A public health context for residual risk assessment and risk management under the clean air act

The 1990 amendments to the Clean Air Act required the EPA to institute new pollution control technology requirements for industrial sources of air pollution. In part because agreement could not be reached on the best way for the EPA to determine whether any significant risks to human health will remain after the technology controls are in place, the amendments also created a Commission on Risk Assessment and Risk Management and gave the commission a broad mandate to review and make recommendations concerning risk assessment and risk management in federal regulatory programs. In its March 1997 final report to Congress and the administration, the commission recommended a tiered approach to assessing such residual risks. That approach included the idea that when decisions about managing residual risks are made, emissions should be evaluated in the context of other sources of air pollution. Evaluating risks in their larger contexts is consistent with what the commission called a public health approach to environmental risk management. This paper describes the public health approach and how it applies to evaluating residual risks under the Clean Air Act.     

Is sperm galactosyltransferase a signaling subunit of a multimeric gamete receptor?

The influence of relatedness on the pre- and post-emergent survival of honey bee queens was investigated. Workers did not preferentially rear sisters over non-siblings under conditions of natural queen replacement. After queen emergence, however, there was a significant effect of a queen's relatedness to the workers on her survivorship during fights with rival queens. The mechanism of this bias towards related queens is unknown, and several hypotheses are discussed. The difference in post-emergent survivability suggests that kin selection may operate during competition among adult queens at this crucial stage of honey bee reproduction. Copyright 1998 The Association for the Study of Animal Behaviour Copyright 1998 The Association for the Study of Animal Behaviour.     

Use of protein A gene fusions for the analysis of structure-function relationship of the transactivator protein C of bacteriophage Mu

A sensitive dimerization assay for DNA binding proteins has been developed using gene fusion technology. For this purpose, we have engineered a gene fusion using protein A gene of Staphylococcus aureus and C gene, the late gene transactivator of bacteriophage Mu. The C gene was fused to the 3' end of the gene for protein A to generate an A- C fusion. The overexpressed fusion protein was purified in a single step using immunoglobulin affinity chromatography. Purified fusion protein exhibits DNA binding activity as demonstrated by electrophoretic mobility shift assays. When the fusion protein A-C was mixed with C and analyzed for DNA binding, in addition to C and A-C specific complexes, a single intermediate complex comprising of a heterodimer of C and A-C fusion proteins was observed. Further, the protein A moiety in the fusion protein A-C does not contribute to DNA binding as demonstrated by proteolytic cleavage and circular dichroism (CD) analysis. The assay has also been applied to analyze the DNA binding domain of C protein by generating fusions between protein A and N- and C-terminal deletion mutants of C. The results indicate a role for the region towards the carboxy terminal of the protein in DNA binding. The general applicability of this method is discussed.      

Solution structure and basis for functional activity of stromal cell-derived factor-1; dissociation of CXCR4 activation from binding and inhibition of HIV-1

The three-dimensional structure of stromal cell-derived factor-1 (SDF-1) was determined by NMR spectroscopy. SDF-1 is a monomer with a disordered N-terminal region (residues 1-8), and differs from other chemokines in the packing of the hydrophobic core and surface charge distribution. Results with analogs showed that the N-terminal eight residues formed an important receptor binding site; however, only Lys-1 and Pro-2 were directly involved in receptor activation. Modification to Lys-1 and/or Pro-2 resulted in loss of activity, but generated potent SDF-1 antagonists. Residues 12-17 of the loop region, which we term the RFFESH motif, unlike the N-terminal region, were well defined in the SDF-1 structure. The RFFESH formed a receptor binding site, which we propose to be an important initial docking site of SDF-1 with its receptor. The ability of the SDF-1 analogs to block HIV-1 entry via CXCR4, which is a HIV-1 coreceptor for the virus in addition to being the receptor for SDF-1, correlated with their affinity for CXCR4. Activation of the receptor is not required for HIV-1 inhibition.     

Six patients with oral-facial-digital syndrome IV: the case for heterogeneity

The oral-facial-digital syndromes (OFDS) have in common minor facial and oral anomalies (including tongue lobulation and/ or hamartomas, accessory frenula, and alveolar anomalies) and variable digital defects such as polydactyly. The classification based on the presence of additional findings [Toriello, 1988, 1993] is not perfect, as many reported examples of a particular OFDS have some other condition. Here we describe six children, all diagnosed as having OFDS IV (OFDS with tibial defects), whose manifestations illustrate the apparent genetic heterogeneity.     

Darier''s disease: severe eczematization successfully treated with cyclosporin

A novel calcitonin (CT) was isolated from the spotlined sardine, Sardinops melanostictus. The primary structure of sardine CT was determined as follows: H-Cys-Ser-Asn-Leu-Ser-Thr- Cys-Ala-Leu-Gly-Lys-Leu-Ser-Gln-Glu-Leu-His-Lys-Leu-Gln-Ser-Tyr-Pro-Arg- Thr- Asn-Val-Gly-Ala-Gly-Thr-Pro-NH2. This amino acid sequence was different from that of salmon CT in 4 amino acid residues at positions 8th, 21th, 27th and 29th. As judged by the international method of CT bioassay, hypocalcemic activity of sardine CT was calculated as 4156 IU/mg. When compared for durability of CTs, it was found that sardine CT was significantly more potent than that of salmon CT. This is the first report of CT from a marine species of teleost.