Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana.

The genome of the flowering plant Arabidopsis thaliana has five chromosomes. Here we report the sequence of the largest, chromosome 1, in two contigs of around 14.2 and 14.6 megabases. The contigs extend from the telomeres to the centromeric borders, regions rich in transposons, retrotransposons and repetitive elements such as the 180-base-pair repeat. The chromosome represents 25% of the genome and contains about 6,850 open reading frames, 236 transfer RNAs (tRNAs) and 12 small nuclear RNAs. There are two clusters of tRNA genes at different places on the chromosome. One consists of 27 tRNA(Pro) genes and the other contains 27 tandem repeats of tRNA(Tyr)-tRNA(Tyr)-tRNA(Ser) genes. Chromosome 1 contains about 300 gene families with clustered duplications. There are also many repeat elements, representing 8% of the sequence.

Dimer preparation that mimics the transition state for the adsorption of H2 on the Si(100)-2 x 1 surface.

A chemically induced dimer configuration was prepared on the silicon (Si) (100) surface and was characterized by scanning tunneling microscopy (STM) and spectroscopy (STS). These prepared dimers, which are essentially untilted and differ both electronically and structurally from the dynamically tilting dimers normally found on this surface, are more reactive than normal dimers. For molecular hydrogen (H2) adsorption, the enhancement is about 10(9) at room temperature. There is no appreciable barrier for the H2 reaction at prepared sites, indicating the prepared configuration closely approximates the actual dimer structure in the transition state. This previously unknown ability to prepare specific surface configurations has important implications for understanding and controlling reaction dynamics on semiconductor surfaces.

DNA sequence chromatogram browsing using JAVA and CORBA.

DNA sequence chromatograms (traces) are the primary data source for all large-scale genomic and expressed sequence tags (ESTs) sequencing projects. Access to the sequencing trace assists many later analyses, for example contig assembly and polymorphism detection, but obtaining and using traces is problematic. Traces are not collected and published centrally, they are much larger than the base calls derived from them, and viewing them requires the interactivity of a local graphical client with local data. To provide efficient global access to DNA traces, we developed a client/server system based on flexible Java components integrated into other applications including an applet for use in a WWW browser and a stand-alone trace viewer. Client/server interaction is facilitated by CORBA middleware which provides a well-defined interface, a naming service, and location independence. [The software is packaged as a Jar file available from the following URL: http://www.ebi.ac.uk/jparsons. Links to working examples of the trace viewers can be found at http://corba.ebi.ac.uk/EST. All the Washington University mouse EST traces are available for browsing at the same URL.]

Nonspecific hypersensitivity: false-positive responses with the use of Freund's complete adjuvant.

While conducting a guinea pig sensitization protocol, using the maximization test, it was discovered, at challenge, that the test animals were more responsive to the vehicle (acetone) than they were to the proprietary test material. During rechallenge, conducted to clarify the specific immune status of the test animals, it was determined that they were also hyperreactive to an alternate vehicle (diethyl phthalate), to which they were naïve. This bizarre set of data is presented and it is suggested that this type of response is the prototype for the presence of false-positive responses experienced by toxicologists using this test. The test conditions imposed on the immune system by the maximization test that could result in these anomalous results are discussed. These data suggest that investigators need cautiously to interpret data that are produced by the injection of Freund's complete adjuvant (FCA).

Occlusive patch method for skin sensitization in guinea pigs: the Buehler method.

Currently, the European Community is in the process of discussing the details of how to conduct various protocols for safety assessment. Additionally, there is a desire that these protocols be harmonized internationally. This presentation attempts to describe the critical and non-critical parameters of the protocol for detecting potential contact allergens in the guinea pig and also discusses some controversial issues. It is also emphasized that the identification of a test material as a potential sensitizer is only the first step in the risk-assessment exercise.

Possible genes for left heart formation on 11q23.3.

A case of balanced translocation t (10; 11) (q 24; q 23) is presented. This female newborn showed no other malformation than hypoplastic left heart syndrome. According to several cases of 11q- and hypoplastic left heart in the literature and to this observation the authors postulate genes for left heart formation on chromosome 11q23.3.

Purification of maize pollen exines and analysis of associated proteins.

Zea mays (maize) pollen exines have been purified with the use of differential centrifugation and sucrose gradients, followed by mild detergent and high salt treatment. The final exine fraction is highly purified from other organelles and subcellular structures as assayed by transmission electron microscopy. Using mature maize pollen as the starting material, 0.2 to 0.3% of the total pollen protein remained associated with the exine fraction throughout the purification. Seven abundant sodium dodecyl sulfate-extractable proteins are detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the final fraction. Amino acid analysis reveals that one of the proteins contains a substantial amount of hydroxyproline, a characteristic of some primary cell wall proteins. The amino acid composition of the 25-kD protein strongly implies that it is an arabinogalactan protein. When exines are purified from earlier pollen developmental stages, a subset of the proteins found in the mature pollen exine is seen.

Phototoxicity, photoallergy, and contact sensitization of nitro musk perfume raw materials.

The potential of 4 related nitro musk substances (musk tibetene, musk ketone, musk xylol, and musk moskene) to cause photoallergy, phototoxicity, and/or contact sensitivity was compared to that of musk ambrette, a known photoallergen. Musk ambrette caused a high incidence of photoallergy as indicated by the severity of the skin grades as compared to a control group. Musk tibetene and musk moskene were negative for phototoxicity, photoallergenicity and contact sensitivity under the test conditions. Musk xylol was shown to be a weak contact sensitizer. Musk ketone gave challenge responses suggestive of a weak phototoxin and a weak contact sensitizer. The latter was not affected by light exposure. These data suggest that except for musk ambrette, the nitro musks as a group do not have the potential to produce photoallergy. Some members of this type of perfume raw material could be classified as weak sensitizers (musk xylol, musk ketone) or weakly phototoxic (musk ketone). These latter biological qualities have not been expressed clinically.

Use of the occlusive patch to evaluate the photosensitive properties of chemicals in guinea-pigs.

Guinea-pig tests were conducted on a known photocontact allergen, tetrachlorosalicylanilide (TCSA), a known phototoxin, 8-methoxypsoralen, two reportedly weak photoallergens, musk ambrette and 6-methylcoumarin, and a negative control, octylphenoxy polyethoxyethanol (Triton X-15). The data show that under the test conditions used, photosensitivity responses can be produced, and combinations of these as well as the other biological responses can be readily defined. The results indicate that musk ambrette is photoallergenic, that 8-methoxypsoralen is phototoxic and that Triton X-15 is only a slight irritant. On the other hand, results with TCSA suggest that it is a strong contact allergen and photoallergen, while 6-methylcoumarin would be considered to be a weak contact allergen with weak phototoxic properties. Previous reports that barrier destruction or adjuvanticity is necessary to produce photoallergy to musk ambrette were not confirmed; by ensuring occlusion using standard methods, the photoallergic nature of the response to this material was clearly demonstrated. A device described elsewhere (Newmann & Parker, Fd Chem. Toxic. 1985, 23, 683) has made it possible to develop methods that can be used to differentiate clearly among the possible biological responses that can occur in guinea-pigs when photoreactive materials are applied to their skin and irradiated. The probable biological responses that need to be defined, under the above conditions, are primary irritation, delayed contact hypersensitivity, phototoxicity and/or photoallergenicity.

A proposed plan for the detection and identification of potential sensitizers.

For toxicologists who are actively involved in safety testing and risk assessment, the ideal animal model should accurately predict the biologic response of humans after any contact with potentially hazardous materials. Unfortunately this goal is seldom, if ever, approached. Therefore, the toxicologist must design and execute experiments that will define to a higher degree of accuracy the inherent toxicity of the chemical and the biological response of the model. If the biologic response can be defined and understood and if the relevant information is available for comparable human responses, then the extrapolation to the human situation, although not always precise, can be made with a measure of assurance. Finally, and perhaps most importantly, it is essential that follow-up on human exposures be in sufficient detail so that the variations in biologic response can be further defined. In this way the precision and accuracy of the safety assessment can be checked.

Delayed contact hypersensitivity in the vagina and skin of the guinea pig.

A new method was developed to permit the contact of haptens exclusively with the vaginal mucosal surfaces of the guinea pig. The method described has some unique characteristics that make it potentially useful, not only for studies of the immune response but also for other areas of toxicologic concern. Utilizing this approach it was demonstrated that delayed contact hypersensitivity was as readily produced in the vagina as it was in the skin. Grossly, the vaginas of sensitized animals appeared normal when challenged with a non-irritating concentration of hapten but, histologically, a perivascular lymphocytic cuffing, that is the hallmark of the delayed hypersensitivity response, was demonstrated.