2,451 research outputs found
Toward the De novo Design of a Catalytically Active Helix-Bundle: a Substrate Accessible Carboxylate-bridged Dinuclear Metal Center
No full textDe novo design of proteins provides an attractive approach to uncover the essential features required for their functions. Previously, we described the design and crystal structure determination of a di-Zn(II) complex of “due-ferri-1” (DF1), a protein patterned after the diiron−dimanganese class of redox-active proteins [Lombardi, A.; Summa, C.; Geremia, S.; Randaccio, L.; Pavone, V.; DeGrado, W. F. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 6298−6305]. The overall structure of DF1, which contains a carboxylate-bridged dinuclear metal site, agrees well with the intended design. However, access to this dimetal site is blocked by a pair of hydrophobic leucine residues (L13 and L13‘), which prevent facile entry of metal ions and small molecules. We have now taken the next step in the eventual construction of a catalytically active metalloenzyme by engineering an active site cavity into DF1 through the replacement of these two leucine residues with smaller residues. The crystal structure of the dimanganous form of L13A-DF1 indeed shows a substrate access channel to the dimetal center. In the crystal structure, water molecules and a ligating dimethyl sulfoxide molecule, which forms a monatomic bridge between the metal ions, occupy the cavity. Furthermore, the diferric form of a derivative of L13A-DF1, DF2, is shown to bind azide, acetate, and small aromatic molecules
Neonatal Autoimmune Hypothyroidism: a patient report
No full textBackground: Acquired primary hypothyroidism in neonates and infants under 3 years of age is very rare. Herein we report the case of an infant female affected by acquired autoimmune hypothyroidism.
Patient report: The infant was transferred to the Pediatric Clinic, University of Catania, Italy for evaluation of dysmorphic features, growth and motor retardation, and hypothyroidism on laboratory testing. Neonatal screening test for TSH and PKU was negative. An ultrasound scan showed a non-homogeneous thyroid gland which was increased in volume. Based on the laboratory results, the diagnosis of autoimmune hypothyroidism was made and L-thyroxine treatment was initiated at 50 microg/day.
Conclusions: Autoimmune hypothyroidism in infancy is rare, but early recognition and therapy are essential to prevent neurologic damage and growth deficits. In this patient we would like to underline the early age of appearance of autoimmune thyroid disease and the possible onset of pathologic events before birth
Meet the expert 3: L’ Ortopedia e Traumatologia pediatrica sta cambiando? Progressi dell’ultimo decennio. Speaker: F. Canavese. Casi clinici. Discussore: V. Pavone
No full textGradient Descent-Based Task-Orientation Robot Control Enhanced With Gaussian Process Predictions
No full textThis letter proposes a novel force-based task-orientation controller for interaction tasks with environmental orientation uncertainties. The main aim of the controller is to align the robot tool along the main task direction (e.g., along screwing, insertion, polishing, etc.) without the use of any external sensors (e.g., vision systems), relying only on end-effector wrench measurements/estimations. We propose a gradient descent-based orientation controller, enhancing its performance with the orientation predictions provided by a Gaussian Process model. Derivation of the controller is presented, together with simulation results (considering a probing task) and experimental results involving various re-orientation scenarios, i.e., i) a task with the robot in interaction with a soft environment, ii) a task with the robot in interaction with a stiff and inclined environment, and iii) a task to enable the assembly of a gear into its shaft. The proposed controller is compared against a state-of-the-art approach, highlighting its ability to re-orient the robot tool even in complex tasks (where the state-of-the-art method fails)
Viscosity in isotropic cosmological backgrounds in general relativity and Starobinsky gravity
No full textWe present a general analysis of the role of shear viscosity in cosmological backgrounds, focusing on isotropic space-time in both Einstein and f(R) gravity. By computing the divergence of the stress-energy tensor in a general class of isotropic (but not necessarily homogeneous) geometries, we show that shear viscosity does not contribute to the background dynamics when the fluid is comoving. This result holds in both the Jordan and Einstein frames, and implies that shear viscosity cannot affect the electromagnetic luminosity distance which is determined by the background light-like geodesics.As an application of our results, we critically examine recent claims that shear viscosity can alter the Hubble evolution and the electromagnetic luminosity distance in Starobinsky gravity. We demonstrate that the continuity equation used in that work is at odds both with the covariant conservation of the stress-energy tensor and the local second law of thermodynamics. We further show that even in models where such modifications could mimic bulk viscosity, the resulting entropy evolution is inconsistent with standard thermodynamic expectations
Cutaneous and leptomeningeal hemangiomas with impressive benign evolution
No full textWe describe an infant with cutaneous and leptomeningeal diffuse hemangiomata. Clinical facial anomalies were evident at birth. Routine transfontanellar ultrasonography revealed very diffuse leptomeningeal hemangioma. Magnetic resonance imaging during the first days of age confirmed vascular lesions. The patient was otherwise normal, and was monitored at ages 3.5, 9, and 18 months. Rapid resolution of the hemangioma occurred within 1 year. The infant did not present with persistent embryonic arteries, a posterior fossa, or other malformations typically reported in Pascual-Castroviejo type II syndrome. However, the characteristic skin color, leptomeningeal hemangioma, and rapid involution prompted the diagnosis of Pascual-Castroviejo II syndrome in its wider, benign spectrum
Lissencephalic syndromes: brain and beyond
No full textLissencephaly has been long maintained a malformation involving only the brain. Classic lissencephaly includes agyria and pachygyria and it is the most severe form of malformations derived from abnormal neuronal migration. It is defined as a smooth or nearly smooth cerebral surface with absence of normal sulci and gyria. It encompasses a group of syndromes which show many different clinical conditions. Four groups are actually distinguished: classic lissencephaly variants, other lissencephalies including forms with unknown pathogenesis, microlissencephaly spectrum and Cobblestone cortical malformations. Several genes and proteins are involved in this syndromic spectrum and each year new molecular data are reported in the literature: classifications in this sense are always in progress. Lissencephaly now is recognised to involve not only the brain but also several other organs and districts including eyes, face, muscles, genital organs, heart and bones. Mental retardation and different form of epilepsies usually drug-resistant are the main clinical signs. The Authors in this topic discuss on this subject, underlying the different forms of lissencephaly their wide heterogeneity and the complex involvement of several organ
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