Strand displacement of double-stranded DNA by triplex-forming antiparallel purine-hairpins

We characterize the binding affinity and the thermodynamics of hybridization of triplex-forming antiparallel purine-hairpins composed of two antiparallel purine domains linked by a loop directed toward single-stranded and double-stranded DNA (ssDNA, dsDNA). Gel retardation assays and melting experiments reveal that a 13-mer purine-hairpin binds specifically and with a Kd of 8 × 10-8 M to polypyrimidine ssDNA to form a triple helical structure. Remarkably, we show that purine-hairpins also bind polypurine/polypyrimidine stretches included in a dsDNA of several hundred bp in length. Binding of purine-hairpins to dsDNA occurs by triplex formation with the polypyrimidine strand, causing displacement of the polypurine strand. Because triplex formation is restricted to polypurine/polypyrimidine stretches of dsDNA, we studied the triplex formation between purine-hairpins and polypyrimidine targets containing purine interruptions. We found that an 11-mer purine-hairpin with an adenine opposite to a guanine interruption in the polypyrimidine track binds to ssDNA and dsDNA, allowing expansion of the possible target sites and increase in the length of purine-hairpins. Thus, when using a 20-mer purine-hairpin targeting an interruption-containing polypyrimidine target, the binding affinity is increased compared to its 13-mer antiparallel purine-hairpin counterpart. Surprisingly, this increase is much more pronounced than that observed for a tail-clamp purine-hairpin extended up to 20 nt in the Watson-Crick domain only. Thus, triplex-forming antiparallel purine-hairpins can be a potentially useful strategy for both single-strand and double-strand nucleic acid recognition.This research was supported by grants SAF02-0363 and SAF05-0247 from the “Comisión Interministerial de Ciencia y Tecnología” and 2001SGR141 from the “Comissionat d’Universitats i Recerca (CUR)”. S.C. is the recipient of a postgraduate fellowship from the Spanish Ministry of Education. We thank Jordi Robles from University of Barcelona for his help with the use of MeltWin software.Peer reviewe

Leakage Subspace Precoding and Scheduling for Physical Layer Security in Multi-User XL-MIMO Systems

We investigate the achievable secrecy sum-rate in a multi-user XL-MIMO system, on which user distances to the base station become comparable to the antenna array dimensions. We show that the consideration of spherical-wavefront propagation inherent to these set-ups is beneficial for physical-layer security, as it provides immunity against eavesdroppers located in similar angular directions that would otherwise prevent secure communication under classical planar-wavefront propagation. A leakage subspace precoding strategy is also proposed for joint secure precoding and user scheduling, which allows to improve the secrecy sum-rate compared to conventional zero-forcing based strategies, under different eavesdropper collusion strategies.Comment: 5 pages and 4 figures. This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessibl

Simultaneous H.E.S.S. and RXTE observations of the microquasars GRS 1915+105, Circinus X-1 and V4641 Sgr

Microquasars, Galactic binary systems showing extended and variable radio emission, are potential gamma-ray emitters. Indications of gamma-ray transient episodes have been reported in at least two systems, Cyg X-1 and Cyg X-3. The identification of additional gamma-ray emitting microquasars is key for a better understanding of these systems. Very-high-energy gamma-ray emission from microquasars has been predicted to happen during periods of transient outbursts potentially connected with the formation of a jet-like outflow. Contemporaneous observations using the H.E.S.S. telescope array and the RXTE satellite were obtained on three microquasars: GRS 1915+105, Circinus X-1 and V4641 Sgr with the aim of detecting a broadband flaring event in the very-high-energy gamma-ray and X-ray bands. We report here on the analysis of these data for each system, including a detailed X-ray analysis assessing the location of the sources in a hardness-intensity diagram during the observations. Finally we discuss the derived upper limits on their very-high-energy gamma-ray flux

Estudio ecocardiográfico y de la concentración de NT-proBNP en pacientes diabéticos tipo 2 con y sin cardiopatía isquémica

The aim of this study was to determine whether there are differences in echocardiographic findings or in the level of a biochemical marker (i.e. N-terminal probrain natriuretic peptide [NT-proBNP]) between controls and type-2 diabetic patients with or without ischemic heart disease. Echocardiography was used to assess left ventricular function and morphology. In addition, the plasma NT-proBNP concentration was measured. The prevalence of diastolic dysfunction was greater in diabetics without ischemic heart disease than in controls (88% vs. 74%, respectively; P< .001) and the NT-proBNP concentration was higher (350.6+/-197.8 vs. 281.7+/-190.4 fmol/mL; P< .001). Diabetics with ischemic heart disease had a higher NT-proBNP concentration than those without (720.4+/-278.1 vs. 350.6+/-197.8 fmol/mL, respectively; P< .001). An NT-proBNP concentration >490 fmol/mL had a sensitivity of 84% and a specificity of 75% for detecting ischemic heart disease in diabetics

A case of capecitabine-induced coronary microspasm in a patient with rectal cancer

5-Fluorouracil (5-FU) is the most frequently used chemotherapy agent concomitant with radiotherapy in the management of patients with rectal cancer. Capecitabine is an oral fluoropyrimidine that mimics the pharmaconkinetics of infusional 5-FU. This new drug is replacing 5-FU as a part of the combined-modality treatment of a number of gastrointestinal cancers. While cardiac events associated with the use of 5-FU are a well known side effect, capecitabine-induced cardiotoxicity has been only rarely reported. Here, we reviewed the case of a patient with rectal cancer who had a capecitabine-induced coronary vasospasm. The most prominent mutation of the dihydropyrimidine dehydrogenase gene was also analyzed

Effect of maternal feed intake during mid-gestation on pig performance, meat quality and muscle fiber development

Increasing feed allowance during gestation has been related with changes in muscle fiber development and pig performance post-natally, affecting meat quality traits at slaughter