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A nonimmune library of 10 9 human antibody scFv fragments has been cloned and expressed on the surface of yeast, and nanomolar-affinity scFvs routinely obtained by magnetic bead screening and flow-cytometric sorting. The yeast library can be amplified 10 10 -fold without measurable loss of clonal diversity, allowing its effectively indefinite expansion. The expression, stability, and antigen-binding properties of >50 isolated scFv clones were assessed directly on the yeast cell surface by immunofluorescent labeling and flow cytometry, obviating separate subcloning, expression, and purification steps and thereby expediting the isolation of novel affinity reagents. The ability to use multiplex library screening demonstrates the usefulness of this approach for high-throughput antibody isolation for proteomics applications.

The genome of the japonica subspecies of rice, an important cereal and model monocot, was sequenced and assembled by whole-genome shotgun sequencing. The assembled sequence covers 93% of the 420-megabase genome. Gene predictions on the assembled sequence suggest that the genome contains 32,000 to 50,000 genes. Homologs of 98% of the known maize, wheat, and barley proteins are found in rice. Synteny and gene homology between rice and the other cereal genomes are extensive, whereas synteny with Arabidopsis is limited. Assignment of candidate rice orthologs to Arabidopsis genes is possible in many cases. The rice genome sequence provides a foundation for the improvement of cereals, our most important crops.

A putative tumor suppressor locus on the short arm of human chromosome 9 has been localized to a region of less than 40 kilobases by means of homozygous deletions in melanoma cell lines. This region contained a gene, Multiple Tumor Suppressor 1 (MTS1), that encodes a previously identified inhibitor (p16) of cyclin-dependent kinase 4. MTS1 was homozygously deleted at high frequency in cell lines derived from tumors of lung, breast, brain, bone, skin, bladder, kidney, ovary, and lymphocyte. Melanoma cell lines that carried at least one copy of MTS1 frequently carried nonsense, missense, or frameshift mutations in the gene. These findings suggest that MTS1 mutations are involved in tumor formation in a wide range of tissues.

The p21 region of human chromosome 9 is thought to contain a gene (MLM) involved in genetic susceptibility to melanoma and a gene or genes that influence progression of certain other tumors. Genomic clones that span a large region in 9p21 surrounding the presumptive tumor suppressor gene(s) have been isolated. A set of sequence-tagged sites in this region has been developed. By using these markers and others previously reported, the 9p21 region has been studied by physical mapping in 84 melanoma cell lines. A putative tumor suppressor gene, perhaps MLM itself, has been localized to a region of less than 40 kb that lies proximal (centromeric) to the α-interferon gene cluster.

Loss of heterozygosity data from familial tumors suggest that BRCA1, a gene that confers susceptibility to ovarian and early-onset breast cancer, encodes a tumor suppressor. The BRCA1 region is also subject to allelic loss in sporadic breast and ovarian cancers, an indication that BRCA1 mutations may occur somatically in these tumors. The BRCA1 coding region was examined for mutations in primary breast and ovarian tumors that show allele loss at the BRCA1 locus. Mutations were detected in 3 of 32 breast and 1 of 12 ovarian carcinomas; all four mutations were germline alterations and occurred in early-onset cancers. These results suggest that mutation of BRCA1 may not be critical in the development of the majority of breast and ovarian cancers that arise in the absence of a mutant germline allele.

In aquatic ecosystems, sediments serve as a reservoir for neutral organic chemicals such as PCB-52 which partition primarily to the lipids of the biota and the organic carbon of the sediment. The bioaccumulation potential predicts adverse chronic effects which result from the uptake and retention of a persistant chemical by the aquatic biota. The biota-sediment accumulation factor (BSAF) is a measure of bioaccumulation potential used in hazard assessment. Mathematically, the BSAF is the ratio of an organism's concentration of a particular chemical to the sediment concentration of the same chemical, normalized to biota lipid and sediment organic carbon. If an aquatic ecosystem is considered as a series of compartments reversibly connected with each other, then chemicals can move dynamically in and out of these compartments at different rates. Toxicokinetic modeling using the intercompartmental transfer rate constants of closed compartmental models can be used to express this movement. In this study, two- and three-compartment closed models were developed to describe the phase distribution of PCB-52 among fish, sediment, and water. Integration of the simultaneous differential rate equations of each model provided a set of predictive time-course equations. Fish and suspended sediment were simultaneously and separately exposed to an aqueous solution of PCB-52. Intercompartmental transfer rate constants were generated by fitting differential equations to the experimental data. Coefficients and hybrid rate constants of the integrated equations were obtained indirectly from the transfer rate constants and directly from fitting the experimental data to the integrated equations. Uptake of PCB-52 by fish (Compartment 3), adsorption of PCB-52 by sediment (Compartment 2), and decline of PCB-52 in water (compartment 1) were rapid. For simultaneous exposures, an initial rapid adsorption of PCB-52 by sediment was followed by a gradual desorption which was reflected in a gradual uptake by fish. Intercompartmental transfer rate constants ranged from 0.0023 h$\\sp{-1}$ (Japanese medakas to water) to 0.5381 h$\\sp{-1}$ (water to Barataria Bay sediment). Generally, for all exposure systems, k$\\sb{12} \\ge$ k$\\sb{21} >$ k$\\sb{13} \\gg$ k$\\sb{31}$. No significant difference (p $>$ 0.05) was found between indirectly and directly generated coefficients and hybrid rate constants. BSAFs calculated from the intercompartmental transfer rate constants of the separate and simultaneous exposures ranged from 1.03 to 4.35 and were within the reported range of literature values for PCB-52. Analysis of variance of BSAF values obtained from simultaneous exposures indicated that no significant difference existed between BSAFs according to sediment type. Differences in TOC of the sediments appeared to account for differential adsorption and desorption of PCB-52 by the sediments. A significant difference (p $<$ 0.05) which appeared to correlate with differences in ventilation volume, was found between the BSAFs of the fish species. Differences in lipid content of the fish species did not completely explain differences in uptake and elimination of PCB-52 by fish. Short-term kinetic studies offer a simple, more accurate, and more economical means of predicting BSAFs than long-term equilibrium partitioning studies. The three-compartment closed model developed in this project was able to successfully predict reliable BSAFs. These novel methods of predicting the bioaccumulation potential provide a new tool for use in the hazard assessment of polluted sediments.