Phenomic, convergent functional genomic, and biomarker studies in a stress-reactive genetic animal model of bipolar disorder and co-morbid alcoholism.

We had previously identified the clock gene D-box binding protein (Dbp) as a potential candidate gene for bipolar disorder and for alcoholism, using a Convergent Functional Genomics (CFG) approach. Here we report that mice with a homozygous deletion of DBP have lower locomotor activity, blunted responses to stimulants, and gain less weight over time. In response to a chronic stress paradigm, these mice exhibit a diametric switch in these phenotypes. DBP knockout mice are also activated by sleep deprivation, similar to bipolar patients, and that activation is prevented by treatment with the mood stabilizer drug valproate. Moreover, these mice show increased alcohol intake following exposure to stress. Microarray studies of brain and blood reveal a pattern of gene expression changes that may explain the observed phenotypes. CFG analysis of the gene expression changes identified a series of novel candidate genes and blood biomarkers for bipolar disorder, alcoholism, and stress reactivity.

Convergent Functional Genomics of bipolar disorder: from animal model pharmacogenomics to human genetics and biomarkers.

Progress in understanding the genetic and neurobiological basis of bipolar disorder(s) has come from both human studies and animal model studies. Until recently, the lack of concerted integration between the two approaches has been hindering the pace of discovery, or more exactly, constituted a missed opportunity to accelerate our understanding of this complex and heterogeneous group of disorders. Our group has helped overcome this "lost in translation" barrier by developing an approach called convergent functional genomics (CFG). The approach integrates animal model gene expression data with human genetic linkage/association data, as well as human tissue (postmortem brain, blood) data. This Bayesian strategy for cross-validating findings extracts meaning from large datasets, and prioritizes candidate genes, pathways and mechanisms for subsequent targeted, hypothesis-driven research. The CFG approach may also be particularly useful for identification of blood biomarkers of the illness.

Comparison of growth and performance in upland and lowland switchgrass types to water and nitrogen stress.

The objective of the study was to examine lowland (Alamo and Kanlow) and upland (Blackwell and Caddo) cultivars of switchgrass (Panicum virgatum L.) for differences in response to water deficit and nitrogen fertilizer. Cultivars were grown in pots with fritted clay at two water levels: well watered and deficit conditions (-0.1 and -1.0 MPa) and two nitrogen levels (10 and 100 kg ha(-1)). Nitrogen determined growth potential of the cultivars more than water availability. The lowland cultivars produced greater biomass yields than upland cultivars. However, upland cultivars showed a smaller response to drought stress. Under water stress conditions all cultivars exhibited a higher leaf percentage of total dry matter (DM), with the upland cultivars having the highest leaf percentage of total DM. Nitrogen proved to have more of an effect on single-leaf photosynthesis rates than water. Alamo demonstrated the greatest biomass production among all cultivars. The differences found between the two lowland cultivars suggest that Alamo would be better suited for forage and biomass production in central Texas, being a higher producer under drought and non-drought conditions than Kanlow as well as upland cultivars.

Nutrient movement and removal in a switchgrass biomass-filter strip system treated with dairy manure.

Manure use on cropland has raised concern about nutrient contamination of surface and ground waters. Warm-season perennial grasses may be useful in filter strips to trap manure nutrients and as biomass feedstock for nutrient removal. We explored the use of 'Alamo' switchgrass (Panicum virgatum L.) in a biomass production-filter strip system treated with dairy manure. We measured changes in extractable P in the soil, NO3 -N in soil water, and changes in total reactive P and chemical oxygen demand (COD) of runoff water before and after a switchgrass filter strip. Five rates of dairy manure (target rates of 0, 50, 100, 150, and 200 kg N ha(-1) from solid manure in 1995; 0, 75, 150, 300, and 600 kg N ha(-1) from lagoon effluent in 1996 and 1997) were surface-applied to field plots of switchgrass (5.2 by 16.4 m) with a 5.2- by 16.4-m switchgrass filter strip below the manured area. Yield of switchgrass from the manured area increased linearly with increasing manure rate in each year. Soil water samples collected at 46 or 91 cm below the soil surface on 30 dates indicated < 3 mg L(-1) of NO3-N in all plots. Concentrations of total reactive P in surface runoff water were reduced an average of 47% for the 150 kg N rate and 76% for the 600 kg N rate in 1996 and 1997 after passing through the strip. Manure could effectively substitute for inorganic fertilizer in switchgrass biomass production with dual use of the switchgrass as a vegetative filter strip.