The ABC transporter gene family of Caenorhabditis elegans has implications for the evolutionary dynamics of multidrug resistance in eukaryotes

BACKGROUND: Many drugs of natural origin are hydrophobic and can pass through cell membranes. Hydrophobic molecules must be susceptible to active efflux systems if they are to be maintained at lower concentrations in cells than in their environment. Multi-drug resistance (MDR), often mediated by intrinsic membrane proteins that couple energy to drug efflux, provides this function. All eukaryotic genomes encode several gene families capable of encoding MDR functions, among which the ABC transporters are the largest. The number of candidate MDR genes means that study of the drug-resistance properties of an organism cannot be effectively carried out without taking a genomic perspective. RESULTS: We have annotated sequences for all 60 ABC transporters from the Caenorhabditis elegans genome, and performed a phylogenetic analysis of these along with the 49 human, 30 yeast, and 57 fly ABC transporters currently available in GenBank. Classification according to a unified nomenclature is presented. Comparison between genomes reveals much gene duplication and loss, and surprisingly little orthology among analogous genes. Proteins capable of conferring MDR are found in several distinct subfamilies and are likely to have arisen independently multiple times. CONCLUSIONS: ABC transporter evolution fits a pattern expected from a process termed 'dynamic-coherence'. This is an unusual result for such a highly conserved gene family as this one, present in all domains of cellular life. Mechanistically, this may result from the broad substrate specificity of some ABC proteins, which both reduces selection against gene loss, and leads to the facile sorting of functions among paralogs following gene duplication

Phylogenetic relationships of Indian caecilians (Amphibia: Gymnophiona) inferred from mitochondrial rRNA gene sequences

India has a diverse caecilian fauna, including representatives of three of the six currently recognized families, the Caeciliidae, Ichthyophiidae, the endemic Uraeotyphlidae, but previous molecular phylogenetic studies of caecilians have not included sequences for any Indian caecilians. Partial 12S and 16S mitochondrial gene sequences were obtained for a single representative of each of the caecilian families found in India and aligned against previously reported sequences for 13 caecilian species. The resulting alignment (16 taxa, 1200 sites, of which 288 cannot be aligned unambiguously) was analyzed using parsimony, maximum-likelihood, and distance methods. As judged by bootstrap proportions, decay indices, and leaf stabilities, well-supported relationships of the Indian caecilians are recovered from the alignment. The data (1) corroborate the hypothesis, based on morphology, that the Uraeotyphlidae and Ichthyophiidae are sister taxa, (2) recover a monophyletic Ichthyophiidae, including Indian and South East Asian representatives, and (3) place the Indian caeciliid Gegeneophis ramaswamii as the sister group of the caeciliid caecilians of the Seychelles. Rough estimates of divergence times suggest an origin of the Uraeotyphlidae and Ichthyophiidae while India was isolated from Laurasia and Africa and are most consistent with an Indian origin of these families and subsequent dispersal of ichthyophiids into South East Asia

Centralized, Stepped, Patient Preference–Based Treatment for Patients With Post–Acute Coronary Syndrome Depression

IMPORTANCE: Controversy remains about whether depression can be successfully managed after acute coronary syndrome (ACS) and the costs and benefits of doing so. OBJECTIVE: To determine the effects of providing post-ACS depression care on depressive symptoms and health care costs. DESIGN: Multicenter randomized controlled trial. SETTING: Patients were recruited from 2 private and 5 academic ambulatory centers across the United States. PARTICIPANTS: A total of 150 patients with elevated depressive symptoms (Beck Depression Inventory [BDI] score ≥10) 2 to 6 months after an ACS, recruited between March 18, 2010, and January 9, 2012. INTERVENTIONS: Patients were randomized to 6 months of centralized depression care (patient preference for problem-solving treatment given via telephone or the Internet, pharmacotherapy, both, or neither), stepped every 6 to 8 weeks (active treatment group; n = 73), or to locally determined depression care after physician notification about the patient's depressive symptoms (usual care group; n = 77). MAIN OUTCOME MEASURES: Change in depressive symptoms during 6 months and total health care costs. RESULTS: Depressive symptoms decreased significantly more in the active treatment group than in the usual care group (differential change between groups, -3.5 BDI points; 95% CI, -6.1 to -0.7; P = .01). Although mental health care estimated costs were higher for active treatment than for usual care, overall health care estimated costs were not significantly different (difference adjusting for confounding, -$325; 95$2639 to $1989; P = .78). CONCLUSIONS: For patients with post-ACS depression, active treatment had a substantial beneficial effect on depressive symptoms. This kind of depression care is feasible, effective, and may be cost-neutral within 6 months; therefore, it should be tested in a large phase 3 pragmatic trial. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01032018

Proceedings of the fourth Resilience Engineering Symposium

These proceedings document the various presentations at the Fourth Resilience Engineering Symposium held on June 8-10, 2011, in Sophia-Antipolis, France. The Symposium gathered participants from five continents and provided them with a forum to exchange experiences and problems, and to learn about Resilience Engineering from the latest scientific achievements to recent practical applications. The First Resilience Engineering Symposium was held in Söderköping, Sweden, on October 25-29 2004. The Second Resilience Engineering Symposium was held in Juan-les-Pins, France, on November 8-10 2006, The Third Resilience Engineering Symposium was held in Juan-les-Pins, France, on October 28-30 2008. Since the first Symposium, resilience engineering has fast become recognised as a valuable complement to the established approaches to safety. Both industry and academia have recognised that resilience engineering offers valuable conceptual and practical basis that can be used to attack the problems of interconnectedness and intractability of complex socio-technical systems. The concepts and principles of resilience engineering have been tested and refined by applications in such fields as air traffic management, offshore production, patient safety, and commercial fishing. Continued work has also made it clear that resilience is neither limited to handling threats and disturbances, nor confined to situations where something can go wrong. Today, resilience is understood as the intrinsic ability of a system to adjust its functioning prior to, during, or following changes and disturbances, so that it can sustain required operations under both expected and unexpected conditions. This definition emphasizes the ability to continue functioning, rather than simply to react and recover from disturbances and the ability to deal with diverse conditions of functioning, expected as well as unexpected. For anyone who is interested in learning more about Resilience Engineering, the books published in the Ashgate Studies in Resilience Engineering provide an excellent starting point. Another sign that Resilience Engineering is coming of age is the establishment of the Resilience Engineering Association. The goal of this association is to provide a forum for coordination and exchange of experiences, by bringing together researchers and professionals working in the Resilience Engineering domain and organisations applying or willing to apply Resilience Engineering principles in their operations. The Resilience Engineering Association held its first General Assembly during the Fourth Symposium, and will in the future play an active role in the organisation of symposia and other activities related to Resilience Engineering