Surfactant protein B gene variations enhance susceptibility to squamous cell carcinoma of the lung in German patients

Genetic factors are thought to influence the risk for lung cancer. Since pulmonary surfactant mediates the response to inhaled carcinogenic substances, candidate genes may be among those coding for pulmonary surfactant proteins. In the present matched case–control study a polymorphism within intron 4 of the gene coding for surfactant specific protein B was analysed in 357 individuals. They were divided into 117 patients with lung cancer (40 patients with small cell lung cancer, 77 patients with non small cell lung cancer), matched controls and 123 healthy individuals. Surfactant protein B gene variants were analysed using specific PCR and cloned surfactant protein B sequences as controls. The frequency of the intron 4 variation was similar in both control groups (13.0% and 9.4%), whereas it was increased in the small cell lung cancer group (17.5%) and the non small cell lung cancer group (16.9%). The gene variation was found significantly more frequently in patients with squamous cell carcinoma (25.0%, P=0.016, odds ratio=3.2, 95%CI=1.24–8.28) than in the controls. These results indicate an association of the surfactant protein B intron 4 variants and/or its flanking loci with mechanisms that may enhance lung cancer susceptibility, especially to squamous cell carcinoma of the lung

Universal Stress Proteins Are Important for Oxidative and Acid Stress Resistance and Growth of Listeria monocytogenes EGD-e In Vitro and In Vivo

Background: Pathogenic bacteria maintain a multifaceted apparatus to resist damage caused by external stimuli. As part of this, the universal stress protein A (UspA) and its homologues, initially discovered in Escherichia coli K-12 were shown to possess an important role in stress resistance and growth in several bacterial species. Methods and Findings: We conducted a study to assess the role of three homologous proteins containing the UspA domain in the facultative intracellular human pathogen Listeria monocytogenes under different stress conditions. The growth properties of three UspA deletion mutants (deltalmo0515, deltalmo1580 and deltalmo2673) were examined either following challenge with a sublethal concentration of hydrogen peroxide or under acidic conditions. We also examined their ability for intracellular survival within murine macrophages. Virulence and growth of usp mutants were further characterized in invertebrate and vertebrate infection models. Tolerance to acidic stress was clearly reduced in Δlmo1580 and deltalmo0515, while oxidative stress dramatically diminished growth in all mutants. Survival within macrophages was significantly decreased in deltalmo1580 and deltalmo2673 as compared to the wild-type strain. Viability of infected Galleria mellonella larvae was markedly higher when injected with deltalmo1580 or deltalmo2673 as compared to wild-type strain inoculation, indicating impaired virulence of bacteria lacking these usp genes. Finally, we observed severely restricted growth of all chromosomal deletion mutants in mice livers and spleens as compared to the load of wild-type bacteria following infection. Conclusion: This work provides distinct evidence that universal stress proteins are strongly involved in listerial stress response and survival under both in vitro and in vivo growth conditions

Human TFIIIA alone is sufficient to prevent nucleosomal repression of a homologous 5S gene.

Plasmid DNA harbouring the human 5S rRNA gene was assembled into nucleosomes using either Xenopus S150 extracts or purified core histones in the presence of pectin. In both cases reconstitution of nucleosomes led to a complete repression of transcription. This repression could be efficiently counteracted by preincubating the template DNA with highly purified hTFIIIA which allowed the protein to bind to the ICR of the 5S gene. By using an efficient and well-defined in vitro reconstitution system based on isolated core histones in the presence of pectin, which is devoid of endogenous transcription factors, we demonstrate here for the first time that human TFIIIA alone is sufficient to prevent nucleosomal repression of h5S gene transcription and that additional pol III transcription factors are not required to achieve this effect. Additionally, we investigated the binding of hTFIIIA to a mononucleosome reconstituted on the human 5S gene. DNAse I footprinting experiments reveal that the entire ICR of the human 5S gene is covered by the nucleosome, thereby precluding the subsequent binding of human TFIIIA to the promoter of the 5S gene