Endoscopic management of duodenal perforations caused by migrated biliary plastic stents.

 Duodenal perforation by migration of plastic stents placed to treat biliary lesions is rare but can be life-threatening. Surgical management is preferred, but it may increase risks of mortality and morbidity, especially in patients with underlying comorbidities and those of advanced age. We describe five cases of duodenal perforation that were successfully managed endoscopically.

Leveraging prior information to detect causal variants via multi-variant regression.

Although many methods are available to test sequence variants for association with complex diseases and traits, methods that specifically seek to identify causal variants are less developed. Here we develop and evaluate a Bayesian hierarchical regression method that incorporates prior information on the likelihood of variant causality through weighting of variant effects. By simulation studies using both simulated and real sequence variants, we compared a standard single variant test for analyzing variant-disease association with the proposed method using different weighting schemes.

Widespread recruitment of ancient domain structures in modern enzymes during metabolic evolution.

Protein domains sometime combine to form multidomain proteins and are acquired or lost in lineages of organisms. These processes are ubiquitous in modern metabolism. To sort out evolutionary patterns of domain recruitment, we developed an algorithm that derives the most plausible ancestry of an enzyme from structural and evolutionary annotations in the MANET database.

Genomic and proteomic studies on the effects of the insect growth regulator diflubenzuron in the model beetle species Tribolium castaneum.

Several benzoylphenyl urea-derived insecticides such as diflubenzuron (DFB, Dimilin) are in wide use to control various insect pests. Although this class of compounds is known to disrupt molting and to affect chitin content, their precise mode of action is still not understood. To gain a broader insight into the mechanism underlying the insecticidal effects of benzoylphenyl urea compounds, we conducted a comprehensive study with the model beetle species and stored product pest Tribolium castaneum (red flour beetle) utilizing genomic and proteomic approaches.

BeetleBase in 2010: revisions to provide comprehensive genomic information for Tribolium castaneum.

BeetleBase (http://www.beetlebase.org) has been updated to provide more comprehensive genomic information for the red flour beetle Tribolium castaneum.

The origin and evolution of modern metabolism.

One fundamental goal of current research is to understand how complex biomolecular networks took the form that we observe today. Cellular metabolism is probably one of the most ancient biological networks and constitutes a good model system for the study of network evolution. While many evolutionary models have been proposed, a substantial body of work suggests metabolic pathways evolve fundamentally by recruitment, in which enzymes are drawn from close or distant regions of the network to perform novel chemistries or use different substrates.

Origins and evolution of modern biochemistry: insights from genomes and molecular structure.

The survey of components in living systems at different levels of organization enables an evolutionary exploration of patterns and processes in macromolecules, networks, and genomic repertoires. Here we discuss how phylogenetic strategies that generate intrinsically rooted phylogenies impact the evolutionary study of RNA and protein components of the macromolecular machinery that is responsible for biological function. We used these methods to generate timelines of discovery of components in systems, such as substructures in RNA molecules, architectures in proteomes, domains in multi-domain proteins, enzymes in metabolic networks, and protein architectures in proteomes.

The origin of modern metabolic networks inferred from phylogenomic analysis of protein architecture.

Metabolism represents a complex collection of enzymatic reactions and transport processes that convert metabolites into molecules capable of supporting cellular life. Here we explore the origins and evolution of modern metabolism. Using phylogenomic information linked to the structure of metabolic enzymes, we sort out recruitment processes and discover that most enzymatic activities were associated with the nine most ancient and widely distributed protein fold architectures.

MANET: tracing evolution of protein architecture in metabolic networks.

Background: Cellular metabolism can be characterized by networks of enzymatic reactions and transport processes capable of supporting cellular life. Our aim is to find evolutionary patterns and processes embedded in the architecture and function of modern metabolism, using information derived from structural genomics.

Description: The Molecular Ancestry Network (MANET) project traces evolution of protein architecture in biomolecular networks.