Evaluating facilitators' challenges administering a program building on existing strengths in families facing difficulties.

The primary objective of this study was to understand the challenges faced by 12 facilitators (9 women and 3 men) of the Strengthening Families Program (SFP) implemented in the Adélard-Dugré and Jean-Nicolet neighbourhoods of Trois-Rivières, Quebec. This objective was operationalized as the following question: How did facilitators manage to buy in to, and align themselves with, program principles while avoiding an expert stance and remaining focused on participating families' strengths? This question has not been investigated before in connection with the SFP program. This study was conducted between 2011 and 2014, and relied on semi-annual group interviews. The results indicate that facilitators' first step was to acknowledge their expectations. Once they had accomplished this, they were able to let go and distance themselves from an expert stance. This allowed them to recognize the benefits flowing from application of the program's principles, and understand how they could repurpose their expertise for intervention with program participants. Facilitators also came to realize that they had developed strong relationships with the families and better understood the latter's realities. Finally, this article explores the implications of the results, both for practice (in terms of program compliance) and research (in terms of program evaluation).

Computational identification of RNA functional determinants by three-dimensional quantitative structure-activity relationships.

Anti-infection drugs target vital functions of infectious agents, including their ribosome and other essential non-coding RNAs. One of the reasons infectious agents become resistant to drugs is due to mutations that eliminate drug-binding affinity while maintaining vital elements. Identifying these elements is based on the determination of viable and lethal mutants and associated structures. However, determining the structure of enough mutants at high resolution is not always possible. Here, we introduce a new computational method, MC-3DQSAR, to determine the vital elements of target RNA structure from mutagenesis and available high-resolution data. We applied the method to further characterize the structural determinants of the bacterial 23S ribosomal RNA sarcin-ricin loop (SRL), as well as those of the lead-activated and hammerhead ribozymes. The method was accurate in confirming experimentally determined essential structural elements and predicting the viability of new SRL variants, which were either observed in bacteria or validated in bacterial growth assays. Our results indicate that MC-3DQSAR could be used systematically to evaluate the drug-target potentials of any RNA sites using current high-resolution structural data.

An efficient method for exploring the space of gene tree/species tree reconciliations in a probabilistic framework.

BACKGROUND: Inferring an evolutionary scenario for a gene family is a fundamental problem with applications both in functional and evolutionary genomics. The gene tree/species tree reconciliation approach has been widely used to address this problem, but mostly in a discrete parsimony framework that aims at minimizing the number of gene duplications and/or gene losses. Recently, a probabilistic approach has been developed, based on the classical birth-and-death process, including efficient algorithms for computing posterior probabilities of reconciliations and orthology prediction. RESULTS: In previous work, we described an algorithm for exploring the whole space of gene tree/species tree reconciliations, that we adapt here to compute efficiently the posterior probability of such reconciliations. These posterior probabilities can be either computed exactly or approximated, depending on the reconciliation space size. We use this algorithm to analyze the probabilistic landscape of the space of reconciliations for a real data set of fungal gene families and several data sets of synthetic gene trees. CONCLUSION: The results of our simulations suggest that, with exact gene trees obtained by a simple birth-and-death process and realistic gene duplication/loss rates, a very small subset of all reconciliations needs to be explored in order to approximate very closely the posterior probability of the most likely reconciliations. For cases where the posterior probability mass is more evenly dispersed, our method allows to explore efficiently the required subspace of reconciliations.

Space of gene/species trees reconciliations and parsimonious models.

We describe algorithms to study the space of all possible reconciliations between a gene tree and a species tree, that is counting the size of this space, uniformly generate a random reconciliation, and exploring this space in optimal time using combinatorial operators. We also extend these algorithms for optimal and sub-optimal reconciliations according to the three usual combinatorial costs (duplication, loss, and mutation). Applying these algorithms to simulated and real gene family evolutionary scenarios, we observe that the LCA (Last Common Ancestor) based reconciliation is almost always identical to the real one.

Modeling RNA tertiary structure motifs by graph-grammars.

A new approach, graph-grammars, to encode RNA tertiary structure patterns is introduced and exemplified with the classical sarcin-ricin motif. The sarcin-ricin motif is found in the stem of the crucial ribosomal loop E (also referred to as the sarcin-ricin loop), which is sensitive to the alpha-sarcin and ricin toxins. Here, we generate a graph-grammar for the sarcin-ricin motif and apply it to derive putative sequences that would fold in this motif. The biological relevance of the derived sequences is confirmed by a comparison with those found in known sarcin-ricin sites in an alignment of over 800 bacterial 23S ribosomal RNAs. The comparison raised alternative alignments in few sarcin-ricin sites, which were assessed using tertiary structure predictions and 3D modeling. The sarcin-ricin motif graph-grammar was built with indivisible nucleotide interaction cycles that were recently observed in structured RNAs. A comparison of the sequences and 3D structures of each cycle that constitute the sarcin-ricin motif gave us additional insights about RNA sequence-structure relationships. In particular, this analysis revealed the sequence space of an RNA motif depends on a structural context that goes beyond the single base pairing and base-stacking interactions.