Istituto Italiano di Tecnologia

About: Istituto Italiano di Tecnologia is a facility organization based out in Genoa, Italy. It is known for research contribution in the topics: Humanoid robot & Robot. The organization has 4561 authors who have published 14595 publications receiving 437558 citations. The organization is also known as: Italian Institute of Technology & IIT.

High-performance and site-directed in utero electroporation by a triple-electrode probe

Abstract: In utero electroporation is a powerful tool to transfect and manipulate neural-precursor cells of the rodent parietal cortex and their progeny in vivo. Although this technique can potentially target numerous brain areas, reliability of transfection in some brain regions is low or physical access is limited. Here we present a new in utero electroporation configuration based on the use of three electrodes, the relative position and polarities of which can be adjusted. The technique allows easy access and exceedingly reliable monolateral or bilateral transfection at brain locations that could only be sporadically targeted before. By improvement in the efficiency of the electrical field distribution, demonstrated here by a mathematical simulation, the multi-electrode configuration also extends the developmental timeframe for reliable in utero electroporation, allowing for the first time specific transfection of Purkinje cells in the rat cerebellum.

A large genomic deletion leads to enhancer adoption by the lamin B1 gene: a second path to autosomal dominant adult-onset demyelinating leukodystrophy (ADLD)

Abstract: Chromosomal rearrangements with duplication of the lamin B1 (LMNB1) gene underlie autosomal dominant adult-onset demyelinating leukodystrophy (ADLD), a rare neurological disorder in which overexpression of LMNB1 causes progressive central nervous system demyelination. However, we previously reported an ADLD family (ADLD-1-TO) without evidence of duplication or other mutation in LMNB1 despite linkage to the LMNB1 locus and lamin B1 overexpression. By custom array-CGH, we further investigated this family and report here that patients carry a large (∼660 kb) heterozygous deletion that begins 66 kb upstream of the LMNB1 promoter. Lamin B1 overexpression was confirmed in further ADLD-1-TO tissues and in a postmortem brain sample, where lamin B1 was increased in the frontal lobe. Through parallel studies, we investigated both loss of genetic material and chromosomal rearrangement as possible causes of LMNB1 overexpression, and found that ADLD-1-TO plausibly results from an enhancer adoption mechanism. The deletion eliminates a genome topological domain boundary, allowing normally forbidden interactions between at least three forebrain-directed enhancers and the LMNB1 promoter, in line with the observed mainly cerebral localization of lamin B1 overexpression and myelin degeneration. This second route to LMNB1 overexpression and ADLD is a new example of the relevance of regulatory landscape modifications in determining Mendelian phenotypes.

The influence of catalysis on mad2 activation dynamics.

Abstract: Mad2 is a key component of the spindle assembly checkpoint, a safety device ensuring faithful sister chromatid separation in mitosis. The target of Mad2 is Cdc20, an activator of the anaphase-promoting complex/cyclosome (APC/C). Mad2 binding to Cdc20 is a complex reaction that entails the conformational conversion of Mad2 from an open (O-Mad2) to a closed (C-Mad2) conformer. Previously, it has been hypothesized that the conversion of O-Mad2 is accelerated by its conformational dimerization with C-Mad2. This hypothesis, known as the Mad2-template hypothesis, is based on the unproven assumption that the natural conversion of O-Mad2 required to bind Cdc20 is slow. Here, we provide evidence for this fundamental assumption and demonstrate that conformational dimerization of Mad2 accelerates the rate of Mad2 binding to Cdc20. On the basis of our measurements, we developed a set of rate equations that deliver excellent predictions of experimental binding curves under a variety of different conditions. Our results strongly suggest that the interaction of Mad2 with Cdc20 is rate limiting for activation of the spindle checkpoint. Conformational dimerization of Mad2 is essential to accelerate Cdc20 binding, but it does not modify the equilibrium of the Mad2:Cdc20 interaction, i.e., it is purely catalytic. These results surpass previously formulated objections to the Mad2-template model and predict that the release of Mad2 from Cdc20 is an energy-driven process.

Propeller-based wireless device for active capsular endoscopy in the gastric district.

Abstract: An innovative approach to active locomotion for capsular endoscopy in the gastric district is reported in this paper. Taking advantage of the ingestion of 500 ml of transparent liquid by the patient, an effective distension of the stomach is safely achieved for a timeframe of approximately 30 minutes. Given such a scenario, an active swallowable capsule able to navigate inside the stomach thanks to a four propeller system has been developed. The capsule is 15 mm in diameter and 30 mm in length, and it is composed of a supporting shell containing a wireless microcontroller, a battery and four motors. The motors enable the rotation of propellers located in the rear side of the device, thus obtaining a reliable locomotion and steering of the capsule in all directions in a liquid. The power consumption has been properly optimized in order to achieve an operative lifetime consistent with the time of the diagnostic inspection of the gastric district, assumed to be no more than 30 minutes. The capsule can be eas...

Accurate Anharmonic Vibrational Frequencies for Uracil: The Performance of Composite Schemes and Hybrid CC/DFT Model

Abstract: The vibrational spectrum (frequencies as well as intensities) of uracil has been investigated at a high level of theory. The harmonic force field has been evaluated at the coupled-cluster (CC) level in conjunction with a triple-ζ basis set. Extrapolation to the basis set limit as well as inclusion of core-correlation and diffuse-function corrections have been considered by means of the second-order Moller-Plesset perturbation theory. To go beyond the harmonic approximation, a hybrid CC/DFT approach has been employed, which will be proved to provide state-of-the-art results. As the spectroscopic investigation of uracil is hampered by numerous Fermi resonances, models for explicitly taking them into account have been implemented and applied. On general grounds, the computational procedure presented is able to provide the proper accuracy to support experimental investigations of large molecules of biological interest.