Computational identification of gene over-expression targets for metabolic engineering of taxadiene production.

Taxadiene is the first dedicated intermediate in the biosynthetic pathway of the anticancer compound Taxol. Recent studies have taken advantage of heterologous hosts to produce taxadiene and other isoprenoid compounds, and such ventures now offer research opportunities that take advantage of the engineering tools associated with the surrogate host. In this study, metabolic engineering was applied in the context of over-expression targets predicted to improve taxadiene production. Identified targets included genes both within and outside of the isoprenoid precursor pathway. These targets were then tested for experimental over-expression in a heterologous Escherichia coli host designed to support isoprenoid biosynthesis. Results confirmed the computationally predicted improvements and indicated a synergy between targets within the expected isoprenoid precursor pathway and those outside this pathway. The presented algorithm is broadly applicable to other host systems and/or product choices.

Methods and options for the heterologous production of complex natural products.

This review will detail the motivations, experimental approaches, and growing list of successful cases associated with the heterologous production of complex natural products.

Oppositional defiant disorder.

Oppositional defiant disorder is defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., as a recurrent pattern of developmentally inappropriate, negativistic, defiant, and disobedient behavior toward authority figures. This behavior often appears in the preschool years, but initially it can be difficult to distinguish from developmentally appropriate, albeit troublesome, behavior. Children who develop a stable pattern of oppositional behavior during their preschool years are likely to go on to have oppositional defiant disorder during their elementary school years. Children with oppositional defiant disorder have substantially strained relationships with their parents, teachers, and peers, and have high rates of coexisting conditions such as attention-deficit/hyperactivity disorder and mood disorders. Children with oppositional defiant disorder are at greater risk of developing conduct disorder and antisocial personality disorder during adulthood. Psychological intervention with both parents and child can substantially improve short- and long-term outcomes. Research supports the effectiveness of parent training and collaborative problem solving. Collaborative problem solving is a psychological intervention that aims to develop a child's skills in tolerating frustration, being flexible, and avoiding emotional overreaction. When oppositional defiant disorder coexists with attention-deficit/hyperactivity disorder, stimulant therapy can reduce the symptoms of both disorders.

Opiate dependence treatment with buprenorphine: one year's experience in a family practice residency setting.

Buprenorphine became available for office-based treatment of opiate dependence in January 2003, at which time the Underwood-Memorial Hospital Family Practice Residency Program began offering buprenorphine treatment at its family practice center. This article describes the patient selection process, outcomes, and obstacles to treatment. Patients who had a pharmaceutical benefit were much more likely to remain in treatment than those who had to pay for the medication. The authors are not aware of other residency programs currently providing buprenorphine training, and postulate reasons why family physicians in the United States have not readily adopted the office-based opiate treatment model.