Development, standardization and refinement of procedures for evaluating effects of endocrine active compounds on development and sexual differentiation of Xenopus laevis

Xenopus laevis has been introduced as a model to study effects of endocrine-active compounds (EAC) on development and sexual differentiation. However, variable and inconsistent data have raised questions about the reliability of the test methods applied. The current study was conducted in two laboratories to develop, refine, and standardize procedures and protocols. Larvae were exposed in flow-through systems to 17β-estradiol (E2), at concentrations from 0.2 to 6.0 μg E2 L−1 in Experiment 1A, and 0.015 to 2.0 μg E2 L−1 in Experiment 1B. In both studies survival (92%, 99%) and percentage of animals that completed metamorphosis (97%, 99%) indicated reproducible biological performance. Furthermore, minor variations in husbandry led to significant differences in snout-to-vent length, weight, and gonad size. In Experiment 1A, almost complete feminization occurred in all E2 treatment groups whereas a concentration response was observed in Experiment 1B resulting in an EC50 of 0.12 μg E2 L−1. The final verified protocol is suitable for determining effects of EAC on development and sexual differentiation in X. laevis

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Cyphenothrin Flea and Tick Squeeze-On for Dogs: Evaluation of Potential Health Risks Based on the Results of Observational Biological Monitoring

<div><p>An observational biomonitoring study was conducted involving adults and children in households that purchased and applied a cyphenothrin-containing spot-on product for dogs as part of their normal pet care practices. The 3- to 6-yr-old children had greater exposure than the adult applicators in the same house, 3.8 and 0.6 μg/kg body weight, respectively. The mean measured values in children were 13-fold lower than those estimated using the U.S. Environmental Protection Agency (EPA) current standard operating procedures (SOP) for pet products (assuming 5% dermal absorption), although the maximum absorbed dosage of one child on one day was equivalent to the default value derived from the SOPs. With regard to potential human health risks, it can be concluded that despite the inherent conservatism in both the exposure and toxicology data, the margins of exposure (MOE) were consistently greater than 100 for average, 95th percentile, and maximum exposures. More specifically, the results of this study demonstrated that the MOE were consistently greater than 1,000 for mean exposures and exceeded 100 for 95th percentile and maximum measured exposures, which clearly indicates a reasonable certainty of no harm when using the cyphenothrin spot-on products. It is also noteworthy that Sergeant’s spot-on products containing cyphenothrin currently sold in the United States have lower weight percentages of active ingredient and lower applied amounts than those used by all but two of the participant households in this study. </p></div