Novel target genes of PsrA transcriptional regulator of Pseudomonas aeruginosa

The PsrA transcriptional regulator is involved in stationary phase induced transcriptional regulation of rpoS and in negative auto-regulation in Pseudomonas aeruginosa. This study was designed to determine whether other loci were regulated by PsrA in P. aeruginosa. Computer search was performed of the PsrA binding motif (G/CAAAC N2-4 GTTTG/C) against the P. aeruginosa genome sequence. Four of 14 analysed promoters responded to and bound PsrA; (i) divergent promoters controlling PA2952/ PA2951 and PA2953, (ii) promoter of PA0506 and (iii) upstream region of PA3571. Promoters PA0506 and PA2952-PA2951 were regulated negatively whereas promoters of PA2953 and PA3571 were regulated positively by PsrA. Two dimensional sodium dodecyl sulphate polyacrylamide gel electrophoresis (21) SDS-PAGE) analysis on total proteins from P. aeruginosa PAO1 and psrA knock-out derivative was also performed resulting in the identification of 11 protein spots which were differentially regulated. These studies have indicated PsrA as a global regulator

HCV IRES manipulates the ribosome to promote the switch from translation initiation to elongation.

The internal ribosome entry site (IRES) of the hepatitis C virus (HCV) drives noncanonical initiation of protein synthesis necessary for viral replication. Functional studies of the HCV IRES have focused on 80S ribosome formation but have not explored its role after the 80S ribosome is poised at the start codon. Here, we report that mutations of an IRES domain that docks in the 40S subunit's decoding groove cause only a local perturbation in IRES structure and result in conformational changes in the IRES-rabbit 40S subunit complex. Functionally, the mutations decrease IRES activity by inhibiting the first ribosomal translocation event, and modeling results suggest that this effect occurs through an interaction with a single ribosomal protein. The ability of the HCV IRES to manipulate the ribosome provides insight into how the ribosome's structure and function can be altered by bound RNAs, including those derived from cellular invaders

Expression of the progenitor marker NG2/CSPG4 predicts poor survival and resistance to ionising radiation in glioblastoma

Glioblastoma (GBM) is a highly aggressive brain tumour, where patients respond poorly to radiotherapy and exhibit dismal survival outcomes. The mechanisms of radioresistance are not completely understood. However, cancer cells with an immature stem-like phenotype are hypothesised to play a role in radioresistance. Since the progenitor marker neuron-glial-2 (NG2) has been shown to regulate several aspects of GBM progression in experimental systems, we hypothesised that its expression would influence the survival of GBM patients. Quantification of NG2 expression in 74 GBM biopsies from newly diagnosed and untreated patients revealed that 50% express high NG2 levels on tumour cells and associated vessels, being associated with significantly shorter survival. This effect was independent of age at diagnosis, treatment received and hypermethylation of the O6-methylguanine methyltransferase (MGMT) DNA repair gene promoter. NG2 was frequently co-expressed with nestin and vimentin but rarely with CD133 and the NG2 positive tumour cells harboured genetic aberrations typical for GBM. 2D proteomics of 11 randomly selected biopsies revealed upregulation of an antioxidant, peroxiredoxin-1 (PRDX-1), in the shortest surviving patients. Expression of PRDX-1 was associated with significantly reduced products of oxidative stress. Furthermore, NG2 expressing GBM cells showed resistance to ionising radiation (IR), rapidly recognised DNA damage and effectuated cell cycle checkpoint signalling. PRDX-1 knockdown transiently slowed tumour growth rates and sensitised them to IR in vivo. Our data establish NG2 as an important prognostic factor for GBM patient survival, by mediating resistance to radiotherapy through induction of ROS scavenging enzymes and preferential DNA damage signalling

Evaluación de la frecuencia cardíaca y su relación con el remodelado ventricular en respuesta al ejercicio dinámico como indicador de función autonómica en atletas, pesistas y maratonistas

Se estudiaron 113 sujetos (atletas maratonistas, atletas pesistas y controles sedentarios sanos) a los que se les realizó una prueba de esfuerzo en banda sin fin, para evaluar la reserva vagal, definida por la aceleración de la frecuencia cardiaca (FC) a los 10 segundos de iniciado el ejercicio, como la recuperación de la FC al primer minuto y el segundo minuto después de la realización del ejercicio dinámico, Δ1 y Δ2 respectivamente. Se realizó ecocardiograma transtoraxico para evaluar los índices de volúmenes ventriculares y la función diastólica, para determinar los patrones de llenado ventricular. La muestra se dividió en tres grupos: Grupo I: Control de Sedentarios Sanos, Grupo II: Maratonistas, Grupo III: Pesistas. Se observó que el Grupo II mostro mayor recuperación de la FC con un Δ1 de m=36±14 lat/min y Δ2 de m=58±15 lat/min, con mayor predominio vagal; asociado con un patrón geométrico ventricular izquierdo (VI) de mayores volúmenes indexados del VI de m= 63±82 mm con una p 0,0001 con relación a los del Grupo I y Grupo III. El Grupo III mostró menor recuperación de la FC con respecto a los demás grupos y mayor índice de la relación E/e’ (m=8±3), p 0,0001. Por lo tanto, este estudio nos permite concluir que los atletas mostraron un tono vagal aumentado y una menor rigidez VI con respecto a atletas estáticos y plantea los posibles mecanismos que explican este fenómeno

Evaluación de la frecuencia cardíaca y su relación con el remodelado ventricular en respuesta al ejercicio dinámico como indicador de función autonómica en atletas, pesistas y maratonistas

This study was performed to evaluate 118 subjects (athlete’s runners, weight lifters, with control group of healthy subjects sedentary) who have performed stress with treadmill test to evaluate the vagal reserve, as the grade of acceleration of the heart rate (HR) after the 10 second of starting the exercise and the Δ1 and Δ2 respectively,. Transtoracic echocardiography was performed to evaluate diameters and ventricular volumes and diastolic function to determine the patterns of ventricular filling. The sample was divided into three groups: Group I Sedentary, Group II Runners, and the Group III Weight Lifters. Group II was those with vagal predominance in the test with a Δ1 de m=36±14 lat/min and Δ2 de m=58±15 lat/min (p0.0001 and expressed left ventricular (LV) geometric patterns given by higher LV diameter and higher volumes indexed (m= 63±82 mm) p 0.0001 in relation to the group I and III. On the other hand, the weight lifters expressed the less HR recovery after the exercise and the higher wall thickness and higher relation E/e (m=8±3). p0.0001. This study allows us to affirm on the vagal predominance and less stiffness, was observed in endurance athletes, compared to athlete’s static and also allows opening a light to the explanation of the possible reasons to elucidate this phenomenon.Se estudiaron 113 sujetos (atletas maratonistas, atletas pesistas y controles sedentarios sanos) a los que se les realizó una prueba de esfuerzo en banda sin fin, para evaluar la reserva vagal, definida por la aceleración de la frecuencia cardiaca (FC) a los 10 segundos de iniciado el ejercicio, como la recuperación de la FC al primer minuto y el segundo minuto después de la realización del ejercicio dinámico, Δ1 y Δ2 respectivamente. Se realizó ecocardiograma transtoraxico para evaluar los índices de volúmenes ventriculares y la función diastólica, para determinar los patrones de llenado ventricular. La muestra se dividió en tres grupos: Grupo I: Control de Sedentarios Sanos, Grupo II: Maratonistas, Grupo III: Pesistas. Se observó que el Grupo II mostro mayor recuperación de la FC con un Δ1 de m=36±14 lat/min y Δ2 de m=58±15 lat/min, con mayor predominio vagal; asociado con un patrón geométrico ventricular izquierdo (VI) de mayores volúmenes indexados del VI de m= 63±82 mm con una p 0,0001 con relación a los del Grupo I y Grupo III. El Grupo III mostró menor recuperación de la FC con respecto a los demás grupos y mayor índice de la relación E/e’ (m=8±3), p 0,0001. Por lo tanto, este estudio nos permite concluir que los atletas mostraron un tono vagal aumentado y una menor rigidez VI con respecto a atletas estáticos y plantea los posibles mecanismos que explican este fenómeno