SummaryThe quorum sensing (QS) signalling system of Pseudomonas aeruginosa controls many important functions, including virulence. Although the production of the QS signal molecule N-3-oxo-dodecanoylhomoserine lactone (3OC12-HSL) is positively autoregulated, its concentration reaches a steady level long before stationary phase. The RsaL protein represses transcription of the lasI signal synthase gene, and thus reduces QS signal production. We show that RsaL binds simultaneously with LasR to the rsaL-lasI bidirectional promoter thereby preventing the LasR-dependent activation of both genes. In an rsaL mutant, 3OC12-HSL production continues to increase throughout growth. Thus RsaL provides homeostasis by functioning in opposition to LasR and limiting 3OC12-HSL production to a physiological concentration. Furthermore, transcription profiling revealed that RsaL regulates 130 genes independent of its effect on QS signal molecule production, including genes involved in virulence. We show that RsaL can repress pyocyanin and hydrogen cyanide virulence genes in two ways: directly, by binding to their promoters, and indirectly, by decreasing levels of the signals for their QS signal-dependent transcription. These investigations highlight the importance of RsaL as a global regulator of P. aeruginosa physiology that provides a counterbalance to 3OC 12-HSLdependent gene activation via multiple mechanisms.

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Objectives To evaluate the effect of spermatic vein ligation in patients over 30 years old and with lowgrade left varicocele, and thus help to establish whether such patients might bene®t from surgery. Patients and methods A randomized study was conducted on 68 infertile patients (30±38 years old) with evidence of sperm abnormalities and who had lowgrade varicocele (grade I according to Hirsch), comparing left spermatic vein ligation with no treatment. The outcome was assessed by standard sperm analysis and eventual paternity. Results There was no improvement in sperm quality in either of the groups one year after surgery, and no signi®cant difference in paternity. Conclusions Left spermatic vein ligation for low-grade varicocele in patients more than 30 years old cannot be recommended.

BackgroundSeveral promising biomarkers have been found for RCC, but none of them has been used in clinical practice for predicting tumour progression. The most widely used features for predicting tumour aggressiveness still remain the cancer stage, size and grade. Therefore, the aim of our study is to investigate the urinary peptidome to search and identify peptides whose concentrations in urine are linked to tumour growth measure and clinical data.MethodsA proteomic approach applied to ccRCC urinary peptidome (n = 117) based on prefractionation with activated magnetic beads followed by MALDI-TOF profiling was used. A systematic correlation study was performed on urinary peptide profiles obtained from MS analysis. Peptide identity was obtained by LC–ESI–MS/MS.ResultsFifteen, twenty-six and five peptides showed a statistically significant alteration of their urinary concentration according to tumour size, pT and grade, respectively. Furthermore, 15 and 9 signals were observed to have urinary levels statistically modified in patients at different pT or grade values, even at very early stages. Among them, C1RL, A1AGx, ZAG2G, PGBM, MMP23, GP162, ADA19, G3P, RSPH3, DREB, NOTC2 SAFB2 and CC168 were identified.ConclusionsWe identified several peptides whose urinary abundance varied according to tumour size, stage and grade. Among them, several play a possible role in tumorigenesis, progression and aggressiveness. These results could be a useful starting point for future studies aimed at verifying their possible use in the managements of RCC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0693-8) contains supplementary material, which is available to authorized users.