Many genes involved in Drosophila melanogaster innate immune processes have been identified, but whether naturally occurring polymorphism in these genes leads to variation in immune competence among wild flies has not been tested. We report here substantial variability among wild-derived D. melanogaster in the ability to suppress infection by a Gram-negative entomopathogen, Serratia marcescens. Variability in immune competence was significantly associated with nucleotide polymorphism in 16 innate immunity genes, corresponding primarily to pathogen recognition and intracellular signaling loci, and substantial epistasis was detected between intracellular signaling and antimicrobial peptide genes. Variation in these genes, therefore, seems to drive variability in immunocompetence among wild Drosophila.
Maturation promoting factor (MPF), a complex of cyclin-dependent kinase 1 and cyclin B, drives oocyte maturation in all animals. Mechanisms to block MPF activation in developing oocytes must exist to prevent precocious cell cycle progression prior to oocyte maturation and fertilization. This study sought to determine the developmental consequences of precociously activating MPF in oocytes prior to fertilization. Whereas depletion of Myt1 in Xenopus oocytes causes nuclear envelope breakdown in vitro, we found that depletion of the Myt1 ortholog WEE-1.3 in C. elegans hermaphrodites causes precocious oocyte maturation in vivo. Although such oocytes are ovulated, they are fertilization incompetent. We have also observed novel phenotypes in these precociously maturing oocytes, such as chromosome coalescence, aberrant meiotic spindle organization, and the expression of a meiosis II postfertilization marker. Furthermore, co-depletion studies of CDK-1 and WEE-1.3 demonstrate that WEE-1.3 is dispensable in the absence of CDK-1, suggesting that CDK-1 is a major target of WEE-1.3 in C. elegans oocytes.
Mesothelioma rates are declining toward background levels, although estimates of the background rate have varied. We expanded upon earlier analyses and provided a data-based estimate of the background rate. We analyzed US male and female patterns for five age groups using the National Cancer Institute's Surveillance Epidemiology and End Results registry data from 1973 to 2002. Age-specific and age-adjusted incidence rates per 1 000 000 persons per year, standardized to the 2000 US population, were calculated for total, pleural, and peritoneal mesothelioma. We also calculated rates for persons who attained working age after the US Occupational Safety and Health Administration asbestos exposure limits took effect. Mesothelioma rates observed among young males and females varied little over time. We observed a decline and convergence of recent male and female rates in older age groups, except those who are between the age of 60 and above, for whom the 2002 male rate was approximately five times greater than that of females. As expected, rates were higher in major shipyard areas on the West coast. Rates for persons with little or no opportunity for occupational asbestos exposure were 1.15 (95% confidence interval: 0.90-1.45) for men and 0.94 (95% confidence interval: 0.87-1.24) for women. Mesothelioma is rare in younger age groups, and rates have been relatively stable and similar for both sexes. Rates continue to decline in older age groups, but remain high for males at 60 years or older. Rates among females at older ages suggest an impact of occupational exposure. The background rate for persons below age 50 is approximately one per million, independent of sex. Future data are needed to estimate this rate for older age groups.
BACKGROUNDIonizing radiation has been used since the 1950s to treat a variety of cancers. Cancer patients who are treated with radiotherapy have shown increased risks for a variety of second malignancies, including mesothelioma, in several recent reports. The only existing study of Hodgkin lymphoma (HL) and subsequent mesothelioma had a short observation period.METHODSThe authors used Surveillance, Epidemiology, and End Results data over a 30‐year period to identify patients with HL and non‐Hodgkin lymphoma (NHL) who also were diagnosed with mesothelioma. Standardized incidence ratios (SIR) and absolute excess risks were calculated by sex and treatment modality for both types of lymphoma.RESULTSTwenty‐six patients were identified who had mesothelioma as second primaries based on 21,881 diagnoses of HL and 101,001 diagnoses of NHL. There was a statistically significant increase in mesothelioma (4 diagnoses; SIR, 6.59; 95% confidence interval [95% CI], 1.79–16.87) among men with HL who received radiation, but no women survivors were identified who had a diagnosis of mesothelioma. For NHL survivors, there was a nonsignificant excess of mesothelioma among men (SIR, 1.91; 95% CI, 0.77–3.93) and women (SIR, 3.75; 95% CI, 0.77–10.95) who had received radiation treatment. There were no increases among patients who were unirradiated.CONCLUSIONSMesothelioma rates for patients who had received radiotherapy were increased for survivors of HL and NHL. No increases were observed among the unirradiated. These findings and the existing body of supporting studies confirmed that radiotherapy is a cause of mesothelioma. Cancer 2007. © 2007 American Cancer Society.
Genome-scale studies of population structure and high-resolution mapping of genetically complex traits both require techniques for accurately and efficiently genotyping large numbers of polymorphic sites in multiple individuals. Many high-throughput genotyping technologies require the purchase of expensive equipment or consumables and are therefore out of reach of some individual research laboratories. Conversely, less expensive technologies are often labor intensive so that the effort involved in typing large numbers of samples or polymorphic sites is prohibitive. Here we present a method of fluorescently post-labeling restriction digestion using standard dye-terminator sequencing chemistry so that RFLP and AFLP products can be visualized on an automated sequencer. This labeling method is efficient, inexpensive, easily multiplexed, and requires no unusual equipment or reagents, thus striking a balance between cost and throughput that should be appropriate for many research groups and core facilities.
Genome-scale studies of population structure and high-resolution mapping of genetically complex traits both require techniques for accurately and efficiently genotyping large numbers of polymorphic sites in multiple individuals. Many high-throughput genotyping technologies require the purchase of expensive equipment or consumables and are therefore out of reach of some individual research laboratories. Conversely, less expensive technologies are often labor intensive so that the effort involved in typing large numbers of samples or polymorphic sites is prohibitive. Here we present a method of fluorescently post-labeling restriction digestion using standard dye-terminator sequencing chemistry so that RFLP and AFLP products can be visualized on an automated sequencer. This labeling method is efficient, inexpensive, easily multiplexed, and requires no unusual equipment or reagents, thus striking a balance between cost and throughput that should be appropriate for many research groups and core facilities.
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