Functional Characterization of TetR-like Transcriptional Regulator PA3973 from Pseudomonas aeruginosa

Pseudomonas aeruginosa, a human opportunistic pathogen, is a common cause of nosocomial infections. Its ability to survive under different conditions relies on a complex regulatory network engaging transcriptional regulators controlling metabolic pathways and capabilities to efficiently use the available resources. P. aeruginosa PA3973 encodes an uncharacterized TetR family transcriptional regulator. In this study, we applied a transcriptome profiling (RNA-seq), genome-wide identification of binding sites using ChIP-seq, as well as the phenotype analyses to unravel the biological role of PA3973. Transcriptional profiling of P. aeruginosa PAO1161 overexpressing PA3973 showed changes in the mRNA level of 648 genes. Concomitantly, ChIP-seq analysis identified more than 300 PA3973 binding sites in the P. aeruginosa genome. A 13 bp sequence motif was indicated as the binding site of PA3973. The PA3973 regulon encompasses the PA3972-PA3971 genes encoding a probable acyl-CoA dehydrogenase and a thioesterase. In vitro analysis showed PA3973 binding to PA3973p. Accordingly, the lack of PA3973 triggered increased expression of PA3972 and PA3971. The DPA3972-71 PAO1161 strain demonstrated impaired growth in the presence of stress-inducing agents hydroxylamine or hydroxyurea, thus suggesting the role of PA3972-71 in pathogen survival upon stress. Overall our results showed that TetR-type transcriptional regulator PA3973 has multiple binding sites in the P. aeruginosa genome and influences the expression of diverse genes, including PA3972-PA3971, encoding proteins with a proposed role in stress response

Attitudes about Testicular Self-Examination among Polish Males

Introduction: Epidemiological data indicate an increased incidence of testicular cancer (TC), making it the most common malignant tumor in men from aged 15–45. Oncological and urological associations recommend that men with specific TC risk factors should regularly perform a testicular self-exam (TSE). The aim of the study was to discover the attitudes among Polish males regarding TSE and factors (environmental, social, educational) that affect intention to perform TSE. Methods: An original survey containing 21 questions was used to conduct a study among the Polish branch of VW (Volkswagen Poland) employees. Results: A total of 522 fully completed questionnaires were collected. The mean age of the surveyed respondents was 32 years. Information about TC and how to perform TSE was obtained by 34.4% (n = 185) of the men. It was shown that the following factors increase men’s intention to perform TSE: TC in their family member (p < 0.05; HR = 5.9; 95% CI: 1.5–23.0), GP’s(General Practitioner) recommendations (p < 0.001; HR = 6.8; 95% CI: 3.2–14.3), concern expressed by their partner (p < 0.001; HR = 3.3; 95% CI: 2.1–5.3), and social campaigns (p < 0.001; HR = 2.6; 95% CI: 1.5–4.6). Conclusions: Approximately half of young polish males do not perform TSE. Access to information on TC prevention is limited. Further action is needed to improve men’s awareness of TC and TSE

Pparγ1 Facilitates ErbB2-Mammary Adenocarcinoma in Mice

HER2, which is associated with clinically aggressive disease, is overexpressed in 15–20% of breast cancers (BC). The host immune system participates in the therapeutic response of HER2+ breast cancer. Identifying genetic programs that participate in ErbB2-induced tumors may provide the rational basis for co-extinction therapeutic approaches. Peroxisome proliferator-activated receptor γ (PPARγ), which is expressed in a variety of malignancies, governs biological functions through transcriptional programs. Herein, genetic deletion of endogenous Pparγ1 restrained mammary tumor progression, lipogenesis, and induced local mammary tumor macrophage infiltration, without affecting other tissue hematopoietic stem cell pools. Endogenous Pparγ1 induced expression of both an EphA2-Amphiregulin and an inflammatory INFγ and Cxcl5 signaling module, that was recapitulated in human breast cancer. Pparγ1 bound directly to growth promoting and proinflammatory target genes in the context of chromatin. We conclude Pparγ1 promotes ErbB2-induced tumor growth and inflammation and represents a relevant target for therapeutic coextinction. Herein, endogenous Pparγ1 promoted ErbB2-mediated mammary tumor onset and progression. PPARγ1 increased expression of an EGF-EphA2 receptor tyrosine kinase module and a cytokine/chemokine 1 transcriptional module. The induction of a pro-tumorigenic inflammatory state by Pparγ1 may provide the rationale for complementary coextinction programs in ErbB2 tumors