The GCC repeat length in the 5'UTR of MRP1 gene is polymorphic: a functional characterization of its relevance for cystic fibrosis

BACKGROUND: Among the members of the ATP binding cassette transporter superfamily, MRPs share the closest homology with the CFTR protein, which is defective in CF disease. MRP1 has been proposed as a potential modifier gene and/or as novel target for pharmacotherapy of CF to explain the clinical benefits observed in some CF patients treated with the macrolide AZM. The 5'UTR of the MRP1 gene contains a GCC triplet repeat that could represent a polymorphic site and affect the activity of the promoter. METHODS: The MRP1 5' flanking region was amplified by PCR from 36 CF patients and 100 non-CF subjects and the number of GCC triplets of each allele was determined by sequence and electrophoretic analysis. We performed gene reporter studies in CF airway epithelial cells 16HBE14o-AS3, in basal conditions and in the presence of AZM. RESULTS: We found that the GCC repeat is polymorphic, ranging from 7 to 14 triplets either in CF or in non-CF subjects. Our data are preliminary and have to be confirmed on a larger population of CF subjects. The transcriptional activity of the proximal MRP1 5' regulatory region revealed no statistically significant correlations between the number of repeats and treatment with AZM. CONCLUSION: We identified a novel polymorphism in the 5'UTR of MRP1 gene that provides multiple alleles in a gene relevant for multidrug resistance as well as for CF, determining that this region is transcriptionally active and that this activity does not appear to be influenced by AZM treatment

From InSb Nanowires to Nanocubes: Looking for the Sweet Spot

High aspect ratios are highly desired to fully exploit the one-dimensional properties of indium antimonide nanowires. Here we systematically investigate the growth mechanisms and find parameters leading to long and thin nanowires. Variation of the V/III ratio and the nanowire density are found to have the same influence on the “local” growth conditions and can control the InSb shape from thin nanowires to nanocubes. We propose that the V/III ratio controls the droplet composition and the radial growth rate and these parameters determine the nanowire shape. A sweet spot is found for nanowire interdistances around 500 nm leading to aspect ratios up to 35. High electron mobilities up to 3.5 × 10^4 cm^2 V^(–1) s^(–1) enable the realization of complex spintronic and topological devices

O+ heating associated with strong activity in the high altitude cusp and mantle

We use the Cluster spacecraft to study three events with intense waves and energetic oxygen ions (O+) in the high altitude cusp and mantle. The ion energies considered are of the order 1000 eV and higher, observed above an altitude of 8 earth radii together with high wave power at the O+ gyrofrequency. We show that heating by waves can explain the observed high perpendicular energy of O+ ions, using a simple gyroresonance model and 25–45% of the observed wave spectral density at the gyrofrequency. This is in contrast to a recently published study where the wave intensity was too low to explain the observed high altitude ion energies. Long lasting cases (>10 min) of high perpendicular-to-parallel temperature ratios are sometimes associated with low wave activity, suggesting that high perpendicular-to-parallel temperature ratio is not a good indicator of local heating. Using multiple spacecraft, we show that the regions of enhanced wave activity are at least one order of magnitude larger than the gyroradius of the heated ions

Statistical evidence for O⁺ energization and outflow caused by wave-particle interaction in the high altitude cusp and mantle

We present a statistical study of the low (<1 Hz) frequency electric and magnetic field spectral densities observed by Cluster spacecraft in the high altitude cusp and mantle region. At the O+ gyrofrequency (0.02–0.5 Hz) for this region the electric field spectral density is on average 0.2–2.2 (mV m−1)2 Hz−1, implying that resonant heating at the gyrofrequency can be intense enough to explain the observed O+ energies of 20–1400 eV. The relation between the electric and magnetic field spectral densities results in a large span of phase velocities, from a few hundred km s−1 up to a few thousand km s−1. In spite of the large span of phase velocity, the ratio between the calculated local Alfvén velocity and the estimated phase velocity is close to unity. We provide average values of a coefficient describing diffusion in ion velocity space at different altitudes, which can be used in studies of ion energization and outflow. The observed average waves can explain the average O+ energies measured in the high altitude (8–15 RE) cusp/mantle region of the terrestrial magnetosphere according to our test particle calculations

Stationery injuries in the upper aerodigestive system: results from the Susy Safe Project.

Rationale and aim: Foreign body (FB) injuries are a relatively frequent event in young children. Clinical picture can be evidently affected from different variables. Among those size, shape, type and FB location cover an important issue. Increased attempts have been made in order to encourage normative interventions for products devoted to children's care and entertainment, reaching acceptable safety level; on the contrary, fewer efforts have been devoted to investigate the risk associated to objects that - even if not expressly created for children - are easy accessed by children, like stationery.The aim of the present study is to characterize the risk of complications and prolonged hospitalization due to stationery items according to age and gender of patients, FB characteristics and FB location, circumstances of the accident, as emerging from the Susy Safe Registry. Methods: From 2005 to 2010 case were collected from 70 centers in 32 different countries. Details on the injuries, identified by means of the International Classification of Diseases, Ninth Revision (ICD-9) codes listed on hospital discharge records, were gathered through a standardized case report form, that provides a full set of information on injuries, with specific details on age and gender of the child, location, shape, volume, consistency and ellipticity of the foreign body, behavioral aspects linked to the injury, like the supervision of the parents or the activity concomitant to the accident, any complication occurred, length of hospitalization. Results: In the years 2005-2010 a total of 17,205 FB injuries in children aged 0-14. years were registered in Susy Safe Database. Among them 425 (2.5%) were due to a stationery item. The majority of FBs were retrieved in the nose (179, meaning 42.1%) and in the ears (176, 41.4%) only 5 cases were observed in children younger than 1. year, while most of the cases, 80.6%, were recorded in children older than 3. years. 193 patients (45.4%) were female, while 232 (54.6%) were male. Adult supervision was indicated in 212 cases. In 143 of these accidents the adult was present (33.6% of the whole group). The most frequent stationery retrieved was rubber, counting for 209 cases (49.2%). According to the FBs types, mostly all cases reported a 3D volume and a rigid or semirigid consistency (49.3%). Looking to the outcomes, 31 (7%) children needed hospitalization and complications were seen in 38 children (8.9%). No significant associations were seen between the outcomes and the FBs' characteristics, excluded those between the consistency of the FB (rigid) and the necessity of hospitalization and the shape (2D) and the presence of complication. Conclusions: Injuries are events that in many cases can be prevented with appropriate strategies. Passive environmental strategies, including product modification by manufacturers, are the most effective. However, regulation regarding small parts of potentially dangerous objects covers products addressed to children use but objects not projected for children, such as stationary items, are excluded. Our study testifies that stationary is involved in a non-negligible percentage of FB injuries, mainly due to insertion in the ears. Frequently, injuries happen under adult supervision. These results confirm the fact that when passive preventive strategies are not practical, active strategies that promote behavior change are necessary and information about this issue should be included in all visits to family pediatricians

Risk posed to children by stationery items in the upper airways.

AIM: The aim of the present study is to characterize the risk of complications and prolonged hospitalization due to stationery items according to age and gender of patients, FB characteristics and foreign body (FB) location, circumstances of the accident, as emerging from the ESFBI study. METHODS: A retrospective study in major hospitals of 19 European countries was realized on children aged 0-14 having inhaled/aspired or ingested a stationery item. In the years 2000-2003 a total of 2094 FB injuries occurred in children aged 0-14 years. The characteristics of the child, the FB consistency and the occurrence of complications were analyzed. RESULTS: Among FB injuries, 62 (3%) were due to a stationery item: 32 were due to objects insertion in the ears while 30 occurred in the upper and lower respiratory tract. Objects most frequently involved are parts of pens in children younger than 3 years and eraser in older. 39% of children needed hospitalization. The most documented complication was inflammation of external ear. Almost 24% of injuries happened under adults' supervision. CONCLUSION: Injuries are events that in many cases can be prevented with appropriate strategies. Passive environmental strategies, including product modification by manufacturers, are the most effective. Our study testifies that stationary is involved in a non negligible percentage of FB injuries. This results confirm the fact that when passive preventive strategies are not practical, active strategies that promote behaviour change are necessary and information about this issue should be included in all visits to family pediatricians