Strategies against nonsense: oxadiazoles as translational readthrough-inducing drugs (TRIDs)

This review focuses on the use of oxadiazoles as translational readthrough-inducing drugs (TRIDs) to rescue the functional full-length protein expression in mendelian genetic diseases caused by nonsense mutations. These mutations in specific genes generate premature termination codons (PTCs) responsible for the translation of truncated proteins. After a brief introduction on nonsense mutations and their pathological effects, the features of various classes of TRIDs will be described discussing differences or similarities in their mechanisms of action. Strategies to correct the PTCs will be presented, particularly focusing on a new class of Ataluren-like oxadiazole derivatives in comparison to aminoglycosides. Additionally, recent results on the efficiency of new candidate TRIDs in restoring the production of the cystic fibrosis transmembrane regulator (CFTR) protein will be presented. Finally, a prospectus on complementary strategies to enhance the effect of TRIDs will be illustrated together with a conclusive paragraph about perspectives, opportunities, and caveats in developing small molecules as TRIDs

Aerosol optical properties at Lampedusa (Central Mediterranean) ? 2. Determination of single scattering albedo at two wavelengths for different aerosol types

International audienceAerosol optical properties were retrieved from direct and diffuse spectral irradiance measurements made by a multi-filter rotating shadowband radiometer (MFRSR) at the island of Lampedusa (35.5° N, 12.6° E), in the Central Mediterranean, in the period July 2001?September 2003. In a companion paper (Pace et al., 2005) the aerosol optical depth (AOD) and Ångström exponent were used together with airmass backward trajectories to identify and classify different aerosol types. The MFRSR diffuse-to-direct ratio (DDR) at 415.6 nm and 868.7 nm for aerosol classified as biomass burning-urban/industrial, originating primarily from the European continent, and desert dust, originating from the Sahara, is used in this study to estimate the aerosol single scattering albedo (SSA). A detailed radiative transfer model is initialized with the measured aerosol optical depth; calculations are performed at the two wavelengths varying the SSA values until the modelled DDR matches the MFRSR observations. Sensitivity studies are performed to estimate how uncertainties on AOD, DDR, asymmetry factor (g), and surface albedo influence the retrieved SSA values. The results show that a 3% variation of AOD or DDR produce a change of about 0.02 in the retrieved SSA value at 415.6 and 868.7 nm; a ±0.06 variation of the asymmetry factor g produces a change of the estimated SSA of <0.04 at 415.6 nm, and <0.06 at 868.7 nm; finally, an increase of the assumed surface albedo of 0.05 gives very small changes (0.01?0.02) in the retrieved SSA. The calculations show that the SSA of desert dust (DD) increases with wavelength, from 0.81±0.05 at 415.6 nm to 0.94±0.05 at 868.7 nm; on the contrary, the SSA of urban/industrial (UN) aerosols decreases from 0.96±0.02 at 415.6 nm to 0.87±0.07 at 868.7 nm; the SSA of biomass burning (BB) particles is 0.82±0.04 at 415.6 nm and 0.80±0.05 at 868.7 nm. Episodes of UN aerosols occur usually in June and July; BB aerosol episodes with large AOD and long duration are observed mainly in July and August, the driest months of the year, when the development of fires is favoured

Can alexithymia be assessed through an interview in adolescents? The Toronto Structured Interview for Alexithymia: Reliability, concurrent validity, discriminant validity, and relationships with emotional-behavioral symptoms

Alexithymia is connected to adolescents' psychopathology, but the current methods of assessment present limitations. The Toronto Structured Interview for Alexithymia (TSIA) was developed to overcome the limits of the main used self-rating scale in adults, but no studies investigated its feasibility with adolescents. This study involved 95 community adolescents aged 12-19 years. Adolescents were assessed with the TSIA, the 20-item Toronto Alexithymia Scale (TAS-20), the Verbal Comprehension Index of the WISC-IV for verbal skills, and the Child Behavior Checklist and Youth Self Report for emotional-behavioral symptoms. The aims were to investigate the TSIA internal consistency, concurrent validity with the TAS-20, discriminant validity with participants' verbal skills, and relationships with emotional-behavioral symptoms. TSIA showed good internal consistency, concurrent validity with the TAS-20 (except for factor DDF), and independence by participants' verbal skills, but few relationships with emotional-behavioral symptoms. In conclusion, TSIA showed some good psychometric proprieties but little convergence with research findings obtained with the TAS-20, suggesting the need for further research to check the feasibility of using the TSIA with adolescents. Meanwhile, a precautionary multi-method assessment of alexithymia is recommended

EChO Payload electronics architecture and SW design

EChO is a three-modules (VNIR, SWIR, MWIR), highly integrated spectrometer, covering the wavelength range from 0.55 $\mu$m, to 11.0 $\mu$m. The baseline design includes the goal wavelength extension to 0.4 $\mu$m while an optional LWIR module extends the range to the goal wavelength of 16.0 $\mu$m. An Instrument Control Unit (ICU) is foreseen as the main electronic subsystem interfacing the spacecraft and collecting data from all the payload spectrometers modules. ICU is in charge of two main tasks: the overall payload control (Instrument Control Function) and the housekeepings and scientific data digital processing (Data Processing Function), including the lossless compression prior to store the science data to the Solid State Mass Memory of the Spacecraft. These two main tasks are accomplished thanks to the Payload On Board Software (P-OBSW) running on the ICU CPUs.Comment: Experimental Astronomy - EChO Special Issue 201

Chromosome 5 allelic losses are early events in tumours of the papilla of Vater and occur at sites similar to those of gastric cancer.

During our studies of DNA fingerprinting of tumours of the pancreas and papilla (ampulla) of Vater, using arbitrarily primed polymerase chain reaction (AP-PCR), we noticed two bands showing a decreased intensity in six of ten ampullary tumours with respect to matched normal tissues. Those bands were both assigned to chromosome 5. Such a finding was somewhat in contrast with the reportedly low frequency of APC gene mutations in ampullary cancers, located at chromosome 5q21, and suggested that loci different from that of APC might be the target of chromosome 5 allelic losses (LOH) in these tumours. Therefore, we analysed chromosome 5 LOH in a panel of 27 ampullary tumours, including eight adenomas, four early- and 15 advanced-stage cancers, using 16 PCR-amplified CA microsatellite polymorphic markers spanning the entire chromosome. Nineteen cases (70%) showed LOH, and the interstitial deletions found in these tumours described two smallest common deleted regions, in which putative suppressor genes might reside. They were at 5q13.3-q14 and at 5q23-q31 respectively, which correspond to those found in gastric tumours. In addition, the presence of 5q LOH in six of eight adenomas and in three of four early-stage cancers suggests that such phenomena occur at early stages of neoplastic progression of the ampullary epithelium

Aerosol optical properties at Lampedusa (Central Mediterranean). 1. Influence of transport and identification of different aerosol types

Aerosol optical depth and &#197;ngstr&#246;m exponent were obtained from multi filter rotating shadowband radiometer (MFRSR) observations carried out at the island of Lampedusa, in the Central Mediterranean, in the period July 2001&ndash;September 2003. The average aerosol optical depth at 495.7 nm, &tau;, is 0.24&plusmn;0.14; the average &#197;ngstr&#246;m exponent, &alpha;, is 0.86&plusmn;0.63. The observed values of &tau; range from 0.03 to 1.13, and the values of &alpha; vary from &minus;0.32 to 2.05, indicating a large variability in aerosol content and size. In cloud-free conditions, 36% of the airmasses come from Africa, 25% from Central-Eastern Europe, and 19% from Western France, Spain and the North Atlantic. In summer, 42% of the airmasses is of African origin. In almost all cases African aerosols display high values of &tau; and low values of &alpha;, typical of Saharan dust (average values of &tau; and &alpha; are 0.36 and 0.42, respectively). Particles originating from Central-Eastern Europe show relatively large average values of &tau; and &alpha; (0.23 and 1.5, respectively), while particles from Western France, Spain and the North Atlantic show the lowest average values of &tau; (0.15), and relatively small values of &alpha; (0.92). Intermediate values of &alpha; are often connected with relatively fast changes of the airmass originating sector, suggesting the contemporary presence of different types of particles in the air column. Clean marine conditions are rare at Lampedusa, and are generally associated with subsidence of the airmasses reaching the island. Average values of &tau; and &alpha; for clean marine conditions are 0.11 and 0.86, respectively. The largest values of &alpha; (about 2) were observed in August 2003, when large scale forest fires in Southern Europe produced consistent amounts of fine combustion particles, that were transported to the Central Mediterranean by a persistent high pressure system over Central Europe. Smoke particles in some cases mix with desert dust, producing intermediate values of &alpha;. The seasonal distribution of the meteorological patterns over the Mediterranean, the efficiency of the aerosol production mechanisms, and the variability of the particles' residence time produce a distinct seasonal cycle of aerosol optical depths and &#197;ngstr&#246;m exponent values. Particles originating from all sectors show a summer maximum in aerosol optical depth. The summer increase in optical depth for European aerosols is linked with an increment in the values of &alpha;, that indicates an enhancement in the number of fine particles. The summer maximum of &tau; for African particles is associated with a weak reduction in the &#197;ngstr&#246;m exponent, suggesting an increase in the total number of particles and a relatively more intense transport of large particles. The observations were classified according to the aerosol optical properties, and two main classes have been identified: desert dust and biomass burning/urban-industrial aerosols. Values of &tau; and &alpha; averaged over the whole observing period are 0.37 and 0.15 for desert dust, and 0.27 and 1.77 for urban-industrial/biomass burning aerosols

Ileocecal duplication cysts: Is the loss of the valve always necessary?

Ileocecal (IC) duplication cysts are enteric duplications located at the IC junction, not clearly identified in all the published series. The reported treatment is IC resection and ileocolic anastomosis. It is well known that the loss of the IC valve has several adverse effects. This study is aimed at demonstrating that cyst removal together with the common ileal wall and following enterorrhapy is possible, safe, and effective in preserving the IC region. Methods Medical records of 3 patients who underwent surgery for IC duplication between 2003 and 2013 were retrospectively reviewed evaluating follow-up results. Results All patients had an antenatal diagnosis of intrabdominal cystic mass. In two cases associated malformations were reported. The lesions presented at newborn age with intermittent small bowel obstruction and required removal. No patients underwent IC resection. The diagnosis of duplication cyst was confirmed by histo-pathologic examination. The postoperative course was uneventful, even in the long-term follow-up

The Visible and Near Infrared module of EChO

The Visible and Near Infrared (VNIR) is one of the modules of EChO, the Exoplanets Characterization Observatory proposed to ESA for an M-class mission. EChO is aimed to observe planets while transiting by their suns. Then the instrument had to be designed to assure a high efficiency over the whole spectral range. In fact, it has to be able to observe stars with an apparent magnitude Mv= 9-12 and to see contrasts of the order of 10-4 - 10-5 necessary to reveal the characteristics of the atmospheres of the exoplanets under investigation. VNIR is a spectrometer in a cross-dispersed configuration, covering the 0.4-2.5 micron spectral range with a resolving power of about 330 and a field of view of 2 arcsec. It is functionally split into two channels respectively working in the 0.4-1 and 1.0-2.5 micron spectral ranges. Such a solution is imposed by the fact the light at short wavelengths has to be shared with the EChO Fine Guiding System (FGS) devoted to the pointing of the stars under observation. The spectrometer makes use of a HgCdTe detector of 512 by 512 pixels, 18 micron pitch and working at a temperature of 45K as the entire VNIR optical bench. The instrument has been interfaced to the telescope optics by two optical fibers, one per channel, to assure an easier coupling and an easier colocation of the instrument inside the EChO optical bench.Comment: 26 page