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DIR Papers of the Month

By Eddy Ball
January 2007

Indoor Fungus Exposure Linked to Asthma

In a study funded by NIEHS and the U.S. Department of Housing and Urban Development, an interdisciplinary team of DIR and Constella Group researchers found a significant association between indoor exposure to allergens from the fungus Alternaria alternata and asthma symptoms in a nationally representative sample of U.S. homes.

The data are from the National Survey of Lead and Allergens in Housing (NSLAH), a cross-sectional survey of 831 housing units inhabited by 2,456 individuals, 26% of them children, in 75 different U.S. locations. It was the first population-based study to examine the health effects of allergenic components of Alternaria using a polyclonal anti-Alternata antibody assay. The team of investigators showed that the prevalence of current asthma increased with higher Alternaria allergen levels, likely in an exposure-dependent manner. Residents in homes with high concentrations of Alternaria allergen were 1.84 times more likely to have current asthma than residents in homes with low concentrations of the allergen.

This study provides new information on Alternaria exposures in relation to asthma symptoms. Because the health impact of indoor fungal exposures has not been studied as extensively as outdoor exposures, the study also underscores the importance of preventing mold and moisture-related problems and having homes cleaned on a regular basis.

Citation: Salo PM, Arbes SJ Jr, Sever M, Jaramillo R, Cohn RD, London SJ, Zeldin DC. 2006. Exposure to Alternaria alternata in US homes is associated with asthma symptoms. J Allergy Clin Immunol 118(4):892-898.

Fidelity of DNA Synthesis by Yeast Polymerase Delta

In an NIEHS-funded study published in Nucleic Acids Research, a team of investigators reports on the effects of accessory proteins on the fidelity of DNA synthesis by yeast polymerase delta (pol d) in vitro.

The investigators examined the error rates of DNA replication and repair by pol d alone and in combination with the single-stranded DNA-binding protein complex replication protein A (RPA) and/or the processivity clamp proliferating cell nuclear antigen (PCNA) and its loader replication factor C (RFC). The results indicate that fidelity for errors involving single base pairs is largely determined by pol d itself. However, investigators determined that the accessory proteins strongly modulated the ability of pol d to delete large numbers of nucleotides between directly repeated sequences. In the presence of either RPA or PCNA the error rate was reduced by approximately 10-fold and by a rate equal to or more than 90-fold in the presence of both.

This research points to the importance of PCNA and RPA in protecting the genomes of higher plants and animals against the biological consequences of large deletions, with possible implications in regard to instabilities associated with hereditary degenerative diseases.

Citation: Fortune JM, Stith CM, Kissling GE, Burgers PM, Kunkel TA. 2006. RPA and PCNA suppress formation of large deletion errors by yeast DNA polymerase delta. Nucleic Acids Res 34(16):4335-4341.

Genetic Modification Proposed to Combat "Phosphate Crisis"

NIEHS intramural researchers, collaborating with researchers from the University of Pittsburg and North Carolina State University, have demonstrated that an avian phytase may help poultry, pigs and other monogastric production animals release phosphate from the phytic acid (InsP6) in their feed.

Researchers determined that rat and human recombinant "phytase," multiple inositol polyphosphate phosphatase (MINPP), hydrolyzed InsP6 at the very slow rate of 6nmol/mg protein per minute. The recombinant avian MINPP, in contrast, was 100-fold more efficient as a phytase. The study's results raise the possibility that a genetically-modified chicken that secreted MINPP into the digestive tract may digest InsP6 effectively in vivo. The researchers also used an avian model cell line to demonstrate how MINPP could be modified to ensure it is secreted.

This research points to the potential of a strain of genetically-modified chickens for addressing the current "phosphate crisis." Such production animals could help to conserve the planet's diminishing phosphate reserves and reduce pollution by decreasing phosphate levels in manure. Avian MINPP is predicted to perform as well as microbial phytases, and its expression in animals is less expensive and potentially safer for farm workers than using phytase as a feed additive.

Citation: Cho J, Choi K, Darden T, Reynolds PR, Petitte JN, Shears SB. 2006. Avian multiple inositol polyphosphate phosphatase is an active phytase that can be engineered to help ameliorate the planet's "phosphate crisis." J Biotechnol 126(2):248-259.

Depression and Pesticide Exposure in Female Farm Spouses

In a study funded by the NIH Intramural Research Program, National Cancer Institute and NIEHS, researchers used questionnaire data from the Agricultural Health Study (AHS) to evaluate the relationship of reported depression to pesticide exposure among ~29,000 female spouses of licensed pesticide applicators, mainly farmers.

The researchers used data from questionnaires completed at enrollment in the AHS (1993-1997). The researchers defined cases as respondents reporting a physician diagnosis of depression requiring medication (N=2,051). Controls were respondents who did not have doctor-diagnosed depression. Lifetime pesticide use was categorized as never used pesticides, low exposure as up to 225 lifetime days, and high exposure as more than 225 days and a history of diagnosed pesticide poisoning.

The team found that a history of pesticide poisoning was associated with a more than three-fold increase in risk of self-reported, physician-diagnosed depression among female spouses of licensed pesticide applicators. Pesticide use in the absence of poisoning had little effect. Non-pesticide risk factors for depression included age, health status, smoking, frequent alcohol use, and working a job off the farm. "This study highlights the importance of preventing pesticide poisoning because the chronic effects of those poisonings may contribute to high rates of depression," the authors concluded.

Citation: Beseler C, Stallones L, Hoppin JA, Alavanja MC, Blair A, Keefe T, Kamel F. 2006. Depression and pesticide exposures in female spouses of licensed pesticide applicators in the agricultural health study cohort. J Occup Environ Med 48(10):1005-1013.



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