post-delivery procedures, human babies commonly experience combined maternal separation and intense handling for about one hour post-birth. Currently, the effects of such disturbances on later attachment and on the development of newborns are still debated: clearly, further investigations are required. As animals present good models for controlled experimentation, we chose domestic horses to investigate this issue. Horses, like humans, are characterized by single births, long lactating periods and selective mother-infant bonds. Routine postnatal procedures for foals, as for human babies, also involve intense handling and maternal separation. In the present study, we monitored the behavior of foals from early stages of development to “adolescence”, in a normal ecological context (social groups with adults and peers). Experimental foals, separated from their mothers and handled for only 1 hour post-birth, were compared to control foals, left undisturbed after birth. Our results revealed short- and long-term effects of this unique neonatal experience on attachment and subsequent social competences. Thus, experimental foals presented patterns of insecure attachment to their mothers (strong dependence on their mothers, little play) and impaired social competences (social withdrawal, aggressiveness) at all ages. We discuss these results in terms of mother-young interactions, timing of interactions and relationships between bonding and subsequent social competences. Our results indicate that this ungulate species could become an interesting animal model. To our knowledge, this is the first clear demonstration that intervention just after birth affects bonding and subsequent social competences (at least until “adolescence”). It opens new research directions for studies on both humans and other animals