The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma

We are grateful to Paulo Vieira, Cecília Leão, Manuel T. Silva, Nuno Sousa, Jorge Correia- Pinto, Joana Palha, Margarida Correia-Neves, Margarida Lima and Matthew Berry for all their input throughout these studies and critical reading of the manuscript. We are grateful to the patients who joint this study as well as to all members of the Life and Health Sciences Research Institute and School of Health Sciences, University of Minho, who contributed in any way to the development of this workNon-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case-control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P=7.3E-9) and Italian (OR, 1.84; P=6.0E-5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner.AC, NSO, MTC, and AJA were financially supported by a fellowship from Fundação para a Ciência e Tecnologia, Portugal. MS is a Ciência 2007 fellow. This study was supported by Fundação para a Ciência e Tecnologia, Portugal (PIC/IC/83313/2007) and by Fundação Calouste Gulbenkian, Serviço de Saúde e Desenvolvimento Humano, Portugal (Grant Number:Proc/60666-MM/734). CFS, PB and LC were supported by National Institutes of Health (NIH) grants CA122663 and CA104682, and PB also by NIH grants CA45614 and CA89745

Comprehensive genetic assessment of a functional TLR9 promoter polymorphism: no replicable association with asthma or asthma-related phenotypes

<p>Abstract</p> <p>Background</p> <p>Prior studies suggest a role for a variant (rs5743836) in the promoter of toll-like receptor 9 (TLR9) in asthma and other inflammatory diseases. We performed detailed genetic association studies of the functional variant rs5743836 with asthma susceptibility and asthma-related phenotypes in three independent cohorts.</p> <p>Methods</p> <p>rs5743836 was genotyped in two family-based cohorts of children with asthma and a case-control study of adult asthmatics. Association analyses were performed using chi square, family-based and population-based testing. A luciferase assay was performed to investigate whether rs5743836 genotype influences TLR9 promoter activity.</p> <p>Results</p> <p>Contrary to prior reports, rs5743836 was not associated with asthma in any of the three cohorts. Marginally significant associations were found with FEV₁and FVC (p = 0.003 and p = 0.008, respectively) in one of the family-based cohorts, but these associations were not significant after correcting for multiple comparisons. Higher promoter activity of the CC genotype was demonstrated by luciferase assay, confirming the functional importance of this variant.</p> <p>Conclusion</p> <p>Although rs5743836 confers regulatory effects on TLR9 transcription, this variant does not appear to be an important asthma-susceptibility locus.</p

Protein hydrolysates as resistance inducers for controlling Green Mould of citrus fruits

The effectiveness of eight protein hydrolysates of natural origin (soybean, lupin, pea, yeast, casein, and malt hydrolysate) for controlling Penicillium digitatum, the main postharvest pathogen of citrus fruit, was evaluated by both in vitro and in vivo trials. The in vitro screening showed no significant effect of the different compounds on pathogen radial growth, whereas the application of the different protein hydrolysates (1.6 mg/ml) to wounded fruits proved their ability to induce resistance against P. digitatum by reducing significantly disease incidence and severity. The best activity was observed on fruits treated with soybean, lupin, and casein hydrolysates. Although further studies are needed, the results obtained are encouraging and potential application against green mould on citrus fruit is foreseen

Synthesis of Fe-doped TiO2 with improved photocatalytic properties under Vis-L irradiation.

Fe-doped TiO2 nanoparticles were successfully synthesized by the coprecipitation method. TiO2 was doped with a different molar ratio of iron amounts, namely 0.1% and 0.2%. An undoped TiO2 was also prepared for comparison. X-ray diffraction (XRD), transmission electron microscopy (TEM) and UV-visible diffuse reflectance spectroscopy techniques were used to characterize the as-synthesized nanoparticles. The XRD spectra revealed that the photocatalysts were mostly in a well-crystallized anatase phase. Optical properties of the powders shifted from UV to the beginning of the visible light (Vis-L) region. Absorption edge wavelengths between 392 and 380 nm were obtained for the Fe-doped TiO2 and TiO2-P25, corresponding to band gap energies between 3.17 and 3.26 eV. TEM images showed homogeneity with a certain degree of agglomeration for all the samples. The photocatalytic efficiency of the as-synthesized Fe-doped TiO2 nanoparticles was performed using azo dye methyl orange (MO) in an aqueous solution under Vis-L irradiation. The photocatalytic results showed that Fe-doped TiO2 nanoparticles effectively degrade MO under Vis-L excitation and follow pseudo-first order kinetics. Besides, kinetic comparison showed that pure TiO2 is less efficient than 0.1% and 0.2% Fe-doped TiO2 because they exhibit unequaled efficiency. Moreover, the photocatalyst at 0.2% Fe-doped TiO2 molar ratio revealed the highest photocatalytic efficiency, which was 4.2 times higher compared to pure TiO2. Different amounts of Fe induced different increases in the apparent first-order rate constant of the photocatalytic process

Experimental investigation of the performance of piezoelectric actuators in a cochlea test rig

Goal: Within the field of hearing prostheses several different devices are available which are applied depending on the kind and severity of hearing deficits experienced by the individual patient. For patients with residual hearing the combination of a hearing aid with a cochlea implant (EAS - electric acoustic stimulation) results in the best quality of hearing perception. In order to optimize EAS, ongoing research focusses on the integration of these stimuli in a single device. Methods: Different inner ear actuator concepts were analyzed before yielding piezoelectric bimorphs as the most feasible one for basilar membrane (BM) stimulation from within the scala tympani. For the experimental validation of the numerical results presented previously, the actuator performance in the cochlea test rig was evaluated.Results and outlook: The experimental analysis for different stimulation frequencies and different locations shows two local BM oscillation peaks, one at the actuator position and one according to the tonotopic cochlea map. Thus confirming our previously presented numerical findings that non-resonant stimulation induces two local BM oscillation maxima, allowing one to stimulate even at those positions where no actuator is present. These results are the border stone for further experimental analysis with multiple actuators as well as miniaturization of mechanical actuators for integration into CI electrodes.Unterstützt durch: This work is supported by the Deutsche Forschungsgemeinschaft (DFG) within the Cluster of Excellence Hearing4allDer Erstautor gibt keinen Interessenkonflikt an

Investigation of intracochlear dual actuator stimulation in a scaled test rig

For patients suffering from profound hearing loss or deafness still having respectable residual hearing in the low frequency range, the combination of a hearing aid with a cochlear implant results in the best quality of hearing perception (EAS – electric acoustic stimulation). In order to optimize EAS, ongoing research focusses on the integration of these stimuli in a single implant device. Within this study, the performance of piezoelectric actuators, particularly the dual actuator stimulation, in a scaled uncoiled test rig was investigated

Investigation of intracochlear dual actuator stimulation in a scaled test rig

For patients suffering from profound hearing loss or deafness still having respectable residual hearing in the low frequency range, the combination of a hearing aid with a cochlear implant results in the best quality of hearing perception (EAS – electric acoustic stimulation). In order to optimize EAS, ongoing research focusses on the integration of these stimuli in a single implant device. Within this study, the performance of piezoelectric actuators, particularly the dual actuator stimulation, in a scaled uncoiled test rig was investigated